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Sediaan Farmasi: "SIROP"

SIROP
(Sirupi)

Oleh:
OKTAFIAN V.F. Kawulusan

A. Sejarah & Pengertian Sirop


Sirop telah dikenal sebagai bentuk sediaan obat sejak masa Arab kuno yang dikenalkan
oleh Avicenna (Ali Ibnu Sina), ahli farmasi berkembangsaan Arab. Istilah Sirop diduga berasal
dari kara Sirab (Bah. Arab), yang artinya adalah sari pati gula. Berikut ini, beberapa definisi
tentang sirop:
Sirop adalah sediaan pekat dalam air dari gula atau pengganti gula dengan atau tanpa
penambahan bahan pewangi dan zat obat (Ansel, 1989).
Sirop adalah sediaan cairan kental mengandung sukrose (gula) tidak kurang dari 50% dan tidak
lebih dari 65%, dapat mengandung satu atau lebih bahan obat (Priyambodo, 2007).
Sirop adalah bentuk sediaan cair yang mengandungSaccharosa atau gula. Konsistensi sirup
kental karena kadar Saccharosa yang tinggi, yaitu 64,0-66,0% (Zaman-Joenoes, 2008).
Sirop adalah sediaan cair berupa larutan yang mengandung sakarosa. Kecuali dinyatakan lain,
kadar sakarosa, C12H22O11, tidak kurang dari 64.0% dan tidak lebih dari 66,0%.
B. Penggolongan Sirop
Bedasarkan fungsinya, sirop dikelompokan menjadi 2 golongan, yaitu:
1. Medicated Syrup (sirop obat) merupakan sirup yang mengandung satu atau lebih bahan obat.
Sirop obat berupa preparat yang sudah distandarisasi, dapat diberikan berupa obat tunggal
atau dikombinasikan dengan obat lain. Contoh sirop obat antara lain:

a. Sirop sebagai ekspektorans:


Sirop Thymi.
Sirop Thymi et Serpylli = Sirop Thymi Compositus.
Sirop Althae.
b. Sirop sebagai antitusif:
Sirop Codeini, mengandung 2 mg Codein/ml sirop.
c. Sirop sebagai anthelmintik:
Sirop Piperazini, mengandung 1 g Piperazine dalam bentuk hexahydrat/citrat dalam tiap 5 ml
sirop.
d. Sirop sebagai antibiotik
Sirop Kanamycin, mengandung 50 mg/ml.
Sirop Chloramphenicol, umumnya mengandung 25 mg/ml.
Sirop Ampicillin, umumnya mengandung 25 mg/ml.
Sirop Amoxycillin, umumnya mengandung 25 mg/ml.
Sirop Cloxacillin, umumnya mengandung 25 mg/ml.
e. Dry Syrup atau sirop kering, berupa campuran obat dengan sakarosa, harus dilarutkan dalam
jumlah air tertentu sebelum dipergunakan. Keuntungan sirop kering dari pada sirop cairan,
biasanya sirop kering dapat tahan disimpan lebih lama. Contohnya Ampicillin trihydrate dry
syrup, ekivalen dengan 25 mg/ml sirop cairan kalau sudah dilarutkan dalam jumlah air yang
ditentukan.
2. Flavored Syrup (sirop korigen/pembawa), biasanya tidak digunakan untuk tujuan medis, namun
mengandung berbagai bahan aromatis atau rasa yang enak dan digunakan sebagai larutan
pembawa atau pemberi rasa pada berbagai sediaan farmasi lainnya, misalnya sebagai penutup
rasa pahit pada Vitamin B Kompleks yang diberikan kepada bayi atau anak-anak. Sirop
golongan ini, mengandung berbagai bahan tambahan, misalnya bahan antioksidan (antioxidant
agent), pengawet (preservative agent), pewarna (coloring agent), pemberi rasa (flavoring

agent), dan bahan pelarut (diluting agent). Sirop ini, ditambahkan sebagai korigens rasa untuk
obat minum, cukup dalam jumlah 10-20 ml untuk tiap 100 ml larutan obat. Sirop yang sering
dipakai sebagai korigens-rasa, yaitu:
a. Sirop Simpleks, mengandung 65% gula dalam larutan nipagin 0,25% b/v.
b. Sirop Aurantii, terutama untuk bahan obat yang rasanya pahit.
c. Sirop Rubi Idaei, terutama untuk bahan obat yang rasanya asam.
C. Formula & Pembuatan Sirop
Sebagian besar sirop mengandung komponen-komponen berikut disamping air murni
(purified water) dan semua zat-zat obat yang ada:
Gula, biasanya sukrosa atau pengganti gula yang digunakan untuk memberi rasa manis dan
kental.
Pengawet antimikroba.
Pembau.
Pewarna.
Juga banyak sirop, terutama yang dibuat dalam perdagangan, mengandung pelarut-pelarut
khusus, pembantu kelarutan, pengental dan stabilisator.
Menurut Farmakope Indonesia edisi III (1979), kecuali dinyatakan lain, sirop dibuat
sebagai berikut:
Buat cairan untuk sirop, panaskan, tambahkan gula, jika perlu didihkan hingga larut. Tambahkan
air mendidih secukupnya hingga diperoleh bobot yang dikehendaki, buang busa yang terjadi,
serkai.
Pada pembuatan sirop dari simplisia yang mengandung glukosida antrakuinon, ditambahkan
natrium karbonat sejumlah 10% bobot simplisia.
Kecuali dinyatakan lain, pada pembuatan sirop simplisia untuk persediaan ditambahkan metil
paraben 0,25% b/v atau pengawet lain yang cocok.

Dalam produksi besar di industri farmasi, pemilihan bahan yang digunakan untuk
pembuatan sediaan sirop harus dilakukan dengan hati-hati, termasuk air yang digunakan juga
harus memenuhi persyaratan air untuk produk farmasi (purified water). Kebersihan wadah dan
alat untuk produksi juga memegang peranan yang sangat penting. Hal lain yang mempengaruhi
proses pembuatan sirop adalah karakteristik bahan baku yang digunakan, peralatan, prosedur
pencampuran dan pengisian ke dalam wadah.
Bahan baku yang digunakan dalam proses pembuatan sediaan sirop harus sesuai
dengan spesifikasi yang telah ditentukan dan ditentukan secara cermat. Spesifikasi tersebut
harus bisa menjamin ciri-ciri, kemurnian, homogenitas, dan bebas dari kontaminasi mikroba
yang berlebihan. Selain bahan aktif, air juga merupakan faktor yang sangat kritis dalam proses
pembuatan sediaan sirop, karena merupakan komponen terbesar.
Peralatan yang digunakan untuk proses pembuatan sediaan sirop terdiri dari tangki
pencampur yang dilengkapi dengan pengaduk berkecepatan tinggi, penyaring, dan pengisi
sirop ke dalam wadah (botol). Tangki, umumnya dibuat dari bahan baja anti-karat AISI 316 yang
dipoles berlapis dua (double jacket), dimana panas dari uap air (steam boiler) yang digunakan
untuk memanaskan sirop dilewatkan diantara kedua dinding tangki. Tangki tersebut bisa ditutup
dengan rapat sehingga lebih efektif.
Proses pembuatan sediaan sirop dapat dilakukan dengan beberapa metode/cara,
tergantung dari bahan yang digunakan, terutama menyangkut sifat-sifat fisik dan kimia dari
bahan aktif. Metode pembuatan sirop tersebut antara lain:
Metode pelarutan dengan pemanasan.
Metode pengadukan tanpa pemanasan.
Metode penambahan bahan aktif ke dalam sirup sederhana (Sirop Simpleks atau Flavoring
Syrup).
Metode perkolasi.
Metode pembuatan sediaan sirop dengan menggunakan pemanasan merupakan
metode yang paling umum digunakan, sangat cocok digunakan untuk bahan-bahan yang tidak
rusak akibat pemanasan serta apabila dikehendaki proses pembuatan sirop secara cepat.

Mula-mula gula (sucrose) dilarutkan di dalam air murni (purified water) yang telah
dipanaskan pada suhu 50-700C sambil diaduk hingga larut. Selanjutnya bahan aktif dan bahan
pengawet dimasukkan ke dalam larutan gula dan diaduk hingga semua bahan larut sempurna,
kemudian didinginkan hingga suhu 300C. Masukkan ke dalam larutan tersebut bahan-bahan
tambahan lain (pengental, pewarna dan perasa), aduk hingga homogen. Saring larutan dengan
penyaring yang sesuai, selanjutnya sirop tersebut dimasukkan ke dalam wadah. (botol) yang
dikehendaki dan dilakukan proses pengemasan. Hal yang sangat penting dalam proses
pembuatan sediaan sirop dengan metode ini adalah suhu jangan sampai terlalu tinggi (>70 0C)
karena akan menyebabkan terjadinya inversin gula menjadi gula inert serta karamelisasi gula
yang di tandai dengan warna sirop menjadi cokelat.
Untuk bahan-bahan yang tidak tahan (rusak) atau menguap apabila dipanaskan, maka
dapat digunakan metode pengadukan tanpa pemanasan, penambahan bahan aktif ke dalam
sirup sederhana atau metode perkolasi.
Pada sirop dengan kadar gula rendah dapat terjadi fermentasi, kadar gula yang tinggi
mempunyai tekanan osmotik yang cukup tinggi sehingga pertumbuhan bakteri dan fungi dapat
terhambat. Bila sebagian dari sakarosa berubah menjadi gula invert, maka sirop cepat menjadi
rusak. Kerusakan sirop dapat dihindarkan dengan menambahkan suatu bahan pengawet ke
dalam sirop, misalnya Nipasol, Nipagin atau Natrium Benzoat.
Selain sukrosa dan gula lain, pada sirop dapat ditambahkan senyawa poliol seperti
sorbitol dan gliserin untuk menghambat penghabluran dan mengubah kelarutan, rasa dan sifat
lain zat pembawa. Umunya juga dalam pembuatan sirop, ditambahkan zat antimikroba untuk
mencegah pertumbuhan bakteri dan fungi.
Penetapan kadar sakarosa dalam sirop menurut Farmakope Indonesia edisi III (1979)
adalah sebagai berikut:
Timbang saksama lebih kurang 25 g sirop dalam labu tentukur 100 ml, tambahkan 50 ml
air dan sedikit larutan aluminium hidroksida P. Tambahkan larutan timbal (III) subasetat P tetes
demi tetes hingga tetes terakhir tidak menimbulkan kekeruhan.
Tambahkan air secukupnya hingga 100 ml, saring, buang 10 ml filtrat pertama.
Masukkan 50,0 ml filtrat ke dalam labu tentukur 55 ml, tambahkan campuran 79 bagian volume
asam klorida P dan 21 bagian volume air secukupnya hingga 55,0 ml. Panaskan labu dalam
tangas air pada suhu antara 680 C dan 700 C selama 10 menit, dinginkan dengan cepat

sehingga suhu lebih kurang 200 C. Jika perlu hilangkan warna menggunakan tidak lebih dari
100 mg arang jerap P. Ukur rotasi optik larutan yang belum diinversi menggunakan tabung 22,0
cm pada suhu pengukur yang sama antara 10 0 C dan 250 C. Hitung kadar dalam % C12H22O11,
dengan rumus:
300x1-2
C= -----------------------(144-0,5t)

Keterangan:
1 adalah rotasi optik larutan yang belum diinversi.
2 adalah rotasi optik larutan yang telah diinversi.
T adalah suhu.

Penyimpanan sirop menurut anjuran Farmakope Indonesia edisi III (1979), dalam wadah
tertutup rapat, di tempat sejuk.

Pustaka:
Ansel HC, 1989.Pengantar Bentuk Sediaan Farmasi. Penerjemah Farida Ibrahim; Pendamping
Asmanizar, Iis Aisyah. Jakarta: Penerbit Universitas Indonesia (UI Press).
Priyambodo B, 2007. Manajemen Farmasi Industri. Yogyakarta: Global Pustaka Utama.
Syamsuni HA, 2006. Ilmu Resep. Jakarta: EGC.
Tim Penyusun Farmakope Indonesia, 1979. Farmakope Indonesia Edisi III. Jakarta: Departemen
Kesehatan Republik Indonesia.
Zaman-Joenoes N, 2008. Ars Prescribendi Resep yang Rasional. Surabaya: Airlangga University
Press.

Tekhnologi Farmasi (Sediaan Sirup)

Sirup adalah salah satu bentuk sediaan cair yang dalam dunia
farmasi yang dikenal luas oleh masyarakat. Saat ini, banyak sediaan sirup yang beredar di
pasaran dari berbagai macam merk, baik yang generic maupun yang paten. Biasanya, orangorang mengunakan sediaan sirup karena disamping mudah penggunaannya, sirup juga
mempunyai rasa yang manis dan aroma yang harum serta warna yang menarik sehingga disukai
oleh berbagai kalangan, terutama anak-anak dan orang yang susah menelan obat dalam bentuk
sediaan oral lainnya.
Sirup didefinisikan sebagai sediaan cair yang mengandung sakarosa. Kecuali dinyatakan
lain, kadar sakarosa tidak kurang dari 64% dan tidak lebiih dari 66%. Secara umum, sirup dibagi
menjadi 2 macam yaitu Non Medicated Syrup/Flavored Vehicle Syrup (Seperti cherry syrup,
cocoa syrup, orange syrup) dan Medicated Syrup/Sirup Obat (Seperti sirup piperazina sitrat,
sirup isoniazid). Non Medicated Sirup adalah sediaan syrup yang tidak mengandung bahan obat,
melainkan hanya mengandung gula, perasa, pengawet dan perwarna sedangkan Sirup Obat
mengandung bahan obat/Zat berkhasiat.

Definisi
Menurut farmakope Indonesia III, sirup adalah sedian cair berupa larutan yang mengandung
sakarosa, C12H22O11, tidak kurang dari 64.0% dan tidak lebih dari 66.0%.
Sirup adalah larutan oral yang mengandung sukrosa atau gula lain dalam kadar tinggi
(Anonim, 1995). Secara umum sirup merupakan larutan pekat dari gula yang ditambah obat atau
zat pewangi dan merupakan larutan jernih berasa manis. Syrup adalah sediaan cair kental yang
minimal mengandung 50% sakarosa (Ansel et al., 2005).

Dalam perkembangannya, banyak sekali pengertian mengenai sirup. Sirup adalah sediaan
cair berupa larutan yang mengandung sakarosa (Anonim, 1979). Sirup adalah sediaan cairan
kental untuk pemakaian dalam, yang minimal mengandung 90% sakarosa (Voigt, 1984).

Penggolongan Sirup
Bedasarkan fungsinya, sirup dikelompokan menjadi 2 golongan, yaitu:
1. Medicated Syrup (sirup obat)
Merupakan sirup yang mengandung satu atau lebih bahan obat. Sirup obat berupa preparat
yang sudah distandarisasi, dapat diberikan berupa obat tunggal atau dikombinasikan dengan obat
lain. Contoh sirup obat antara lain: Sirup sebagai ekspektorans contohnya yaitu Sirup Thymi.
Sirup Thymi et Serpylli = Sirop Thymi Compositus. Sirop Althae. Sirup sebagai antitusif, contoh
sirup Codeini, mengandung 2 mg Codein/ml sirop.
Sirup sebagai anthelmintik: cotoh sirup Piperazini, mengandung 1 g Piperazine dalam bentuk
hexahydrat/citrat dalam tiap 5 ml sirop. Sirup sebagai antibiotik contohnya yaitu Sirup
Kanamycin, mengandung 50 mg/ml, Sirup Chloramphenicol, umumnya mengandung 25 mg/ml,
Sirup Ampicillin, umumnya mengandung 25 mg/ml, Sirup Amoxycillin, umumnya mengandung
25 mg/ml, Sirup Cloxacillin, umumnya mengandung 25 mg/ml.
Dry Syrup atau sirup kering, berupa campuran obat dengan sakarosa, harus dilarutkan dalam
jumlah air tertentu sebelum dipergunakan. Keuntungan sirup kering dari pada sirup cairan,
biasanya sirup kering dapat tahan disimpan lebih lama. Contohnya Ampicillin trihydrate dry
syrup, ekivalen dengan 25 mg/ml sirup cairan kalau sudah dilarutkan dalam jumlah air yang
ditentukan.
2. Flavored Syrup (sirup korigen/pembawa),

Biasanya tidak digunakan untuk tujuan medis, namun mengandung berbagai bahan aromatis
atau rasa yang enak dan digunakan sebagai larutan pembawa atau pemberi rasa pada berbagai
sediaan farmasi lainnya, misalnya sebagai penutup rasa pahit pada Vitamin B Kompleks yang
diberikan kepada bayi atau anak-anak. Sirup golongan ini, mengandung berbagai bahan
tambahan, misalnya bahan antioksidan (antioxidant agent), pengawet (preservative agent),
pewarna (coloring agent), pemberi rasa (flavoring agent), dan bahan pelarut (diluting agent).
Sirup ini, ditambahkan sebagai korigens rasa untuk obat minum, cukup dalam jumlah 10-20 ml
untuk tiap 100 ml larutan obat.
Sirup yang sering dipakai sebagai korigens-rasa, yaitu Sirup Simpleks, mengandung 65%
gula dalam larutan nipagin 0,25% b/v, Sirup Aurantii, terutama untuk bahan obat yang rasanya
pahit, dan Sirup Rubi Idaei, terutama untuk bahan obat yang rasanya asam.

Komponen Syrup
1. Pemanis
Pemanis berfungsi untuk memperbaiki rasa dari sediaan. Dilihat dari kalori yang dihasilkan
dibagi menjadi pemanis berkalori tinggi dan pemanis berkalori rendah. Adapun pemanis
berkalori tinggi misalnya sorbitol, sakarin dan sukrosa sedangkan yang berkalori rendah seperti
laktosa.
2. Pengawet Antimikroba
Digunakan untuk menjaga kestabilan obat dalam penyimpanan agar dapat bertahan lebih
lama dan tidak ditumbuhi oleh mikroba atau jamur.
3. Perasa dan Pengaroma

Hampir semua sirup disedapkan dengan pemberi rasa buatan atau bahan-bahan yang berasal
dari alam untuk membuat syrup mempunyai rasa yang enak karena sirup adalah sediaan cair,
pemberi rasa ini harus mempunyai kelarutan dalam air yang cukup. Pengaroma ditambahkan ke
dalam syrup untuk memberikan aroma yang enak dan wangi. Pemberian pengaroma ini harus
sesuai dengan rasa sediaan syrup, misalkan syrup dengan rasa jeruk diberi aroma citrus.
4. Pewarna
Pewarna yang digunakan umumnya larut dalam air dan tidak bereaksi dengan komponen
lain dalam syrup dan warnanya stabil dalam kisaran pH selama penyimpanan. Penampilan
keseluruhan dari sediaan cair terutama tergantung pada warna dan kejernihan. Pemilihan warna
biasanya dibuat konsisten dengan rasa. Ada beberapa alasan mengapa sirup itu berwarana, yaitu:
lebih menarik dalam faktor estetikanya serta untuk menutupi kestabilan fisik obat. Juga banyak
sediaan syrup, terutama yang dibuat dalam perdagangan mengandung pelarut-pelarut khusus,
pembantu kelarutan, pengental dan stabilisator.

Keuntungan dan Kerugian Sediaan Syrup


Adapun keuntungan dari sediaan sirup yaitu :
1. Merupakan campuran yang homogen.
2. Dosis dapat diubah-ubah dalam pembuatan.
3. Obat lebih mudah diabsorbsi.
4. Mempunyai rasa manis.
5. Mudah diberi bau-bauan dan warna sehingga menimbulkan daya tarik untuk anak.
6. Membantu pasien yang mendapat kesulitan dalam menelan obat tablet.
Sedangkan kerugian dari sediaan sirup yaitu :

1. Ada obat yang tidak stabil dalam larutan.


2. Volume dan bentuk larutan lebih besar.
3. Ada yang sukar ditutupi rasa dan baunya dalam sirup.

Sifat Fisika Kimia Sirup


1. Viskositas
Viskositas atau kekentalan adalah suatu sifat cairan yang berhubungan erat dengan hambatan
untuk mengalir. Kekentalan didefinisikan sebagai gaya yang diperlukan untuk menggerakkan
secara berkesinambungan suatu permukaan datar melewati permukaan datar lainnya dalam
kondisi mapan tertentu bila ruang diantara permukaan tersebut diisi dengan cairan yang akan
ditentukan kekentalannya. Untuk menentukan kekentalan, suhu zat uji yang diukur harus
dikendalikan dengan tepat, karena perubahan suhu yang kecil dapat menyebabkan perubahan
kekentalan yang berarti untuk pengukuran sediaan farmasi. Suhu dipertahankan dalam batas
tidak lebih dari 0,1 C.
2. Uji mudah tidaknya dituang
Uji mudah tidaknya dituang adalah salah satu parameter kualitas sirup. Uji ini berkaitan erat
dengan viskositas. Viskositas yang rendah menjadikan cairan akan semakin mudah dituang dan
sebaliknya. Sifat fisik ini digunakan untuk melihat stabilitas sediaan cair selama
penyimpanan.Besar kecilnya kadar suspending agent berpengaruh terhadap kemudahan sirup
untuk dituang. Kadar zat penstabil yang terlalu besar dapat menyebabkan sirup kental dan sukar
dituang.
3. Uji Intensitas Warna

Uji intensitas warna dilakukan dengan melakukan pengamatan pada warna sirup mulai
minggu 0-4. Warna yang terjadi selama penyimpanan dibandingkan dengan warna pada minggu
0. Uji ini bertujuan untuk mengetahui perubahan warna sediaan cair yang disimpan Selama
waktu tertentu.

Pembuatan Sirup
Kecuali dinyatakan lain, Sirup dibuat dengan cara sebagai berikut : Buat cairan untuk sirup,
panaskan, tambahkan gula, jika perlu didihkan hingga larut. Tambahkan air mendidih
secukupnya hingga diperoleh bobot yang dikehendaki, buang busa yang terjadi, serkai.
Pada pembuatan sirup dari simplisia yang mengandung glukosida antrakinon, di
tambahkan natrium karbonat sejumlah 10% bobot simplisia. Pada pembuatan sirop simplisia
untuk persediaan di tambahkan Nipagin 0,25% b/v atau pengawet yang cocok.sirop disimpan
dalam wadah tertutup rapar,dan di tempat yang sejuk.
Metode kerja pembuatan sirup yaitu sebagai berikut:
1. Melarutkan bahan- bahan dengan bantuan pemanasan
2.

Sirup yang dibuat dengan cara ini apabila dibutuhkan pembuatan sirup secepat mungkin,
komponen sirup tidak rusak atau menguap oleh pemanasan. Pada cara ini umumnya gula
ditambahkan ke air yang dimurnikan dan dipanaskan sampai larut. Contoh : sirup akasia, sirup
cokelat

3. Melarutkan bahan-bahan dengan pengadukan tanpa pemanasan


Metode ini dilakukan untuk menghindari panas yang merangsang inverse sukrosa. Prosesnya
membutuhkan waktu yang lebih lama tetapi mempunyai kestabilan yang maksimal. Bila bahan
padat akan ditambahkan ke sirup, yang paling baik adalah dengan melarutkannya dalam

sejumlah air murni dan kemudian larutan tersebut digabungkan ke dalam sirup. Contoh : sirup
ferro sulfat.
Penambahan sukrosa pada cairan obat yang dibuat atau pada cairan yang diberi rasa
(Colatura)
Ada kalanya cairan obat seperti tingtur atau ekstrak cair digunakan sebagai sumber obat
dalam pembuatan sirup. Banyak tingtur dan ekstrak seperti itu mengandung bahan-bahan yang
larut dalam alcohol dan dibuat dengan pembawa beralkohol atau hidroalkohol. Jika komponen
yang larut dalam alcohol dibutuhkan sebagai bahan obat dalam pembuatan sirup, beberapa cara
kimia umum dapat dilakukan agar bahan-bahan tersebut larut dalam air, campuran dibiarkan
sampai zat-zat yang tidak larut dalam air terpisah sempurna dan menyaringnya dari campuran.
Filtratnya adalah cairan obat yang kepadanya kemudian ditambahkan sukrosa dalam sediaan
sirup. Pada kondisi lain, apabila tingtur dan ekstrak kental dapat bercampur dengan sediaan
berair, ini dapat ditambahkan langsung ke sirup biasa atau sirup pemberi rasa sebagai obat.
Contoh : Sirup sena.
a.

Maserasi, Perkolasi, dan Infundasi


Adalah cara penarikan sari dari simplisia dengan cara merendam simplisia tersebut dalam
cairan penyari pada suhu biasa yaitu pada suhunya 15-25 0C. Contoh : Sirupus Rhei, Althaeae
sirup
Perkolasi ialah suatu cara penarikan, memakai alat yang disebut perkolator, yang
simplisianya terendam dalam cairan penyari dimana zat-zatnya terlarut dan larutan tersebut akan
menetes secara beraturan keluar sampai memenuhi syarat-syarat yang telah ditetapkan.Contoh
:Sirupus cinnamomi, sirup aurantii corticis. Infundasi adalah ekstraksi ekstraksi cara panas yang
dilakukan dengan menggunakan pelarut air pada temperatur 90 C selama 15 menit.

b. Persyaratan Mutu Dalam Pengerjaan Sirup


Pada pembuatan sirup dari simplisia yang mengandung glikosida antrakinon di tambahkan
Na2CO3 sejumlah 10% bobot simplisia. Kecuali dinyatakan lain, pada pembuatan sirup
simplisia untuk persediaan ditambahkan metil paraben 0,25 % b/v atau pengawet lain yang
cocok. Kadar gula dalam sirup pada suhu kamar maksimum 66 % sakarosa, bila lebih tinggi akan
terjadi pengkristalan, tetapi bila lebih rendah dari 62 % sirup akan membusuk.
Bj sirup kira-kira 1,3. Pada penyimpanan dapat terjadi inversi dari sakarosa ( pecah menjadi
glukosa dan fruktosa ) dan bila sirup yang bereaksi asam inversi dapat terjadi lebih cepat.
Pemanasan sebaiknya dihindari karena pemanasan akan menyebabkan terjadinya gula invert.
Gula invert adalah gula yang terjadi karena penguraian sakarosa yang memutar bidang polarisasi
kekiri. Gula invert tidak dikehendaki dalam sirup karena lebih encer sehingga mudah berjamur
dan berwarna tua (terbentuk karamel), tetapi mencegah terjadinya oksidasi dari bahan obat.
Pada sirup yang mengandung sakarosa 62 % atau lebih, sirup tidak dapat ditumbuhi jamur,
meskipun jamur tidak mati. Bila kadar sakarosa turun karena inversi, maka jamur dapat tumbuh.
Bila dalam resep, sirup diencerkan dengan air dapat pula ditumbuhi jamur. Untuk mencegah
sirup tidak menjadi busuk, dapat ditambahkan bahan pengawet misalnya nipagin. Kadangkadang gula invert dikehendaki adanya misalnya dalam pembuatan sirupus Iodeti ferrosi.Hal ini
disebabkan karena sirup merupakan media yang mereduksi, mencegah bentuk ferro menjadi
bentuk ferri. Gula invert disini dipercepat pembuatannya dengan memanaskan larutan gula
dengan asam sitrat.
Bila cairan hasil sarian mengandung zat yang mudah menguap maka sakarosa dilarutkan
dengan pemanasan lemah dan dalam botol yang tertutup, seperti pada pembuatan Thymi sirupus
dan Thymi compositus sirupus, aurantii corticis sirupus. Untuk cinnamomi sirupus sakarosa

dilarutkan tanpa pemanasan. Maksud menyerkai pada sirup adalah untuk memperoleh sirup yang
jernih. Untuk penjernihan Sirup, dapat dilakukan dengan beberapa cara yaitu : Menambahkan
kocokan zat putih telur segar pada sirup . Didihkan sambil diaduk, zat putih telur akan
menggumpal karena panas. Menambahkan bubur kertas saring lalu didihkan dan saring kotoran
sirup akan melekat ke kertas saring.

Kestabilan Sirup dalam Penyimpan


Cara memasukkan sirup ke dalam botol penting untuk kestabilan sirup dalam penyimpanan,
supaya awet (tidak berjamur ) sebaiknya sirup disimpan dengan cara :
1.

Sirup yang sudah dingin disimpan dalam wadah yang kering. Tetapi pada pendinginan ada
kemungkinan terjadinya cemaran sehingga terjadi juga penjamuran.

2.

Mengisikan sirup panas-panas kedalam botol panas ( karena sterilisasi ) sampai penuh sekali
sehingga ketika disumbat dengan gabus terjadi sterilisasi sebagian gabusnya, lalu sumbat gabus
dicelup dalam lelehan parafin solidum yang menyebabkan sirup terlindung dari pengotoran udara
luar.

3.

Sterilisasi sirup, disini harus diperhitungkan pemanasan 30 menit apakah tidak berakibat
terjadinya gula invert. Maka untuk kestabilan sirup, FI III juga menuliskan tentang panambahan
metil paraben 0,25% atau pengawet lain yang cocok.
Dari ketiga cara memasukkan sirup ke dalam botol ini yang terbaik adalah cara ketiga.
Dalam ilmu farmasi sirup banyak digunakan karena dapat berfungsi sebagai obat, misalnya :
chlorfeniramini maleatis sirupus, Corigensia saporis, misalnya : sirupus simplex, Corigensia
odoris, misalnya : sirupus aurantii, Corigensia coloris, misalnya : sirupus Rhoedos, sirupus rubi

idaei. Pengawet, misalnya sediaan dengan bahan pembawa sirup karena konsentrasi gula yang
tinggi mencegah pertumbuhan bakteri.
Untuk penyimpanan sediaan sirup yaitu dalam wadah tertutup rapat dan di tempat sejuk.
Sedangkan untuk penetapan kadar sakarosa mtode kerjanya yaitu
1. Timbang seksama + 25 gram sirup dalam labu terukur 100 ml, tambahkan 50 ml air dan sedikit
larutan Aluminium hidroksida p. Tambahkan larutan timbal ( II ) sub asetat p tetes demi tetes
hingga tetes terakhir tidak menimbulkan kekeruhan.
2. ]Tambahkan air secukupnya hingga 100,0 ml saring, buang 10 ml filtrat pertama. Masukkan +
45,0 ml filtrat kedalam labu tentukur 50 ml, tambahkan campuran 79 bagian volume asam
klorida p dan 21 bagian vol. Air secukupnya hingga 50,0 ml. Panaskan labu dalam tangas air
pada suhu antara 68 o dan 70 oC selama 10 menit, dinginkan dengan cepat sehingga suhu lebih
kurang 20 oC.
3. Jika perlu hilangkan warna dengan menggunakan tidak lebih dari 100 mg arang penyerap.
4. Ukur rotasi optik larutan yang belum di inversi dan sesudah inversi menggunakan tabung 22,0
cm pada suhu pengukur yang sama antara 10 o dan 25 o C. Hitung kadar dalam %, C12H22O11
dengan rumus :
C = 300 x ( 1 - 2 )
( 144 - 0,5 t )
C = Kadar sacharosa dalam %
1 = rotasi optik larutan yang belum di inversi
2 = rotasi optik larutan yang sudah di inversi
t = suhu pengukuran
Contoh-contoh Sediaan Sirup

1. Ferrosi Iodidi Sirupus


Cara pembuatan : 20 bagian ferrum pulveratum dicampur dengan 60 bagian air, tambahkan
41 bagian Iodium sedikit demi sedikit sambil digerus. Setelah warna coklat hilang maka larutan
disaring, dimasukkan kedalam larutan bagian acidum citricum dan 600 bagian sakarosa dalam
200 bagian air panas. Untuk mencegah terjadinya oksidasi dari ferro Iodida maka ujung corong
masuk kedalam larutan sakarosa. Sisa serbuk besi pada kertas saring dicuci dengan air sampai
diperoleh 1000 bagian sirup.
Guna acidum citricum adalah untuk mempercepat inversi sakarosa, menjadi glukosa dan
fruktosa yang merupakan reduktor kuat yang berguna untuk mencegah oksidasi ferro lodidum.
Ferro Iodidum selalu dibuat baru.
2. Sirupus Simplex = Sirup Gula
Cara pembuatan : larutkan 65 bagian sakarosa dalam larutan metil paraben 0,25 %
secukupnya hingga diperoleh 100 bagian sirup
Pemerian : cairan jernih, tidak berwarna
Penyimpanan : dalam wadah tertutup rapat, di tempat sejuk
3. Auranti Sirupi = Sirup Jeruk Manis
Cara pembuatan : campur 10 bagian kulit buah jeruk manis yang telah dipotong kecil-kecil
dengan 20 bagian larutan metil paraben 0,25%. Biarkan dalam tempat tertutup selama 12 jam.
Pindahkan ke dalam perkolator, perkolasi dengan larutan metil paraben 0,25% secukupnya
hingga diperoleh 37 bagian perkolat. Tambahkan 63 bagian gula pada suhu kamar atau pada
pemanasan perlahan-lahan dalam tempat tertutup hingga diperoleh 100 bagian sirup
Pemerian : cairan kental, jernih, warna coklat, bau khas aromatik.
4. Sirupus Thymi = Sirup Thymi

Cara pembuatan : campurlah 15 bagian herba timi dengan air sesukupnya dan diamkan 12
jam dalam bejana tertutup. Masukan dalam perkolatordan sari dengan air, perkolat dipanasi
sampai 90 0C dan diserkai hingga diperoleh 36 bagian hasil perkolat. Masukan dalam bejana
tertutup dan tambahkan 64 bagian gula panaskan dengan pemanasan lemah hingga diperoleh 100
bagian sirup.
Sirup-sirup yang tercantum dalam FI ed III yaitu :
1. Chlorpheniramini maleatis sirupus
2. Cyproheptadini hydrochloridi sirupus
3. Dextrometorphani hydrobromidi sirupus
4. Piperazini citratis sirupus
5. Prometazini hydrochloridi sirupus
6. Methidilazini hydrochloridi sirupus
7.

Sirupus simplex yang dibuat dengan melarutkan 65 bagian sacharosa dalam larutan metil
paraben secukupnya hingga diperoleh 100 bagian sirup.

8. Dalam perdagangan dikenal dry syrup yaitu syrup berbentuk kering yang kalau akan dipakai
ditambahkan sejumlah pelarut tertentu atau aqua destilata, biasanya berisi zat yang tidak stabil
dalam suasana berair. (Akfar PIM/2010)

Cefadroxil
From Wikipedia, the free encyclopedia
Cefadroxil

Systematic (IUPAC) name


R,7R)-7-{[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino}-3methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2carboxylic acid

Clinical data
Generic

Trade names

AHFS/Drugs.com monograph
a682730

MedlinePlus

Legal status

Routes of
administration

(Prescription
only)

Oral

Pharmacokinetic data
Protein binding
Metabolism

plasma protein
unknown

Biological half-life 1.5 hours


Identifiers
CAS Registry
Number

66592-87-8

ATC code

J01DB05

PubChem

CID: 47964

DrugBank

DB01140

ChemSpider

43629
280111G160

UNII
KEGG

D02353

ChEBI

CHEBI:53667

ChEMBL

CHEMBL1644
Chemical data

Formula
Molecular mass

C16H17N3O5S
363.389 g/mol

SMILES[show]
InChI[show]
(what is this?) (verify)

Cefadroxil (formerly trademarked as Duricef) is a broad-spectrum antibiotic of the


cephalosporin type, effective in Gram-positive and Gram-negative bacterial infections. It is a
bactericidal antibiotic.

Contents

1 General use

2 Spectrum of bacterial resistance and susceptibility

3 Pharmacokinetics

4 Dosage

5 Side effects

6 Dental use

7 Veterinary use

8 References

General use
Cefadroxil is a first-generation cephalosporin antibacterial drug that is the para-hydroxy
derivative of cefalexin, and is used similarly in the treatment of mild to moderate susceptible
infections such as the bacterium Streptococcus pyogenes, causing the disease popularly called
strep throat or streptococcal tonsillitis, urinary tract infection, reproductive tract infection, and
skin infections.

Spectrum of bacterial resistance and susceptibility


Cefadroxil has a broad spectrum of activity and has been effective in treating bacteria
responsible for causing tonsillitis, and infections of the skin and urinary tract. The following
represents MIC susceptibility data for a few medically significant microorganisms.

Escherichia coli: 8 g/ml

Staphylococcus aureus: 1 2 g/ml

Streptococcus pneumoniae: 1 >16 g/ml

[1]

Pharmacokinetics
Cefadroxil is almost completely absorbed from the gastrointestinal tract. After doses of 500 mg
and 1 g by mouth, peak plasma concentrations of about 16 and 30 micrograms/ml, respectively,
are obtained after 1.5 to 2.0 hours. Although peak concentrations are similar to those of
cefalexin, plasma concentrations are more sustained. Dosage with food does not appear to affect
the absorption of cefadroxil. About 20% of cefadroxil is reported to be bound to plasma proteins.
Its plasma half-life is about 1.5 hours and is prolonged in patients with renal impairment.
Cefadroxil is widely distributed to body tissues and fluids. It crosses the placenta and appears in
breast milk. More than 90% of a dose of cefadroxil may be excreted unchanged in the urine
within 24 hours by glomerular filtration and tubular secretion; peak urinary concentrations of
1.8 mg/ml have been reported after a dose of 500 mg. Cefadroxil is removed by haemodialysis.

Dosage
Cefadroxil is given by mouth, and doses are expressed in terms of the anhydrous substance; 1.04
g of cefadroxil monohydrate is equivalent to about 1 g of anhydrous cefadroxil.

Side effects
The most common side effects of cefadroxil are diarrhea (which, less commonly, may be
bloody), nausea, upset stomach, and vomiting. Other side effects include[2] rashes, hives, and
itching.

Dental use
Cefadroxil is used as an antibiotic prophylaxis before dental procedures, for patients allergic to
penicillins.

Veterinary use
It can be used for treating infected wounds on animals. Usually in powder form mixed with
water, it has a color and smell similar to Tang. Given orally to animals, the amount is dependent
on their weight and severity of infection.

Dry syrup Production

Dry syrup
A dry pharmaceutical syrup may be defined as a finely divided insoluble particle
ranging from 0.5-5 , which is to be distributed in a suitable vehicle Dry syrups are
the solid dosage form that can be reconstituted by the addition of water to
administer by the oral route. Mostly antibiotics are available in dry syrup form.
Besides, some moisture sensitive and pediatric drugs are also available in the form
of dry syrup.

Production of Dry Syrup


Mostly antibiotics are available in dry syrup form. Dry syrup at Renata is
manufactured in three methods namely:
Direct Mixing,
Dry Granulation (Slugging) and
Wet Granulation (wet massing).
The flow chart of the above mentioned methods are as follows.
Sealing & Checking
Packaging
Sieving

Blending
Filling
Labeling

Flow Chart of Direct Mixing

Flow chart for Wet granulation

Condition for manufacturing Dry Syrup:


Relative humidity: Not more than 60%.
Temperature: Below 250C
All relevant materials are removed
Equipment is cleaned
Balanced is calibrate
Bottle drying date
When these condition are fulfilled the area is ready for filling of dry syrup and
sighed by :
Production officer
Checked by QA officer

Machines used in Dry Syrup:


1.

Frewitt-Zimmer Mann Chimermann Granulator, Source: Germany.

2.

Karl-Kold Fluid Granulator, Source: Germany.

3.

Ciliotta Bottle Sealing Machine, Source: France.

4.

Macofar Automatic Bottle Filling and Sealing Machine, Source: Italy.

5.

Fitz mill (Sugar Crushing machine), Source: USA.

6.

Multimilling Machine, Source: Bangladesh

7.

Hutt Compactor, Source: Germany

8.

Roller Compactor, Source: India.

9.

Blender Machine (400 kg)

10. Left Gun Bottle Filling Machine, Source: USA.

Monographs: Dosage forms: General monographs: Liquid preparations for oral use

This monograph does not apply to liquids intended for oromucosal administration (for example,
gargles and mouthwashes).
Definition
Liquid preparations for oral use are usually solutions, emulsions or suspensions containing one
or more active ingredients in a suitable vehicle; they may in some cases consist simply of a
liquid active ingredient used as such. Liquid preparations for oral use are either supplied in the
finished form or, with the exception of Oral emulsions, may also be prepared just before issue for
use by dissolving or dispersing granules or powder in the vehicle stated on the label.
The vehicle for any liquid preparation for oral use is chosen having regard to the nature of the
active ingredient(s) and to provide organoleptic characteristics appropriate to the intended use of
the preparation. Liquid preparations for oral use may contain suitable antimicrobial
preservatives, antioxidants and other excipients such as dispersing, suspending, thickening,
emulsifying, buffering, wetting, solubilizing, stabilizing, flavouring and sweetening agents and
authorized colouring matter.
Liquid preparations for oral use may be supplied as multidose or as single-dose preparations.
Each dose from a multidose container is administered by means of a device suitable for
measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL or
multiples thereof, or an oral syringe for other volumes or, for Oral drops, a suitable dropper.
Additional information. Liquid preparations for oral use are often the dosage form of choice for
paediatric use.
Owing to the wide range of liquid preparations for oral use and their long history of use, a
variety of terms has been used to describe different members of this category of preparation.
These terms, which are not mutually exclusive and the definitions of which have changed over
time, include elixirs, linctuses, milks, mixtures and syrups. Such terms are still used within the
titles of certain specific, long-established, traditional preparations (for example, ephedrine elixir,
codeine linctus, acid gentian mixture). With such exceptions, however, it is recommended that
the titles of liquid dosage forms for oral use are based on the terms used as sub-monograph
headings in this general monograph. The term syrup (denoting a solution containing a high
proportion of sucrose) is used, inter alia, for certain solutions (for example, black currant syrup,
lemon syrup) that are used as vehicle ingredients for their sweetening and flavouring properties.
Such syrups are not dosage forms in the pharmacopoeial sense: they do not contain any active
ingredient and are not intended to be administered as such.
Oral solutions containing one or more active ingredients dissolved in a vehicle containing a high
proportion of sucrose or a suitable polyhydric alcohol or alcohols and which may contain ethanol

have traditionally been called elixirs. Viscous oral solutions containing one or more active
ingredients dissolved in a vehicle containing a high proportion of sucrose, other sugars or a
suitable polyhydric alcohol or alcohols and which are intended for use in the treatment or relief
of cough have traditionally been called linctuses. They are intended to be sipped and swallowed
slowly without the addition of water.
Manufacture
The manufacturing process for liquid preparations for oral use should meet the requirements of
Good Manufacturing Practice (GMP).
The following information is intended to provide broad guidelines concerning the critical steps to
be followed during production of liquid preparations for oral use.
In the manufacture of liquid preparations for oral use, measures are taken to:
ensure that all ingredients are of appropriate quality
minimize the risk of microbial contamination (see recommendations in chapter
MICROBIOLOGICAL QUALITY OF NON-STERILE PRODUCTS: RECOMMENDED
ACCEPTANCE CRITERIA FOR PHARMACEUTICAL PREPARATIONS of the
supplementary information section.);
minimize the risk of cross-contamination
During the development of a preparation, the formulation for which contains one or more
antimicrobial preservatives, the effectiveness of the chosen preservative system shall be
demonstrated to the satisfaction of the relevant regulatory authority.
Appropriate measures should also be taken to optimize the stability of the active ingredient(s) in
liquid formulations including those prepared from powder or granules. Additional measures
should be taken so that, when stored under the conditions stated on the label, oral solutions are
not subject to precipitation and oral suspensions are not subject to fast sedimentation, lump
formation or caking.
During development of a single-dose liquid preparation for oral use it shall be demonstrated that
the nominal content can be withdrawn from the container.
In the production of liquid preparations for oral use containing dispersed particles, measures are
taken to ensure a suitable and controlled particle size and, where appropriate, crystal structure
(polymorphic and/or solvated forms) with regard to the intended use.
Throughout manufacturing, certain procedures should be validated and monitored by carrying
out appropriate in-process controls. These should be designed to guarantee the effectiveness of
each stage of production. In-process controls during the manufacture of oral liquids should

include pH and fill volume. The validation of the manufacturing process and the in-process
controls are documented.
Safety concerns
An important aspect of Good Manufacturing Practice for all pharmaceutical products is assuring
the quality of all the starting materials used. The need for analytical testing to check the identity
and quality of starting materials is explained in detail in section 14 of the current WHO GMP
guidelines1. Failure to ensure that starting materials are of the required quality can have very
serious consequences.
Increasingly countries are dependent on the importation of starting materials for use in the
production of medicines. Starting materials often change hands many times before reaching the
manufacturer of the final marketed product and there are many opportunities for the material to
undergo relabelling along the distribution and trade chain (see WHO Guideline on Good Trade
and Distribution Practices for Pharmaceutical Starting Materials1). As a result, starting materials
required for production of pharmaceutical products can become contaminated or materials may
be supplied that no longer correspond to what is stated on the label in terms of quality or
identity, either accidentally or as a result of negligence and sometimes fraud.
The most documented incidents of contamination involve liquid preparations for oral use
manufactured with excipients such as glycerol and propylene glycol that have been
contaminated, adulterated or mixed up with diethylene glycol. Such incidents have been
responsible for hundreds of deaths throughout the world (see, for example, editorial in WHO
Bulletin 2001, 79(2)). Ingestion of diethylene glycol often leads to death through kidney failure.
1

For the current edition of WHO guidelines, please consult the WHO Medicines web site:
http://www.who.int/medicines/en/.
Uniformity of mass
Liquid preparations for oral use that are presented as single-dose preparations comply with the
following test. Weigh individually the contents of 20 containers, emptied as completely as
possible, and determine the average mass. Not more than 2 of the individual masses deviate by
more than 10% from the average mass and none deviates by more than 20%.
Uniformity of mass of doses delivered by the measuring device
The measuring device provided with a multidose liquid preparation for oral use complies with
the following test. Weigh individually 20 doses taken at random from one or more multidose
containers with the measuring device provided and determine the individual and average masses.
Not more than two of the individual masses deviate by more than 10% from the average mass
and none deviates by more than 20%.

Containers
The containers should be made of material that will not adversely affect the quality of the
preparation by, for example, leaching or sorption. Liquid preparations for oral use that contain
light-sensitive active ingredients are supplied in containers that are light-resistant.
Except where indicated in the individual monograph, containers should be made from material
that is sufficiently transparent to permit the visual inspection of the contents.
If the preparation contains volatile ingredients, the liquid preparation for oral use should be kept
in a tightly closed container.
Labelling
Every pharmaceutical preparation must comply with the labelling requirements established under
Good Manufacturing Practice.
The label should include:
(1) the name of the pharmaceutical product;
(2) the name(s) of the active ingredients; INNs should be used wherever possible;
(3) the amount of active ingredient in a suitable dose-volume;
(4) the name and concentration of any antimicrobial preservative and the name of any other
excipient;
(5) the batch (lot) number assigned by the manufacturer;
(6) the expiry date and, when required, the date of manufacture;
(7) any special storage conditions or handling precautions that may be necessary;
(8) directions for use, warnings, and precautions that may be necessary;
(9) the name and address of the manufacturer or the person responsible for placing the product
on the market.
If the Liquid preparation for oral use is supplied as granules or powder to be constituted just
before issue for use, the label should include:
(1) that the contents of the container are granules or powder for the preparation of an oral liquid;
(2) the strength as the amount of the active ingredient in a suitable dose-volume of the
constituted preparation;
(3) the directions for preparing the oral liquid including the nature and quantity of liquid to be
used;
(4) the storage conditions and shelf-life of the constituted preparation.
Requirements for specific types of liquid preparations for oral use
Oral solutions

Definition
Oral solutions are clear Liquid preparations for oral use containing one or more active
ingredients dissolved in a suitable vehicle.
Visual inspection
Inspect the solution. It should be clear and free from any precipitate. A change in colour or
cloudiness of solutions may indicate chemical degradation or microbial contamination.
Oral suspensions
Definition
Oral suspensions are Liquid preparations for oral use containing one or more active ingredients
suspended in a suitable vehicle. For oral suspensions containing more than one active ingredient,
some of the active ingredients may be in solution.
Oral suspensions may show a sediment which is readily dispersed on shaking to give a uniform
suspension which remains sufficiently stable to enable the correct dose to be delivered.
Visual inspection
Inspect the suspension. Evidence of physical instability is demonstrated by the formation of
flocculants or sediments that do not readily disperse on gentle shaking. A change in colour may
indicate chemical degradation or microbial contamination.
Uniformity of content. For oral suspensions that are presented as single-dose preparations and
that contain less than 5 mg of active ingredient per dose or in which the active ingredient is less
than 5% of the total weight per dose, carry out the following test. Shake and empty each
container as completely as possible and carry out the test as described under 5.1 Uniformity of
content for single-dose preparations. In such cases, the test for Uniformity of mass prescribed
above is not required.
Labelling
The label on the container should include a direction that the bottle should be shaken before use.
Oral emulsions
Definition
Oral emulsions are Liquid preparations for oral use containing one or more active ingredients.
They are stabilized oil-in-water dispersions, either or both phases of which may contain
dissolved solids. Solids may also be suspended in Oral emulsions.
Oral emulsions may show evidence of phase separation but are readily redispersed on shaking.

Visual inspection
Inspect the emulsion. Evidence of physical instability is demonstrated by phase separation that is
not readily reversed on gentle shaking. A change in colour of emulsions may indicate chemical
degradation or microbial contamination.
Containers
When issued for use, Oral emulsions should be supplied in wide-mouthed bottles.
Labelling
The label on the container should include a direction that the bottle should be shaken before use.
Oral drops
Definition
Oral drops are Liquid preparations for oral use that are intended to be administered in small
volumes with the aid of a suitable measuring device. They may be solutions, suspensions or
emulsions.
Visual inspection
Inspect the drops. Drops that are solutions should be clear and free from any precipitate.
Evidence of physical instability of drops that are suspensions is demonstrated by the formation of
flocculants or sediments that do not readily disperse on gentle shaking. Evidence of physical
instability of drops that are emulsions is demonstrated by phase separation that is not readily
reversed on gentle shaking. A change in colour (or cloudiness of solutions) may indicate
chemical degradation or microbial contamination of the drops.
Dose and uniformity of dose of oral drops
Into a suitable, graduated cylinder, introduce by means of the dropping device the number of
drops usually prescribed for one dose or introduce by means of the measuring device the usually
prescribed quantity. The dropping speed does not exceed 2 drops per second. Weigh the liquid,
repeat the addition, weigh again and carry on repeating the addition and weighing until a total of
10 masses are obtained. No single mass deviates by more than 10% from the average mass. The
total of 10 masses does not differ by more than 15% from the nominal mass of 10 doses. If
appropriate, measure the total volume of 10 doses. The volume does not differ by more than 15%
from the nominal volume of 10 doses.
Containers
Oral drops are normally supplied in suitable multidose containers that allow successive drops of
the preparation to be administered.
Powders for oral solutions, oral suspensions or oral drops

Presentations of powder (usually single-dose presentations, for example, a small sachet) that are
intended to be issued to the patient as a powder, to be taken in or with water or another suitable
liquid, are outside the scope of this general monograph. Such preparations are controlled by the
monograph for Oral powders.
Definition
Powders for oral solutions, suspensions or drops are multidose preparations consisting of solid,
loose, dry particles of varying degrees of fineness. They contain one or more active ingredients,
with or without excipients and, if necessary, authorized colouring matter and flavouring
substances. They may contain antimicrobial preservatives and other excipients in particular to
facilitate dispersion or dissolution and to prevent caking.
After dissolution or suspension in the prescribed liquid, they comply with the requirements for
Oral solutions, Oral suspensions or Oral drops, as appropriate.
Manufacture
In the manufacture of powders for oral solutions, suspensions or drops, the components of the
powder mixture are passed through a sieve to remove lumps and particle aggregates. The
weighed masses of the sieved components, preferably of a narrow particle size distribution, are
then transferred to a suitable mixer. The greatest risk of segregation of the powder mixture
usually occurs when emptying the mixer container and when the powder mixture is dosed into
the containers. Ensuring the suitability of the mixing equipment and the dosing devices is,
therefore, critical.
Visual inspection
Inspect the powder. Evidence of physical instability is demonstrated by noticeable changes in
physical appearance, including texture (for example, clumping). A change in colour may indicate
chemical degradation or microbial contamination.
Granules for oral solutions or suspensions
Presentations of granules that are intended to be issued to the patient as granules to be
swallowed as such, to be chewed, or to be taken in or with water or another suitable liquid, are
outside the scope of this general monograph.
Definition
Granules for oral solutions or suspensions are multidose preparations consisting of solid, dry
aggregates of powder particles sufficiently resistant to withstand handling. They contain one or
more active ingredients with or without excipients and, if necessary, authorized colouring matter
and flavouring substances. They may contain antimicrobial preservatives and other excipients in
particular to facilitate dispersion or dissolution and to prevent caking.

After dissolution or suspension in the prescribed liquid, they comply with the requirements for
Oral solutions or Oral suspensions, as appropriate.
Visual inspection
Inspect the granules. Evidence of physical instability is demonstrated by noticeable changes in
physical appearance, including texture (for example, clumping of granules, presence of loose
powder). A change in colour may indicate chemical degradation or microbial contamination.

Monographs: Dosage forms: General monographs: Oral powders

The requirements of this monograph do not necessarily apply to powders to be used for the
preparation of oral solutions or suspensions.
Definition
Oral powders are preparations consisting of solid, loose, dry particles of varying degrees of
fineness. They contain one or more active ingredients, with or without excipients and, if
necessary, authorized colouring matter and flavouring substances. They are generally
administered in or with water or another suitable liquid. They may also be swallowed directly.
They are presented as single-dose or multidose preparations.
Each dose of a single-dose powder is enclosed in an individual container, for example a packet, a
sachet or a vial. Multidose oral powders require the provision of a measuring device capable of
delivering the quantity prescribed.
Manufacture
The manufacturing process for oral powders should meet the requirements of Good
Manufacturing Practice (GMP).
The following information is intended to provide broad guidelines concerning the critical steps to
be followed during production of oral powders.
In the manufacture of oral powders, measures are taken to:
ensure that there is a suitable particle size range with regard to the intended use;
minimize the risk of microbial contamination;
minimize the risk of cross-contamination.
Appropriate measures should also be taken to counteract segregation of the components of the
powder mixture. Segregation takes place whenever a free-flowing powder consisting of particles
of a range of sizes is handled, including the mixing stage and emptying of the mixer container.
The prime means to counteract segregation is to use components of similar particle size. In cases
where the risk of segregation is significant, oral powders containing a low proportion of the
active ingredient, for example, less than 5% of total mass, should preferably be prepared as
single-dose preparations.
In the production of oral powders, the components of the powder mixture are passed through a
sieve to remove lumps and particle aggregates. The weighed masses of the sieved components,
preferably of a narrow particle size distribution, are then transferred to a suitable mixer. The
greatest risk of segregation of the powder mixture usually occurs when emptying the mixer

container and when the powder mixture is dosed into the containers. Ensuring the suitability of
the mixing equipment and the dosing devices is therefore critical.
Throughout manufacturing certain procedures should be validated and monitored by carrying out
appropriate in-process controls. These should be designed to guarantee the effectiveness of each
stage of production. In-process controls during the manufacture of oral powders should include
the dosing by mass of the powder into the containers.
The validation of the manufacturing process and the in-process controls are documented.
The intended mass of one dose of an oral powder should be at least 500 mg to minimize the
effect of loss of powder when taken from a single-dose container or to allow a proper dosing
when using a measuring device.
Visual inspection
Inspect the powder, using at least 20 containers for single-dose preparations. Evidence of
physical and/ or chemical instability is demonstrated by noticeable changes in physical
appearance, including texture [e.g. clumping] or colour.
Uniformity of content
See the general requirements 5.1 Uniformity of content for single-dose preparations. Single-dose
oral powders with a content of active ingredient of less than 5 mg or less than 5% of the total
mass comply with the test, unless otherwise specified in the individual monograph. If the
preparation has more than one active ingredient, the requirement applies only to those active
ingredients that fall into the above category.
Uniformity of mass
See the general requirements 5.2 Uniformity of mass for single-dose preparations. Single-dose
oral powders comply with the test. If the test for uniformity of content is prescribed for all active
ingredients, the test for uniformity of mass is not required.
Uniformity of mass of doses delivered by the measuring device
The measuring device provided with a multidose oral powder complies with the test. Weigh
individually 20 doses taken at random from one or more multidose containers with the measuring
device provided and determine the individual and average masses. Not more than two of the
individual masses deviate by more than 10% from the average mass and none deviates by more
than 20%.
Labelling
Every pharmaceutical preparation must comply with the labelling requirements established under
GMP.

The label should include:


(1) the name of the pharmaceutical product;
(2) the name(s) of the active ingredients; INNs should be used wherever possible;
(3) for single-dose preparations, the amount of the active ingredient(s) per container and for
multidose preparations, the amount of active ingredient in a suitable quantity by weight;
(4) the batch (lot) number assigned by the manufacturer;
(5) the expiry date and, when required, the date of manufacture;
(6) any special storage conditions or handling precautions that may be necessary;
(7) directions for use, warnings, and precautions that may be necessary;
(8) the name and address of the manufacturer or the person responsible for placing the product
on the market.
Storage
If the preparation contains volatile or hygroscopic ingredients, the oral powder should be kept in
tightly closed container.
Requirements for specific types of oral powder
Effervescent powders
Definition
Effervescent powders are presented as single-dose or multidose preparations and generally
contain acidic substances and carbonates or hydrogen carbonates which react rapidly in the
presence of water to release carbon dioxide. They are intended to be dissolved or dispersed in
water before administration.
Storage
Effervescent powders should be kept in tightly closed containers.

Methods of Analysis: 5. Pharmaceutical technical procedures: 5.5 Dissolution test for


solid oral dosage forms
2014-01

This text is based on the internationally-harmonized texts developed by the Pharmacopoeial


Discussion Group (PDG). It has been developed in line with the style and requirements used in
The International Pharmacopoeia. The additional section on monographs of The International
Pharmacopoeia is not part of the PDG text.
For further guidance, see also the chapter Dissolution testing of tablets and capsules in the
Supplementary Information section.
This test determines the amount of active ingredient(s) released from a solid oral dosage form,
such as a tablet or a capsule, under controlled conditions using a known volume of dissolution
medium within a predetermined length of time.
Basket apparatus. The assembly consists of the following: a vessel, which may be covered,
made of glass or other inert, transparent material, which should not sorb, react or interfere with
the dosage form, the active ingredient or the dissolution medium; a motor; a drive shaft; and a
cylindrical basket. The vessel is partially immersed in a suitable water-bath of any convenient
size or heated by a suitable device such as a heating jacket to maintain the temperature inside the
vessel at 37 0.5 C during the test and to keep the dissolution medium in constant, smooth
motion. No part of the assembly, including the environment in which the assembly is placed,
contributes significant motion, agitation or vibration beyond that due to the smoothly rotating
stirring element. Apparatus that permits observation of the preparation and stirring element
during the test is preferable. The vessel is cylindrical, with a hemispherical bottom and a capacity
of 1 litre. Its height is 160210 mm and its inside diameter is 98 106 mm. Its sides are flanged
at the top. A fitted cover may be used to retard evaporation. If a cover is used it provides
sufficient openings to allow ready insertion of the thermometer and withdrawal of samples. The
shaft is positioned so that its axis is not more than 2 mm at any point from the vertical axis of the
vessel and rotates smoothly and without significant wobble that could affect the results. A speedregulating device is used that allows the shaft rotation speed to be selected and maintained at a
specified rate within 4%.
Shaft and basket components of the stirring element are fabricated of stainless steel, type 316 or
equivalent, to the specifications shown in Figure 1. A basket having a gold coating of about 2.5
m (0.0001 inch) thick may be used. The dosage unit is placed in a dry basket at the beginning
of each test. The distance between the inside bottom of the vessel and the bottom of the basket is
maintained at 25 2 mm during the test.

1) Screen with welded seam: 0.220.31 mm wire diameter with wire opening of 0.360.44 mm.
After welding the screen may be slightly altered.
2) Maximum allowable runout at A is 1.0 mm when the part is rotated on centre line axis with
basket mounted.
Figure 1. Basket stirring element

Dimensions in millimetres

A and B dimensions do not vary more than 0.5 mm when part is rotated on centre line axis.
Tolerances are 1.0 mm unless otherwise stated.
Figure 2. Paddle stirring element.

Dimensions in millimetres
Paddle Apparatus. Use the assembly from Basket apparatus except that a paddle formed from a
blade and a shaft is used as the stirring element. The shaft is positioned so that its axis is not
more than 2 mm from the vertical axis of the vessel at any point and rotates smoothly without
significant wobble that could affect the results. The vertical centre line of the blade passes
through the axis of the shaft so that the bottom of the blade is flush with the bottom of the shaft.
The paddle conforms to the specifications shown in Figure 2. The distance of 25 2 mm
between the bottom of the blade and the inside bottom of the vessel is maintained during the test.
The metallic or suitably inert, rigid blade and shaft comprise a single entity. A suitable two-part
detachable design may be used provided the assembly remains firmly engaged during the test.
The paddle blade and shaft may be coated with a suitable coating so as to make them inert. The
dosage unit is allowed to sink to the bottom of the vessel before rotation of the blade is started. A
small, loose piece of nonreactive material, such as not more than a few turns of wire helix, may
be attached to dosage units that would otherwise float. An alternative sinker device is shown in
Figure 3. Other validated sinker devices may be used.

Figure 3. Alternative sinker. Dimensions in millimeters.


Recommended procedure
Conventional-release (or immediate-release) dosage forms
Procedure. Place the stated volume of the dissolution medium ( 1%) in the vessel of the
specified apparatus. Assemble the apparatus, equilibrate the dissolution medium to 37 0.5 C,
and remove the thermometer. The test may also be carried out with the thermometer in place,
provided it is shown that results equivalent to those obtained without the thermometer are
obtained. Place one dosage unit in the apparatus, taking care to exclude air bubbles from the

surface of the dosage unit. Operate the apparatus at the specified rate. Within the time interval
specified, or at each of the times stated, withdraw a sample from a zone midway between the
surface of the dissolution medium and the top of the rotating basket or blade, not less than 1 cm
from the vessel wall. Where multiple sampling times are specified replace the samples
withdrawn for analysis with equal volumes of fresh dissolution medium at 37 C or, where it can
be shown that replacement of the medium is not necessary, correct for the volume change in the
calculation. Keep the vessel covered for the duration of the test and verify the temperature (37
0.5 C) of the medium at suitable times. Perform the analysis as directed in the individual
monograph using a suitable assay method. Test samples are filtered immediately upon sampling
using in-line filtration, unless filtration is demonstrated to be unnecessary. Use an inert filter that
does not cause adsorption of the active substance or contain extractable substances that would
interfere with the analysis. Centrifugation is not recommended unless validated for the specific
test. The test is to be conducted with six dosage form units in parallel.
If automated equipment is used for sampling or the apparatus is otherwise modified, verification
is necessary that the modified apparatus will produce results equivalent to those obtained with
the apparatus described in this chapter.
Dissolution medium. A suitable dissolution medium is used. The volume specified refers to
measurements made between 20 C and 25 C. If the dissolution medium is a buffered solution
adjust the solution so that its pH is within 0.05 units of the specified pH. Dissolved gases can
cause bubbles to form, which may change the results of the test. In such cases, dissolved gases
must be removed prior to testing.1
1

One appropriate method of deaeration is as follows: heat the medium, while stirring gently, to
about 41 C, immediately filter under vacuum using a filter having a pore size of 0.45 m or less,
with vigorous stirring and continue stirring under vacuum for at least 5 min, preferably 15 min,
until no more bubbles are observed. Other validated deaeration techniques for removal of
dissolved gases may be used.
Time. Where a single time specification is given the test may be concluded in a shorter period if
the requirement for minimum amount dissolved is met. Samples are to be withdrawn only at the
stated times, within a tolerance of 2%.
Determine the quantity of active ingredient dissolved at the specified time(s) indicated in the
individual monograph. The result should be expressed as a percentage of the content stated on
the label of the dosage form.
Sustained-release solid dosage forms
Procedure. Proceed as described for conventional-release dosage forms.

Dissolution medium. Proceed as described for conventional-release dosage forms.


Time. The test-time points, generally 3, are expressed in hours.
Delayed-release, solid dosage forms
Procedure. Use method A or B
Method A
Acid stage. Place 750 mL hydrochloric acid (0.1 mol/l) VS in the vessel and assemble the
apparatus. Allow the medium to equilibrate to a temperature of 37 0.5 C. Place one dosage
unit in the apparatus, cover the vessel and operate the apparatus at the specified rate. After 2 h of
operation in hydrochloric acid (0.1 mol/l) VS withdraw a sample of the fluid and proceed
immediately as directed under Buffer stage. Perform an analysis of the sample using a suitable
assay method.
Buffer stage. Complete the operations of adding and adjusting the pH within 5 min. With the
apparatus operating at the rate specified add to the fluid in the vessel 250 mL of a 0.2 M solution
of trisodium orthophosphate R that has been equilibrated to 37 0.5 C. Adjust, if necessary,
with hydrochloric acid (~70 g) TS or sodium hydroxide (~80 g/l) TS to a pH of 6.8 0.05.
Continue to operate the apparatus for 45 min or for the specified time. At the end of the time
period withdraw a sample of the fluid and perform the analysis using a suitable assay method.
Method B
Acid Stage. Place 1000 mL of hydrochloric acid (0.1 mol/l) VS in the vessel and assemble the
apparatus. Allow the medium to equilibrate to a temperature of 37 0.5 C. Place one dosage
unit in the apparatus, cover the vessel and operate the apparatus at the specified rate. After 2
hours of operation in hydrochloric acid (0.1 mol/l) VS withdraw a sample of the fluid and
proceed immediately as directed under Buffer stage. Perform an analysis of the sample using a
suitable assay method.
Buffer stage. For this stage of the procedure use buffer that has previously been equilibrated to
a temperature of 37 0.5 C. Drain the acid from the vessel and add 1000 mL of pH 6.8
phosphate buffer, prepared by mixing three volumes of hydrochloric acid (0.1 mol/l) VS with one
volume of a 0.20 M solution of trisodium orthophosphate R and adjusting, if necessary, with
hydrochloric acid (~70 g/l) TS or sodium hydroxide (~80 g/l) TS to a pH of 6.8 0.05. This may
also be accomplished by removing from the apparatus the vessel containing the acid and
replacing it with another vessel containing the buffer and transferring the dosage unit to the
vessel containing the buffer. Continue to operate the apparatus for 45 minutes or for the specified

time. At the end of the time period withdraw a sample of the fluid and perform the analysis using
a suitable assay method.
Time. All test times stated are to be observed within a tolerance of 2%, unless otherwise
specified.
Acceptance criteria
Conventional-release (or immediate-release) dosage forms
Unless otherwise specified in the individual monograph the requirements are met if the quantities
of active ingredient(s) dissolved from the dosage forms tested conform to Table 1. Continue
testing through the three levels unless the results conform at either S1 or S2. The quantity, Q, is
the specified amount of dissolved active ingredient expressed as a percentage of the labelled
content; the 5%, 15% and 25% values in the acceptance table are percentages of the labelled
content so that these values and Q are in the same terms.
Table 1
Level Samples tested

Acceptance criteria

S1

Each value is not less than Q + 5%

S2

Average value of the 12 dosage units (S1 + S2) is equal to or


greater than Q and no unit is less than Q-15%

S3

12

Average value of 24 dosage units (S1 + S2 + S3) is equal to or


greater than Q; not more than 2 units are less than Q - 15%;
no unit is less than Q - 25%.

Sustained release dosage forms


Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of active ingredient(s) dissolved from the dosage forms tested conform to Table 2.
Continue testing through the three levels unless the results conform at either L1 or L2. Limits on
the amounts of active ingredient(s) dissolved are expressed in terms of the labelled content. The
limits embrace each value of Qi , the amount dissolved at each specified fractional dosing
interval. Where more than one range is specified the acceptance criteria apply individually to
each range.
Table 2

Level Samples tested

Acceptance criteria

L1

No individual value lies outside each of the stated ranges and


no individual value is less than the stated amount at the final
test time

L2

The average value of the 12 dosage units (L1 + L2) lies within
each of the stated ranges and is not less than the stated
amount at the final test time; none is more than 10% of the
labelled content outside each of the stated ranges; and none is
more than 10% of labelled content below the stated amount
at the final test time

L3

12

The average value of the 24 dosage units (L1 + L2 + L3) lies


within the stated ranges and is not less than the stated amount
at the final test time; not more than 2 of the 24 dosage units
are more than 10% of labelled content outside each of the
stated ranges; not more than 2 of the 24 dosage units are
more than 10% of labelled content below the stated amount
at the final test time; and none of the 24 dosage units is more
than 20% of labelled content below the stated content at the
final test time; none of the units are more than 20% of
labelled content outside each of the stated ranges or more
than 20% of labelled content below the stated amount at the
final test time

Delayed-release dosage forms


Acid stage. Unless otherwise stated in the individual monograph the requirements of this part of
the test are met if the quantities, based on the percentage of the labelled content of active
ingredient(s) dissolved from the dosage units tested conform to Table 3. Continue testing through
the three levels unless the results of both acid and buffer stages conform at an earlier level.
Table 3
Level Samples tested

Acceptance criteria

A1

No individual value exceeds 10% dissolved

A2

Average value of the 12 dosage units (A1 + A2) is not more


than 10% dissolved, and no individual value is greater than

25% dissolved
A3

12

Average value of 24 dosage units (A1 + A2 + A3) is not more


than 10% dissolved, and no individual value is greater than
25% dissolved.

Buffer stage. Unless otherwise specified in the individual monograph the requirements are met if
the quantities of active ingredients dissolved from the units tested conform to Table 4. Continue
testing through the three levels unless the results of both stages conform at an earlier level. The
value of Q in Table 4 is the specified total amount of API dissolved in both the acid and buffer
stages, expressed as a percentage of the labelled content. The 5%, 15% and 255 values in the
table are percentages of the labelled content so that these values and Q are in the same terms.
Table 4
Level Samples tested

Acceptance criteria

B1

No value is less than Q + 5%

B2

Average value of the 12 dosage units (B1 + B2) is equal to or


greater than Q, and no unit is less than Q - 15%

B3

12

Average value of the 24 dosage units (B1 + B2 + B3) is equal


to or greater than Q; not more than 2 units are less than Q 15%, and no unit is less than Q - 25%.

Monographs of The International Pharmacopoeia


The following additional statements apply to the individual monographs of The International
Pharmacopoeia.
Performance of dissolution test equipment
Periodically verify the performance of the equipment2 utilizing an appropriate mechanical
procedure or reference tablet.
2

For example, use the mechanical process described in International Standard procedure ASTM
2503-07 or reference tablets such as those available from the United States Pharmacopeia
Convention Inc., every 6 12 months for each individual system.
Test conditions

The following specifications are given in the individual monographs:


the apparatus to be used;
the composition and volume of the dissolution medium;
the rotation speed of the paddle or basket;
the preparation of the test and reference solutions;
the time, the method and the amount for sampling of the test solution or the conditions
for continuous monitoring;
the method of analysis;
the limits of the quantity or quantities of active pharmaceutical ingredient(s) required to
dissolve within a prescribed time.
Dissolution media
If a buffer is added to the dissolution medium adjust its pH to within 0.05 units of the
prescribed value.
In specific cases, and subject to approval by the relevant regional or national authority,
dissolution media may contain enzymes and/or surfactants. The addition of enzymes may be
considered, for example, for formulations containing gelatin in the outer layer when dissolution
failures can be ascribed to the cross-linking of this excipient (e.g. hard and soft gelatin
capsules).For the testing of preparations containing poorly aqueous-soluble active substances
modification of the medium may be necessary. In such circumstances a low concentration of
surfactant may be prescribed.
Below are some examples of dissolution media:
Dissolution buffer pH 1.3, TS
Dissolve 2 g of sodium chloride R in 800 mL of water R, adjust the pH to 1.3 with hydrochloric
acid (~70 g/l) TS and dilute to 1000 mL with water R.
Dissolution buffer pH 2.5, TS

Dissolve 2 g of sodium chloride R in 800 mL of water R, adjust the pH to 2.5 with hydrochloric
acid (~70 g/l) TS and dilute to 1000 mL with water R.
Dissolution buffer pH 3.5, TS
Dissolve 7.507 g of glycine R and 5.844 g of sodium chloride R in 800 mL of water R, adjust the
pH to 3.5 with hydrochloric acid (~70 g/l) TS and dilute to 1000 mL with water R.
Dissolution buffer pH 4.5, TS
Dissolve 6.8 g of potassium dihydrogen phosphate R in 900 mL of water R, adjust the pH to 4.5
either with hydrochloric acid (~70 g/l) TS or sodium hydroxide (~80 g/l) TS and dilute to 1000
mL with water R.
Dissolution buffer, pH 6.8, TS
Dissolve 6.9 g of sodium dihydrogen phosphate R and 0.9 g of sodium hydroxide R in 800 mL of
water R, adjust the pH to 6.8 with sodium hydroxide (~80g/l) TS and dilute to 1000 mL with
water R.
Dissolution buffer, pH 6.8, 0.25% SDS TS
Dissolve 6.9 g of sodium dihydrogen phosphate R, 0.9 g of sodium hydroxide R and 2.5 g of
sodium dodecyl sulfate R in 800 mL of water R, adjust the pH to 6.8 with sodium hydroxide
(~80g/l) TS and dilute to1000 mL with water R.
Dissolution buffer pH 7.2, TS
Dissolve 9.075 g of potassium dihydrogen phosphate R in water R to produce 1000 mL (solution
A). Dissolve 11.87 g of disodium hydrogen phosphate R in sufficient water R to produce 1000
mL (solution B). Mix 300 mL of solution A with 700 mL of solution B.
Gastric fluid, simulated, TS
Dissolve 2.0 g of sodium chloride R and 3.2 g of pepsin R in 7.0 mL of hydrochloric acid (~420
g/l) TS and sufficient water R to produce 1000 mL. This test solution has a pH of about 1.2.
Intestinal fluid pH 6.8, simulated, TS
Mix 77.0 mL of sodium hydroxide (0.2 mol/l) VS , 250.0 mL of a solution containing 6.8 g
potassium dihydrogen phosphate R and 500 mL of water R. Add 10.0 g pancreatin R, mix and
adjust pH to 6.8 0.1. Dilute to 1000 mL with water R.

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