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Croscarmellose Sodium

1 Nonproprietary Names
BP: Croscarmellose sodium
PhEur: Carmellosum natricum conexum
USPNF: Croscarmellose sodium

2 Synonyms
Ac-Di-Sol; crosslinked carboxymethylcellulose sodium; Explocel; modified cellulose gum; Nymcel ZSX; Pharmacel
XL; Primellose; Solutab; Vivasol.

3 Chemical Name and CAS Registry Number Cellulose,


carboxymethyl ether, sodium salt, crosslinked [74811-65-7]

4 Empirical Formula and Molecular Weight


Croscarmellose sodium is a crosslinked polymer of carboxymethylcellulose sodium.
See Carboxymethylcellulose sodium.

5 Structural Formula
See Carboxymethylcellulose sodium.

6 Functional Category
Tablet and capsule disintegrant.

7 Applications in Pharmaceutical Formulation


or Technology
Croscarmellose sodium is used in oral pharmaceutical formulations as a disintegrant for capsules,(1,2) tablets,(3–13)
and granules. In tablet formulations, croscarmellose sodium may be used in both direct-compression and wet-
granulation processes. When used in wet granulations, the croscarmellose sodium should be added in both the
wet and dry stages of the process (intra- and extragranularly) so that the wicking and swelling ability of the
disintegrant is best utilized.(11,12) Croscarmellose sodium at concentrations up to 5% w/w may be used as a tablet
disintegrant, although normally 2% w/w is used in tablets prepared by direct compression and 3% w/w in tablets
prepared by a wet-granulation process.

8 Description
Croscarmellose sodium occurs as an odorless, white or grayishwhite powder.
9 Pharmacopeial Specifications
See Table II.
Table II: Pharmacopeial specifications for croscarmellose sodium.

10 Typical Properties
Acidity/alkalinity: pH = 5.0–7.0 in aqueous dispersions.
Bonding index: 0.0456
Brittle fracture index: 0.1000
Density (bulk): 0.529 g/cm3 for Ac-Di-Sol(7)
Density (tapped): 0.819 g/cm3 for Ac-Di-Sol(7)
Density (true): 1.543 g/cm3 for Ac-Di-Sol(7)
Particle size distribution:
Ac-Di-Sol: not more than 2% retained on a #200 (73.7 mm)
mesh and not more than 10% retained on a #325 (44.5 mm) mesh.
Pharmacel XL: more than 90% less than 45 mm, and more
than 98% less than 100 mm in size.
Solubility: insoluble in water, although croscarmellose sodium rapidly swells to 4–8 times its original volume on
contact with water. Practically insoluble in acetone, ethanol and toluene. Specific surface area: 0.81–0.83m2/g

11 Stability and Storage Conditions


Croscarmellose sodium is a stable though hygroscopic material.
A model tablet formulation prepared by direct compression,
with croscarmellose sodium as a disintegrant, showed no
significant difference in drug dissolution after storage at 308C
for 14 months.(9)
Croscarmellose sodium should be stored in a well-closed
container in a cool, dry place.
12 Incompatibilities
The efficacy of disintegrants, such as croscarmellose sodium, may be slightly reduced in tablet formulations
prepared by either the wet-granulation or direct-compression process that contain hygroscopic excipients such as
sorbitol.(10) Croscarmellose sodium is not compatible with strong acids or with soluble salts of iron and some other
metals such as aluminum, mercury, and zinc.
13 Method of Manufacture
Alkali cellulose is prepared by steeping cellulose, obtained from wood pulp or cotton fibers, in sodium hydroxide
solution. The alkali cellulose is then reacted with sodium monochloroacetate to obtain carboxymethylcellulose
sodium. After the substitution reaction is completed and all of the sodium hydroxide has been used, the excess
sodium monochloroacetate slowly hydrolyzes to glycolic acid. The glycolic acid changes a few of the sodium
carboxymethyl groups to the free acid and catalyzes the formation of crosslinks to produce croscarmellose
sodium. The croscarmellose sodium is then extracted with aqueous alcohol and any remaining sodium chloride or
sodium glycolate is removed. After purification, croscarmellose sodium of purity greater than 99.5% is obtained.(4)
The croscarmellose sodium may be milled to break the polymer fibers into shorter lengths and hence improve its
flow properties.

14 Safety
Croscarmellose sodium is mainly used as a disintegrant in oral pharmaceutical formulations and is generally
regarded as an essentially nontoxic and nonirritant material. However, oral consumption of large amounts of
croscarmellose sodium may have a laxative effect, although the quantities used in solid dosage formulations are
unlikely to cause such problems. In the UK, croscarmellose sodium is accepted for use in dietary supplements. The
WHO has not specified an acceptable daily intake for the related substance carboxymethylcellulose sodium, used
as a food additive, since the levels necessary to achieve a desired effect were not considered sufficient to be a
hazard to health.(14) See also Carboxymethylcellulose sodium.

15 Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of material handled. Croscarmellose
sodium may be irritant to the eyes; eye protection is recommended.

16 Regulatory Status
Included in the FDA Inactive Ingredients Guide (oral capsules, granules, sublingual tablets, and tablets). Included in
nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal
Ingredients.

17 Related Substances
Carboxymethylcellulose calcium; carboxymethylcellulose sodium.

18 Comments
Typically, the degree of substitution (DS) for croscarmellose sodium is 0.7.
Hand book of pharmaceutical
1 Nama Nonproprietary

BP: Croscarmellose sodium

PhEur: Carmellosum natricum conexum

USPNF: Croscarmellose sodium

2 Sinonim

Ac-Di-Sol; natrium karboksimetilselulosa silang; Explocel; ganggang selulosa termodifikasi; Nymcel ZSX; Pharmacel
XL; Primellose; Solutab; Vivasol.

3 Nama Kimia dan Nomor Pendaftaran CAS Selulosa,

karboksimetil eter, garam natrium, ikatan silang [74811-65-7]

4 Rumus Empiris dan Berat Molekul

Natrium kroskarmelosa adalah polimer silang dari natrium karboksimetilselulosa.

Lihat Carboxymethylcellulose sodium.

5 Formula Struktural

Lihat Carboxymethylcellulose sodium.

6 Kategori Fungsional

Tablet dan disintegran kapsul.

7 Aplikasi dalam Formulasi Farmasi atau Teknologi

Natrium kroskarmelosa digunakan dalam formulasi farmasi oral sebagai disintegran untuk kapsul, (1,2) tablet, (3-
13) dan granul. Dalam formulasi tablet, natrium kroskarmelosa dapat digunakan baik dalam proses kompresi

langsung dan granulasi basah. Ketika digunakan dalam granulasi basah, natrium kroskarmelosa harus
ditambahkan baik pada tahap basah dan kering dari proses (intra dan ekstragranular) sehingga kemampuan
wicking dan pembengkakan disintegran paling baik digunakan. (11,12) Croscarmellose sodium di konsentrasi
hingga 5% b / b dapat digunakan sebagai disintegran tablet, meskipun biasanya 2% b / b digunakan dalam tablet
yang dibuat dengan kompresi langsung dan 3% b / b dalam tablet yang disiapkan dengan proses granulasi basah.

8 Keterangan

Natrium kroskarmelosa muncul sebagai bubuk putih yang tidak berbau, putih atau keabu-abuan.

10 Properti Khas

Keasaman / alkalinitas: pH = 5,0-7,0 dalam dispersi berair.

Indeks pengikat: 0,0456

Indeks fraktur rapuh: 0,1000

Densitas (curah): 0,529 g / cm3 untuk Ac-Di-Sol (7)

Kepadatan (disadap): 0,819 g / cm3 untuk Ac-Di-Sol (7)

Kepadatan (true): 1,543 g / cm3 untuk Ac-Di-Sol (7)

Distribusi ukuran partikel:

Ac-Di-Sol: tidak lebih dari 2% disimpan pada # 200 (73,7 mm)

mesh dan tidak lebih dari 10% disimpan pada mesh # 325 (44,5 mm).

Pharmacel XL: lebih dari 90% kurang dari 45 mm, dan banyak lagi

dari 98% kurang dari 100 mm.

Kelarutan: tidak larut dalam air, meskipun natrium kroskarmelosa cepat membengkak menjadi 4-8 kali volume
aslinya saat bersentuhan dengan air. Praktis tidak larut dalam aseton, etanol dan toluena. Luas permukaan spesifik:
0,81-0,83m2 / g

11 Kondisi Stabilitas dan Penyimpanan

Natrium kroskarmelosa adalah bahan higroskopis yang stabil.

Formulasi tablet model yang disiapkan dengan kompresi langsung,

dengan natrium kroskarmelosa sebagai disintegran, tidak menunjukkan


perbedaan yang signifikan dalam pembubaran obat setelah penyimpanan pada 308C

selama 14 bulan. (9) Natrium kroskarmelosa harus disimpan dalam keadaan tertutup wadah di tempat yang sejuk
dan kering.

12 Inkompatibilitas

Kemanjuran disintegrants, seperti natrium kroskarmelosa, dapat sedikit direduksi dalam formulasi tablet yang
dibuat dengan proses granulasi basah atau proses kompresi langsung yang mengandung eksipien higroskopis
seperti sorbitol. (10) Natrium kroskarmelosa tidak kompatibel dengan asam kuat atau dengan garam larut besi dan
beberapa logam lain seperti aluminium, merkuri, dan seng.

13 Metode Pembuatan

Selulosa alkali dibuat dengan mendidih selulosa, diperoleh dari pulp kayu atau serat kapas, dalam larutan natrium
hidroksida. Selulosa alkali kemudian direaksikan dengan natrium monokloroasetat untuk memperoleh natrium

karboksimetilselulosa. Setelah reaksi substitusi selesai dan semua natrium hidroksida telah digunakan, natrium
monokloroasetat yang berlebih secara perlahan menghidrolisis menjadi asam glikolat. Asam glikolat mengubah
beberapa gugus natrium karboksimetil menjadi asam bebas dan mengkatalisis pembentukan ikatan silang untuk
menghasilkan natrium kroskarmelosa. Natrium kroskarmelosa kemudian diekstraksi dengan alkohol berair dan
natrium klorida atau natrium glikolat yang tersisa dihilangkan. Setelah pemurnian, natrium silang-silang kemurnian
lebih besar dari 99,5% diperoleh. (4) Natrium kroskarmelosa dapat digiling untuk memecahkan serat polimer

menjadi panjang yang lebih pendek dan karenanya meningkatkan sifat alirannya.

14 Keselamatan

Natrium kroskarmelosa terutama digunakan sebagai disintegrant dalam formulasi farmasi oral dan umumnya
dianggap sebagai bahan yang pada dasarnya tidak beracun dan tidak berbahaya. Namun, konsumsi oral sejumlah
besar natrium kroskarmelosa mungkin memiliki efek pencahar, meskipun jumlah yang digunakan dalam formulasi

dosis padat tidak mungkin menyebabkan masalah seperti itu. Di Inggris, natrium kroskarmelosa diterima untuk
digunakan dalam suplemen diet. WHO belum menetapkan asupan harian yang dapat diterima untuk substansi
yang terkait karboksimetilselulosa natrium, digunakan sebagai aditif makanan, karena tingkat yang diperlukan
untuk mencapai efek yang diinginkan tidak dianggap cukup untuk menjadi bahaya bagi kesehatan. (14) Lihat juga
Carboxymethylcellulose sodium.

15 Tindakan Pencegahan Penanganan


Amati kewaspadaan normal sesuai dengan keadaan dan kuantitas material yang ditangani. Natrium kroskarmelosa
dapat mengiritasi mata; pelindung mata dianjurkan.

16 Status Regulasi

Termasuk dalam FDA Inactive Ingredients Guide (kapsul oral, granula, tablet sublingual, dan tablet). Termasuk
dalam obat-obatan nonparenteral yang berlisensi di Inggris. Termasuk dalam Daftar Kanada Bahan Non-obat
yang Dapat Diterima.

17 Zat Terkait

Karboksimetilselulosa kalsium; carboxymethylcellulose sodium.

18 Komentar

Biasanya, tingkat substitusi (DS) untuk natrium kroskarmelosa adalah 0,7.


martindale 36

Croscarmellose Sodium (USAN)


Carmellosum natricum conexum; Croscarmellose sodique; Croscarmelosa sódica;
Crosslinked Carboxymethylcellulose Sodium; E468; Kroskarmelioze˙s natrio druska;
Kroskarmelloosi natrium; Kroskarmellosnatrium; Kroskarmelosa sodná sůl; Kroskarmeloza
sodowa; Kroszkarmellóz-nátrium; Modified Cellulose Gum.

Pharmacopoeias. In Eur. (see p.vii) and Jpn. Also in USNF.


Ph. Eur. 6.2 (Croscarmellose Sodium). A cross-linked polymer of carmellose sodium. A white or
greyish-white powder. Practically insoluble in dehydrated alcohol, in acetone, and in toluene. A 1%
suspension in water has a pH of 5.0 to 7.0.

USNF 26 (Croscarmellose Sodium). The sodium salt of a crosslinked partly O-


(carboxymethylated) cellulose. A white, freeflowing powder. Partially soluble in water; insoluble in
alcohol, in ether, and in other organic solvents. pH of a dispersion containing 1 g mixed with 100 mL
of water for 5 minutes is between 5.0 and 7.0.

Uses and Administration


Carmellose calcium and carmellose sodium have a variety of pharmaceutical uses, including use as
suspending, thickening, and emulsifying agents, and as disintegrants, binders, and coating agents in
tablets. Carmellose sodium is also used as an emulsifier or stabiliser in the food industry.
Croscarmellose sodium is used as a tablet disintegrant. Carmellose sodium is used topically as an
ingredient of protective preparations for stoma care, in the management of wounds, and for the
mechanical protection of oral and perioral lesions, such as mouth ulceration (p.1700). It is also used,
in concentrations of up to 1%, in artificial saliva preparations for the treatment of dry mouth (p.2140),
and in eye drops for the management of dry eye (p.2140). Carmellose sodium given orally absorbs
water and acts as a bulkforming agent; the volume of faeces is increased and peristalsis promoted. It is
used in the treatment of constipation (p.1693). Carmellose sodium has been included in preparations
to control appetite in the management of obesity (p.2149) but there is little evidence of efficacy. For
precautions to be observed with bulkforming agents, see under Methylcellulose, p.2145.

Preparations
BP 2008: Carmellose Sodium Eye Drops;
USP 31: Carboxymethylcellulose Sodium Paste; Carboxymethylcellulose Sodium Tablets.
Proprietary Preparations (details are given in Part 3)
Arg.: Aqua Lent Lagrima†; Aqua Lent Lubricante; Aquacel; Aucic; Cellufresh†; Celluvisc†;
Comfeel; Comfeel Plus Transparente; Natura Fresh; Nu- Derm Hidrocoloide; Refresh
Liquigel; Refresh Tears; Austral.: Aquacel†; Cellufresh; Celluvisc; Refresh Liquigel; Refresh
Tears Plus†; Austria: Celluvisc;
Belg.: Gelilact; Braz.: Cellufresh; Ecofilm; Fresh Tears; Lacrifilm; Salivan;
Canad.: Aquacel†; Refresh Celluvisc; Refresh Liquigel; Refresh Plus; Refresh
Tears; Chile: Refresh Liquigel; Refresh Tears; Cz.: Cellufluid; Denm.: Celluvisc;
Fin.: Celluvisc; Fr.: Aquacel; Askina Biofilm†; Biatain; Celluvisc; Clip
Ampoules; Clip Brulures; Comfeel; Hydrocoll; Physiotulle; Sureskin; Urgomed;
Urgotul; Ger.: Algoplaque; Alione; Cellufresh; Cellumed; Celluvisc;
Comfeel Plus Transparenter; Physiotulle; Urgotul; Gr.: Cellufluid; Celluvisc;
Hong Kong: Refresh; Irl.: Celluvisc; Israel: Refresh Tears; Ital.: Cellufresh;
Celluvisc; Lacrilens; Malaysia: Refresh Plus†; Refresh Tears†; Mex.: Celluvisc†;
Novafix Ultra Fuerte; Refresh Liquigel; Refresh Tears; Thera Tears†;
Neth.: Celluvisc; NZ: Cellufresh†; Celluvisc†; Refresh Tears Plus; Philipp.:
Cellufresh; Celluvisc; Port.: Aquacel†; Askina Biofilm†; Cellufluid; Celluvisc;
S.Afr.: Cellufresh; Celluvisc; Comfeel; Refresh Liquigel; Refresh Tears; Singapore:
Celluvisc; Refresh Plus†; Refresh Tears†; Spain: Cellufresh; Celluvisc;
Viscofresh; Swed.: Celluvisc; Switz.: Cellufluid; Celluvisc; Thai.: Cellufresh;
Celluvisc; UK: Celluvisc; Comfeel; Intrasite; Physiotulle; USA:
Celluvisc; Clear Eyes for Dry Eyes; Optive; Refresh Plus; Refresh Tears; Tears
Again; TheraTears; Venez.: Refresh Liquigel; Refresh Tears.
Multi-ingredient: Arg.: Comfeel Plus; Comfeel Purilon†; Comfeel Sea-
Sorb†; Humectante Bucal; Mucobase; Purilon; Razagleda Plus†; Seasorb;
Austral.: Aquae; Orabase; Orahesive†; SoloSite; Stomahesive†; Austria:
Glandosane; Sialin; Braz.: Chofranina; Canad.: Appedrine†; Carboflex†;
Orabase†; Orahesive†; Salivart; Tegasorb; Chile: Delgadol Fibra; K.C.M.C;
Novafix Extra Fuerte; Reducform-F; Salivart†; Cz.: Alginete†; Spofax; Fr.:
Altreet Ag; Amivia†; Aquacel Ag; Artisial; Askina Sorb†; Biatain Argent; Cellosorb;
Clip Hemo; Intrasite; Melgisorb; Purilon; Release Ag; Seasorb; Urgosorb;
Urgotul S.Ag; Ger.: Cellosorb; Comfeel Plus; Glandosane; Lary-
Phary; Nu-Gel†; Purilon; Recatol Algin; SeaSorb Soft; Hong Kong: Aquae;
Glandosane; Salivart; India: Digene; Irl.: Orabase; Israel: Orabase†; Ital.:
Aquacel Ag; NZ: Orabase; Stomahesive; Port.: Askina Sorb†; Carboflex†;
Glandosane; Varihesive†; S.Afr.: Granuflex; Granugel; Orabase; Spain:
Laxvital; Switz.: Glandosane; Thai.: Bisolax; Emulax; Glandosane†; UK:
Comfeel Plus; Glandosane; Luborant; Orabase; Orahesive; Physiotulle-Ag;
SeaSorb Soft; Seprafilm; Stomahesive; USA: Entertainer’s Secret; Moi-Stir;
Pretts Diet Aid; Salivart; Seprafilm; Surgel; Venez.: Klincosal; Novafix; Polantac.