parenteral preparation

zulfiayu,S1UNG,may 2012

parenteral
Parenteral (Gk, para enteron= beside the intestine) Parenteral administration of drugs involves the injection of therapeutic agents, in the form of solutions, suspensions or emulsions, into the body. In so doing, one of the major barriers to drug entry (the skin) is breeched.

5 general categories of injection

1. Solution ready for injection 2. Dry, soluble products ready to be combined with a solvent just prior to use 3. Suspensions ready for injection 4. Dry, insoluble products ready to be combined with a vehicle just prior to use 5. Emulsions

Route of administration
Intravenous Subcutaneous Intradermal Intramuscular Intraarticular Intrathecal

Macam cara penyuntikan

Injeksi intravena (i.v)
Injeksi iv yg diberikan dlm dosis tunggal dgn volume >10 ml disebut infus intravena/infus/infundabilia. Infus harus bebas pirogen, tdk boleh mengandung bakterisida, jernih, dan isotonis. Injeksi i.v dgn volume 15 ml atau lbh tdk boleh mengandung bakterisida. Inj.i.v dgn volume 10 ml atau lebih harus bebas pirogen.

Macam cara penyuntikan

Inj. Intraarterium (i.a)
Disuntikkan ke dlm pembuluh darah arteri/perifer/tepi, volume 1-10 ml, tdk boleh mgndung bakterisida

Injeksi intrakordal/intrakardiak (i.kd)

Disuntikkan langsung ke dlm otot jantung atau ventrikel, tdk boleh mgandung bakterisida, disuntikkan hanya dlm keadaan gawat

Macam cara penyuntikan

Inj.intratekal (i.t), intraspinal, intrasisternal (i.s),intadural (i.d), subaraknoid
Disuntikkan lgsung ke dlm saluran sumsum tulang belakang di dasar otak (antara 3-4 atau 5-6 lumbar vertebrata) tempat terdapatnya cairan cerebrospinal. Larutan harus isotonis krn sirkulasi ciaran serebrospinal lambat, meskipun lar.anestetik u sumsum tulang sering hipertonis. Jar saraf di daerah anatomi ini sangat peka

Macam cara penyuntikan

Intraartikular
Disuntikkan ke dalam cairan sendi di dalam rongga sendi. Benutknya suspensi atau alrutan dlm air.

Injeksi subkonjungtiva
Disuntikkan ke dalam selaput lendir di bawah mata. Berupa suspensi atu larutan, tidak lebih dari 1 ml

Macam cara penyuntikan

Inj.intrabursa
Disuntikkan ke dlm bursa subcromillis atau bursa olecranon dlm bentuk lar.suspensi dlm air

Inj.intraperitoneal (i.p)
Disuntiikan langsung ke dalam rongga perut. Penyerapan berlangusng cepat, namun bahaya infeksi besar

Macam cara penyuntikan

Inj.peridural (p.d), ekstradural, epidural
Disuntikkan kedalam ruang epidural, terletak di atas durameter, lapisan penutup terluar dari otak dan sumsum tulang belakang

Advantages
Immedidiate physiological action is nedded Patient cant not be given orally because of the unconscious or uncooperative state of the patient, or because of inactivation or lack of absorption in the intestinal tract.

Disadvantages
The requirement of aseptis at administation The risk of tissue factor and difficulty in correcting an error If a direct pharmacological antagonist is immediately available, correction of an error may be impossible Daily or frequent administration poses difficulties, either for the patient to visit a professionally trained person or to learn to inject oneself

pH optimal
pH optimal u darah atau cairan tubuh yg lain ad 7,4 dan disebut isohidri. Krn tdak semua bahan obat stabil pd pH cairan tubuh, injeksi sering dibuat di luar pH cairan tubuh dan berdasar kestabilan bahan tsb.

Pengaturan pH lar injeksi diperlukan u :

1. Menjamin stabilitas obat, mis perubahan warna, efek terapi optimal obat,menghindari kemungkinan terjadinya reaksi dr obat tsb. 2. Mencegah terjadinya rangsangan atau rasa sakit sewaktu disuntikkan. pH>>> : nekrosis jaringan pH<<< : rasa sakit jika disuntikkan

Isotonis
1. Punya tek.osmosis yg sama dgn tekanan osmosis cairan tubuh (darah, cairan lumbar, air mata) bernilai sama dgn tekanan osmosis lar.NaCl 0,9% b/v 2. Mempunyai titik beku yg sama dgn titik beku cairan tubuh, yi -0,52C <<< NaCl 0,9% b/v : hipotonis >>> NaCl 0,9% b/v : hipertonis

 Hipotonis disuntikkan : air dr lar.inj akan diserap dan masuk ke dalam sel, akibatnya sel akan mengembang dan pecah (haemoolisis), bersifat tetap. Pecah sel ini akan dibawa aliran darah dan dpt menyumbat pembuluh darah yg kecil Hipertonis disuntikkan : air dlm sel akan ditarik keluar dr sel shg sel akan mengerut, bersifat sementara dan tdk menimbulkan kerusakan sel.

 Hipotonis disuntikkan : air dr lar.inj akan diserap dan masuk ke dalam sel, akibatnya sel akan mengembang dan pecah (haemoolisis), bersifat tetap. Pecah sel ini akan dibawa aliran darah dan dpt menyumbat pembuluh darah yg kecil Hipertonis disuntikkan : air dlm sel akan ditarik keluar dr sel shg sel akan mengerut, bersifat sementara dan tdk menimbulkan kerusakan sel.

Cara mendapatkan isoioni

Isoioni : lar.inj tsb mengandung ion-ion yg sama dgn ion-ion yg terdapat dlm darah, yaitu K+, Na+, Mg2+, Ca2+, Cl-. Isoioni diperlukan pd penyuntikan dlm jumlah besar, mis: pd infus intravena

sterilization
The complete destruction or removal of all forms of live from materials The process by which living organisms are removed or killed to this extent that they are no longer detectable in standard culture media in which they have previously have been found to proliferate

definition
Antiseptic : a substance which, when aplied to microorganism, renders them innocuous either by killing them or preventing their growth Asepsis : the prevention of access of viable microorganism to materials or process Bactericide: a substance or process thatt kills bacteria

 Disinfectant : agent that frees from infection/chemical substance that destroy pathogenic bacteria Germicide : a chemical substance which kills mo but not necessary bacterial spores Preservative : a chemical agent that prevents microbial decomposition or growth in the product

 Sanitizer : an agent or process that produce the number of bacterial contaminants to safe level as jugged by public health requirements Sporacide : a process or substance that destroys microbial spores, especially bacterial spores Virucide : any process or substance that destroys or inactivates viruses

Kind of sterilization
1. 2. 3. 4. 5. 6. 7. Sterilization by moist heat Sterilization by dry heat Sterilization by ionizing radiation Gaseous sterilization with ethylene oxide Sterilization with liquid chemical sterilization by uv radiation Sterilization by filtation

Skema pembuatan secara aseptik

Bahan Obat Zat pembawa (steril) Zat pembantu (steril)

Alat utk pembautan (gelas)

Dicuci Wadah (ampul, vial) Dicuci disterilkan diisi ditutup kedap dikarantina Sibwei etiket dan dikemas diperiksa disterilkan dilarutkan (ruang steril

Skema pembuatan secara non-aseptik

Bahan Obat Zat pembawa Zat pembantu

Alat utk pembautan (gelas)

Dicuci Wadah (ampul, vial) Dicuci dilarutkan (ruang steril) disaring diisi dan ditutup kedap disterilkan dikarantina Sibwei etiket dan dikemas diperiksa

components
Vehicles Solutes Containers Closures

production
Maintaining facilities and equipment Preparing and controlling the environment Cleaning the containers and equipment Preparing the product Filtering the solution Filling containers with the product Sealing the containers

Control of quality
Evaluation of components Validation of equipment and processes Determination with the prescribed requirements Performance of necessary evaluative test on the finished product

Packaging and labelling

All steps necessary to identify the finished product and enclose it in manner that is safely and properly prepared for sale and delivery to the user

Component and containers

Essential first step establishing spesifications to insure the quality of each of the components of an injection

vehicle
Since most liquid injections are quite dilute, the component present in the highest proportion No therapeutic activity and nontoxic The vehicle of greatest importance water Prepared by distillation or by reserve osmosis.

Types of vehicles
Aqueous vehicles isotonicc to which a drug may be added at the time of administration Water miscible vehicles Non aqueous vehicles effect solubility and to reduce hydrolysis Nonaqueous vehicles

solutes
Requirements for purity Level of microbial and pyrogenic contamination Solubility characteristic as determined by the chemical or physical form of the compound Freedom from the dirt

Added substances
Effect solubility Provide patient comfort Enhance the chemical stability of the solution Preserve a preparation against the growth of microorganism

Antimicrobial agents
USP states that antimicrobial agents in bacteriostatic or fungistatic concentrations must be added to preparations contained in multiple-dose containers Adequate concentration at the of use to prevent the multiplication of the microorganisms inadvertently introduced into the preparation while withdrawing a portion of the contents with a hypodemic needle and syringe

Antimicrobial agents
Phenylmercuric nitrate and thimerosal 0,01% (most frequently 0,002%) Metil apraben and propyl paraben (0,18%/0,02% in combination) Benzethonium chloride and benzalkonium chloride 0,01% Phenol or cresol 0,05% Chlorobutanol 0,5%

buffers
Used primarily to stabilize a solution againts the chemical degradation that might be occur if the pH changes appreciably. Buffer systems employed should normally have as low a buffer cappacity as feasible in order not to disturb significantly the body buffer system when injected Ex: acid salts (citrates, acetates, phosphates)

antioxidants
To preserve products because of the ease with the which many drugs are oxidizes Ex: sodium bisulfite 0,1%

PYROGENS
Anticipated contaminants in crude drugs, such as antibiotics produced by fermentation, or they may be present as unexpected and unwanted contaminants in a finished product as result of inadvertent contamination during processing.

process
The former must be: eliminated during the purification steps of the drugs Eliminated best by prebventing their introduction or development during the process

 Pyrogens cause a febrile reaction in human beings. Symptoms : chills, pains in the back and legs and malaise, if fatal : significant discomfort for the patients Recent findings indicate that bacterial pyrogens, when introduced into the body, stimulate the production of an endogenus (leukocytic) pyrogen that causes the familiar physological responses

 Pyrogens are products of the growth of microorganism. The most potent pyrogenic substances are produced by gram negative bacteri (endotoxins), but gram positive bacteria and fungi also produce pyrogenic substances of lesser potential

containers
Plastic Glass

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