Injection dosage form: without and with stabilizers Author: as. Yu.Yu. Plaskonis

Injection dosage forms - a specific group of drugs that require special conditions of preparation, the strictest adherence to aseptic, technological discipline, full responsibility for the preparation, quality control and design to dispensing drugs.

Injection solutions are prepared in aseptic unit

Aseptic conditions - defined conditions, and complex institutional arrangements required to enable to save the drugs from getting into these microorganisms.

Technology process of preparation solutions for injection consists of the following stages:  Preparation of aseptic unit and the organization of work in aseptic conditions.  Preparation of vessels and auxiliary materials.  Preparation of solvents and drugs.  dissolved drugs.  stabilization or isotones solutions (if need)  Quality control solutions.  Filtering solutions to filling bottles, checking the absence of mechanical inclusions.  closing, leak check, preparation for sterilization (marking).  Sterilization.  Quality control and design of drugs to dispense.

Preparatory work

Solutions prepare by volumetric- mass method in which medical substances take by weight, and solvent added to obtain the desired volume of solution.

Dissolution

Stability is achieved by adding stabilizers or use of special methods of preparation. Stabilization solutions when necessary

Analysis

Filtering solutions

Corking bottles

Sterilization- solutions exposed within 1,5-2 hours after manufacture. The only exception is glucose, which sterilized immediately after production. Sterilization by autoclaving:  volume less than 100 ml- 8 min  volume from 100 to 500 ml- 12 min  volume more than 500 ml- 15 min

Stability of drug injection is achieved compliance with the aseptic conditions of their preparation, choice of optimal conditions (temperature, time) sterilization, antimicrobial use valid tools to achieve the effect of sterilization at lower temperatures and also the use of stabilizers - substances that enhance the chemical stability injecting drugs in the solutions.

Stabilizers can be divided into three groups:  substances which provide chemical stabilization - antioxidants that prevent oxidation.  substances which prevent the hydrolysis of salts  Antiseptics providing microbiological stabilization.

№Name of matter which needs to stabilization Stabilizator 1Solutions of salts, formed by weak bases and strong acids (atropine sulfate, Scopolamine hydrobromide, cocaine hydrochloride, pilocarpine hydrochloride, Novocain, Strychnine nitrate, Dibazol et al) Acid hydrochloride (HCl) -10 ml a 0,1 M solution on 1 liter Novocain of 0,25% - 3 ml a 0,1 M on 1 liter Novocain of 0,5%- 4 ml a 0,1 M on 1 liter Novocain of 1% - 9 ml a 0,1 M on 1 liter Novocain of 2% - 12 ml a 0,1 M on 1 liter 2Solutions of salts, formed by strong bases and weak acids (sodium nitrite, caffeine- benzoate of sodium, sodium thiosulphate, euphillin) Sodium hydroxide (NaOH) 0.1 M 10%, 20% caffeine- benzoate of sodium- 4 ml 0.1 M on 1 liter 30% caffeine- benzoate of sodium- 20 ml 0.1 M on 1 liter 3Solutions of easily oxidable substances (acid ascorbic, vicasol, sodium salicylate, streptocide, adrenalin hydrotartrat) Streptocide 5%, 10% - sodium sulfit 2 g on 1 liter of solution Sodium salicylate 10% -sodium metabisulfite- a 1 g on 1 liter of solution Acid ascorbic 5% - sodium metabisulfite- 2 g on 1 liter of solution 4Solution of glucose A stabilizator of Weibel (is composition: sodium chloride- 5,2 g, acids chloride - 4,4 ml water for the injections to 1 liter. Stabilizator is added by 5% from the volume of solution, which needs to be stabilized.

The main changes in drugs are chemical processes: oxidation hydrolysis isomerization

Pharmaceutics used antioxidants that slow oxidation and prevent the formation of active radicals. The most effective of them are phenols, naftolum, aminofenolum, aromatic amines.

Effective antioxidants are substances that deplete hydro peroxide (sodium sulfit, sodium meta-bisulfit, tiosechovyna, ronhalit, unitiol) But there are other antioxidants, such as paraaminofenol, ascorbic acid.

Rp.: Solutionis Acidi ascorbinici 5% 50 ml Sterilisa! Da. Signa

TECHNOLOGY stabilize ascorbic acid solutions introduction antioxidant sodium metabisulfitis 1 g for liter or solution sodium sulphite anhydrous 2 g for1 liter. stabilize ascorbic acid solutions introduction antioxidant sodium metabisulfitis 1 g for liter or solution sodium sulphite anhydrous 2 g for1 liter. In addition, solutions of ascorbic acid strongly acidic. In order to neutralize the environment of the sodium carbonate solution is introduced g per 1 liter. In aseptic conditions in sterile volumetric flask dissolve 2.5 g of ascorbic acid, 1.19 sodium hydrogen carbonate and 0.1 g anhydrous sodium sulphite in part freshly prepared water for injection. After the allocation of gas bubbles make up the solution to 50 ml, mixed, filtered in sterile bottles and sterilized at 120 ° C 8 min. Issuing labels "for injection", "aseptically”. In aseptic conditions in sterile volumetric flask dissolve 2.5 g of ascorbic acid, 1.19 sodium hydrogen carbonate and 0.1 g anhydrous sodium sulphite in part freshly prepared water for injection. After the allocation of gas bubbles make up the solution to 50 ml, mixed, filtered in sterile bottles and sterilized at 120 ° C 8 min. Issuing labels "for injection", "aseptically”.

WPC (front side) Date № рецепта Natrii sulfitis anhydrici 0,1 Acidi ascorbinici 2,5 Natrii hydrocarbonatis 1,19 Aquae pro injectionibus ad 50 ml V = 50 ml Sterilis Prepared:Signature Checked:Signature

Hydrolysis - a reaction of ion exchange between drugs and water. Hydrolysis are different classes of compounds: alkaloids, glycoside, vitamins, esters, proteins, carbohydrates and especially salt. Hydrolysis are only salt in which one or both components are weak.

Hydrolysis of salts formed by weak base and strong acid, and their stabilization. This group includes salts of alkaloids containing synthetic nitrogen bases (solutions of salts of novocaine, dybazol, strychnine nitrate, etc.).. This group of salts stabilize adding 0.1 M solution of hydrochloric acid, since excess hydroxyl ions (OH +3) reduces the degree of dissociation of water and suppresses hydrolysis, causing a shift of equilibrium to the left.

Rp.: Solutionis Novocaini 0,5% 100 ml Sterilisa! Da. Signa

For stabilization the 0.5% solution of novocaine 0.1 M hydrochloric acid solution to pH 3,8-4,5 taking 4 ml for 1 liter solution. Sterilizing at 120  С 8 min. Issuing blue label "for injection", which indicate: solution of novocaine 0.5% 100 ml for infiltration anesthesia, aseptically.

WPC (front side) Date№ recipe Aquae pro injectionibus 100 ml Novocaini 0,5 Solutionis Аcidi hydrocarbonici 0,1 M gtts. VIII V = 100 мл Sterilis Prepared:Signature Checked:Signature

Stabilization of glucose For stabilization glucose added stabilizer by Veybel’, prepare for the prescription: Natrii chloridi 5.2 ml Hydrochloric acid 4.4 ml Water for injection to 1 liter When preparing glucose, regardless of its concentration, stabilizer added 5% by volume solution. When preparing glucose, regardless of its concentration, stabilizer added 5% by volume solution.

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