Injection dosage form: Injection dosage form: without and with without and with stabilizersstabilizers

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 Technology process of preparation solutions for injection consists of the following stages:for injection consists of the following stages:

Preparation of aseptic unit and the organization of work Preparation of aseptic unit and the organization of work in aseptic conditions. in aseptic conditions.

Preparation of vessels and auxiliary materials. Preparation of vessels and auxiliary materials. Preparation of solvents and drugs. Preparation of solvents and drugs. dissolved drugs. dissolved drugs. stabilization or isotones solutions stabilization or isotones solutions (if need)(if need) Quality control solutions. Quality control solutions. Filtering solutions to filling bottles, checking the Filtering solutions to filling bottles, checking the

absence of mechanical inclusions. absence of mechanical inclusions. closing, leak check, preparation for sterilization closing, leak check, preparation for sterilization

(marking). (marking). Sterilization. Sterilization. Quality control and design of drugs to dispense. Quality control and design of drugs to dispense.

Preparatory work 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.

DissolutionDissolution

Stability is achieved by adding stabilizers or use of special methods of preparation.

Stabilization solutions when necessaryStabilization solutions when necessary

AnalysisAnalysis

Filtering solutionsFiltering solutions

Corking bottlesCorking 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 minvolume from 100 to 500 ml- 12 minvolume 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 Stabilizers can be divided into three groups:groups:

substances which provide chemical substances which provide chemical stabilization - antioxidants that prevent stabilization - antioxidants that prevent oxidation. oxidation.

substances which prevent the substances which prevent the hydrolysis of saltshydrolysis of salts

Antiseptics providing microbiological Antiseptics providing microbiological stabilization. stabilization.

№ Name of matter which needs to stabilization

Stabilizator

1 Solutions 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 literNovocain of 0,25% - 3 ml a 0,1 M on 1 literNovocain of 0,5%- 4 ml a 0,1 M on 1 literNovocain of 1% - 9 ml a 0,1 M on 1 literNovocain of 2% - 12 ml a 0,1 M on 1 liter

2 Solutions of salts, formed by strong bases and weak acids (sodium nitrite, caffeine- benzoate of sodium, sodium thiosulphate, euphillin)

Sodium hydroxide (NaOH) 0.1 M10%, 20% caffeine- benzoate of sodium- 4 ml 0.1 M on 1 liter30% caffeine- benzoate of sodium- 20 ml 0.1 M on 1 liter

3 Solutions of easily oxidable substances (acid ascorbic, vicasol, sodium salicylate, streptocide, adrenalin hydrotartrat)

Streptocide 5%, 10% - sodium sulfit 2 g on 1 liter of solutionSodium salicylate 10% -sodium metabisulfite- a 1 g on 1 liter of solutionAcid ascorbic 5% - sodium metabisulfite- 2 g on 1 liter of solution

4 Solution 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 Pharmaceutics used antioxidants that slow oxidation and prevent the that slow oxidation and prevent the formation of active radicals. The most formation of active radicals. The most effective of them are phenols, effective of them are phenols, naftolnaftolumum, aminofenolum, aromatic , aminofenolum, aromatic amines.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 TECHNOLOGY stabilize ascorbic acid solutions introduction antioxidant stabilize ascorbic acid solutions introduction antioxidant

sodium metabisulfitis 1 g for liter or solution sodium sulphite sodium metabisulfitis 1 g for liter or solution sodium sulphite anhydrous 2 g for1 liter. anhydrous 2 g for1 liter.

In addition, solutions of ascorbic acid In addition, solutions of ascorbic acid strongly acidicstrongly acidic. In . In order to neutralize the environment of the sodium carbonate order to neutralize the environment of the sodium carbonate solution is introduced 23.85 g per 1 liter. solution is introduced 23.85 g per 1 liter.

In aseptic conditions in sterile volumetric flask dissolve In aseptic conditions in sterile volumetric flask dissolve 2.5 g of ascorbic acid, 1.19 sodium hydrogen carbonate and 2.5 g of ascorbic acid, 1.19 sodium hydrogen carbonate and 0.1 g anhydrous sodium sulphite in part 0.1 g anhydrous sodium sulphite in part freshly freshly prepared prepared water for injection. After the allocation of gas bubbles make water for injection. After the allocation of gas bubbles make up the solution to 50 ml, mixed, filtered in sterile bottles and up the solution to 50 ml, mixed, filtered in sterile bottles and sterilized at 120 ° C 8 min. Issuing labels "for injection", sterilized at 120 ° C 8 min. Issuing labels "for injection", "aseptically”."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 Hydrolysis of salts formed by weak base and strong acid, and their stabilization.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 120С 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 0,5Solutionis Аcidi hydrocarbonici 0,1 M gtts. VIIIV = 100 млSterilis Prepared: Signature Checked: Signature

Stabilization of glucoseStabilization of glucose

For stabilization glucose added stabilizer by Veybel’, prepare for the prescription:

Natrii chloridi 5.2 ml Natrii chloridi 5.2 ml Hydrochloric acid 4.4 ml Hydrochloric acid 4.4 ml Water for injection to 1 literWater for injection to 1 liter

When preparing glucose, regardless of its When preparing glucose, regardless of its concentration, stabilizer added 5% by concentration, stabilizer added 5% by

volume solution.volume solution.

THANK YOU FOR THANK YOU FOR ATTENTION!ATTENTION!