Injection dosage form with stabilizers

1. Injection dosage form with stabilizers Author: as. Yu.Yu. Plaskonis

2. 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.

3. Injection solutions are prepared in aseptic unit

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

5. Technology process of preparation of 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 • 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 leave.

6. Preparatory work

8. Solutionspreparingbyvolumetric- mass in which medicines taken by weight, and solvent added to obtain the desired volume of solution.

9. Dissolution

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

11. Analysis

12. Filtering solutions

13. Corking bottles

14. Sterilization- solutions exposed within 1,5-2 hours after manufacture. The only exception is glucose, which sterilized immediately after production.

15. 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.

16. Stabilizers can be divided into three groups: • substances that provide chemical stabilization - antioxidants that prevent oxidation. • substances that prevent the hydrolysis of salts and esters saponification. • Antiseptics providing microbiological stabilization.

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

19. Oxidizing substances Oxidation are medicinal substances of different chemical structure: - derivatives of aromatic amines, fenotiazin, many salts of alkaloids, salts of bases, vitamins and other substances containing phenolic , alcohol, carbonyl groups, amino groups mobilize with hydrogen atoms.

20. Oxidation process can be slow in ways: • a) introduce a substance that rapidly reacts with alkil radicals, resulting in peroxide will become only part of the radicals; • b) enter the compound, which quickly reacts with peroxide radicals. This will reduce the rate of formation of peroxides and radicals regeneration; • c) enter Substances that Deplete hydro peroxide RООН.

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

22. 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. .

23. It is known that redox processes strengthened influenced by several factors such as the presence of heavy metal ions, pH value, oxygen, temperature, etc.

24. Stabilization easily oxidation substances are holding a set of measures: • Introduction of antioxidants (for binding oxygen). • Introduction of chelating agent (for binding heavy metal ions). • Creating boundaries pH optimum solution with acids (hydrochloric, citric, ascorbic). • Removal of oxygen in solvent and in the air above the solution (boiling, filling bottles to the top, saturating the solution with carbonic acid, filling bottles in current inert gas).

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

26. TECHNOLOGY stabilize ascorbic acid solutions introduction antioxidant sodium metabisulfitis 1 g per liter or solution or sodium sulphite anhydrous 2 g per 1 liter. In addition, solutions of ascorbic acid strongly acidic. In order to neutralize the environment of the sodium carbonate solution is introduced 23.85 g per 1 liter. Solution of sodium that is formed, askorbinat is pH 6-7. 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”.

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

28. 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.

29. 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.

30. Recommended stabilize hydrochloric acid solutions Apomorphini g / h, atropini sulfate, dybazoli, novocaine, spazmolityni, strychnine nitrate, cocaine g / s, dykayini. Stabilization of solution for injection, representing the salt of weak bases and strong acids by 0.1 M hydrochloric acid solutions. Examples are the solution of novocaine.

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

32. For stabilization the 0.5% solution of novocaine 0.1 M hydrochloric acid solution to pH 3,8-4,5 taking 4 ml per 1 liter of 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.

34. Hydrolysis of salts formed a strong base and weak acid These are solutions of caffeine-sodium benzoate, sodium thiosulfate, sodium nitrite.

35. In this case, hydrolytic processes enhanced in an acidic environment. To suppress hydrolysis is necessary: a weak alkaline medium by add-ing 0.1 M sodium hydroxide and adding sodium hydrogen carbonate. For stabilization of 1 liter of 10 and 20% solutions of caffeine-sodium benzoate SPh Ukraine X edition recommends adding 4 ml of 0.1 M sodium hydroxide and 30% sodium thiosulfate as a stabilizer is added sodium hydrogen carbonate (20 m per 1 liter).

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