4_59832395819468GHBJJJHMUGHDGDFGSGTYS75217.pptx

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1. Physicochemical Drug Interactions and Incompatibilities TW

2. Drug–drug or drug– excipient interactions can take place before administration of a drug These may result in precipitation of the drug from solution, loss of potency or instability An incompatibility occurs when one drug is mixed with other drugs or agents, producing a product unsuitable for administration Reasons might be some modification of the effect of the active drug, such as an increase in toxicity or decrease in activity through some physical change such as decrease in solubility or stability TW

3. chelating – in which a chelator binds with a metal ion to form a complex adsorption to excipients and containers causing loss of drug interactions with plastics and loss of drug Protein binding to plasma proteins through which the free plasma concentration of drugs is reduced. TW

4. P H effects in vitro and in vivo In vitro pH effects P H changes often follow from the addition of a drug substance or solution to an infusion fluid . An increase or decrease in pH may then produce physical or chemical changes in the system: TW

5. Chemical, as well as physical, instability may result from changes in pH , buffering capacity , salt formation or complexation . Chemical instability may give rise to the formation of inactive or toxic products TW

6. In vivo pH effects Gastric effects Fluids have a pH of 1–3 in normal subjects Changes in the acid–base balance have a marked Influence on the absorption and thus on the activity of drugs Ingestion of antacids and food will change the pH of the stomach TW

7. Pharmaceutical Incompatibility, Containers & Closures TW

8. . Incompatibility is the result of mixing two or more antagonistic substances and it is detected by changes in physical, chemical or therapeutic qualities. It may affect the safety, efficacy and appearance of a medicine Classification 1. Physical 2. Chemical 3. Therapeutic TW

9. . Physical This can be expressed by: 1. Precipitation e.g. gums will precipitate in alcoholic solutions 2 . Color change e.g . change of color of alkaloids with PH change. 3 . Recrystallization To improve their pharmaceutical property crystalline forms may be converted to powder (non crystalline) form, but some substances may facilitate the recrystallization of the powdered form through time. 4. Leaching out of containers by some substances 5. Salting out – e.g. aromatic water + salt - The presence of salt facilitates the separation of the two phases TW

10. . Chemical This type of incompatibility is generally caused by PH change, decomposition reaction or complex formation. Can be expressed by: Precipitation Change of color Salting out Leaching TW

11. . Chemical incompatibility could be intentional or none intentional Intentional: - example - Production of CO 2 to produce effervescence. - effervescent granules Complexation between cyclodextrin and drugs - done for insoluble drugs to increase their solubility. TW

12. . Therapeutic Causes decrease in the efficacy or increase in the activity to toxic effect. Can be expressed by Synergistic effect Contra indication Adverse effect Synergistic : - One potentiates the activity of the other. Eg . Aspirin + Parcetamol TW

13. . Contraindication : - the opposite action may happen. Eg . Stimulant + hypnotic Adverse effect - drug may increase the adverse effect. So such drugs should not be given in combination TW

14. . Containers and closures Containers According to the USP, a container is “that which holds the article & is or may be in direct contact with the article .” The immediate container is “that is in direct contact with the article at all times”. The closure is part of the container TW

15. . Desirable properties The container must be rigid enough to prevent damage to the content. The material of construction must not react with the content. The closure must prevent Access of moisture Loss of moisture from creams and from water containing ointments and pastes Un intentional escape of the content and Entry of dirt or other contaminants such as odorous vapors that might cause tainting TW

16. . 4. The closure must be easily removed and replaced. 5. It must not be difficult to abstract the contents or to empty the container completely 6. For many products, protection from light must be given. 7. Medicaments or additives must not be absorbed by the container materials nor must diffusion through the walls be possible 8. It must be easy to label the container correctly. 9. It must have a pharmaceutically elegant appearance. TW

17. . Glass: - It has been widely used & continues to be the preferred packaging material for many pharmaceutical products. Advantages :- 1. Inert to most medicinal products 2 . Impervious to air & moisture 3. Allows easy inspection 4 . Can be colored to protect from harmful light. 5. Easy to clean & sterilize by heat 6. Available in different shaped containers TW

18. . Disadvantages :- 1. Fragile 2. Certain glasses may release alkali 3. Expensive compared to plastic 4. Heavy resulting in increased transport costs TW

19. . Constitution of official glass types Type General Description I highly resistant, Borosilicate glass , neutral II Treated soda lime glass (silica) III Soda – lime glass , silica (more leachable oxide). IV General purpose soda – lime glass with a low hydrolytic resistance . TW

20. . Example s :-Bottles, dropper bottles, jars, containers for parental products (Ampoules, vials) Plastics – can be used as container & carton (2 packaging). In recent times, it is used for packaging of parental products (infusion fluids & small volume injections) Advantag e :- Flexible & not easily broken - Low density & light in weight - Easily molded in to various shapes - Suitable for use as container, closure & as secondary packaging. - Cheap TW

21. . Disadvantage :- Not inert as type – I glass - Cracking & distortion with some chemicals - Some are very heat sensitive - Not impermeable to gas & vapor as glass. TW

22. Closures Any closure system should provide an effective seal to retain the container contents & exclude external contaminants. Child – resistance containers (CRCs) commonly consist of a glass or plastic vial or bottle with a specially designed closure . Closures are made of using natural rubbers or synthetic rubbers TW

23. . Injection containers are hermetic containers which are sterile used to hold preparations for parentral administration. A hermetic container is impervious to air or any other gas under the ordinary or customary conditions of handling shipment, storage & distribution. A single dose container is one in which the quantity of drug contained is intended as a single dose & when opened can’t be resealed. Ex. Ampoules , pre – filled syringes. TW

24. . A multiple – dose container is a hermetic container that permits withdrawal of successive portions of the contents without changing the strength, quality or purity of the remaining portion. Ex. Vials TW

25. . R e-packaging Is the process by which the dispenser transfer, a medication manually or automated system from manufacturers original container to another type of containers Repackaging is performed - In community pharmacy for dispensing purpose and in hospital pharmacy - Bulk medicines are repackaged into smaller quantities in dispensing containers for distribution to hospital wards, clinics and so on. TW

26. . The containers used in repackaging process must protect the product from Physical damage Chemical and microbial contamination Light, moisture and air (oxygen) Repackaging is limited for volatile drug Sterile products are not easily repackaged and require sterile procedure TW

27. . Material used for repackaging Glass bottles Plastic bottles Collapsible tubes Paper envelops Plastic envelops Paper has least value in primary packaging in term of maintaining safety, quality and stability of packaged drug In Ethiopia commonly used repackaging material is ordinary paper and also labeling is incomplete TW