3. Incompatibility full.pptx Pharmaceutics II

3. Incompatibility full.pptx

1. Second Year Diploma in Pharmacy Pharmaceutics II (0811) Chapter – 2. incompatibility in prescription Prof. Vaishali P. Argade Lecturer in PRES, Institute of Pharmacy, Loni Email:[email protected] 1

2. Learning Outcomes After completion of this video, you will be able to: Understand the concept of Incompatibility Understand the reasons of Incompatibility Classify the Incompatibility Understand the concept of Physical, chemical & therapeutic Incompatibility with example. 2

3. Definition Incompatibility is an undesirable result of mixing of two or more antagonistic substances which may affects the safety efficacy and appearance of the pharmaceutical dosage forms. 3

4. Incompatibility may be due to Drug-Drug Incompatibility 1 st Drug + 2 nd Drug Mixed Undesired / unwanted Product Drug-Drug Incompatibility 4

5. Incompatibility may be due to Drug Excipient Incompatibility Drug + Excipients Mixed Undesired / unwanted Product Drug Excipient Incompatibility 5

6. Incompatibility may be due to Dosage Error Incompatibility Example: Rx Codeine Phosphate 5 g Prepare 10 powders 6 Rx Codeine Phosphate 5 mg Prepare 10 powders Correct Prescription Dosage Error Incompatibility

7. Incompatibility may occur not only during compounding & dispensing but also at any stage during formulation, Manufacturing, Packaging & administration of drugs. Now a days the prescription are generally written for the official (generic) or proprietary(Trade/Brand) names which are manufactured by pharmaceutical companies. 7

8. Types of Drug Incompatibility 1. Physical incompatibility 2 . Chemical incompatibility 3. Therapeutic incompatibility 8

9. Definition Physical Incompatibility When two or more than two substances combined together a physical changes take place and an undesirable product is formed it is called as physical incompatibility. It is due to insolubility, immiscibility, precipitation , liquefaction of solid materials . 9

10. General methods of Correction of Physical Incompatibility Change the order of mixing of ingredients in prescription By Emulsification Addition of suspending agents Change in the forms of ingredients By addition, substitution or Omission of therapeutically inactive substances 10

11. Example of Physical Incompatibility with there methods of correction Example 1: Immiscibility Rx Castor Oil 15ml Water up to 60ml Make an Emulsion In this prescription castor oil & water are immiscible with each other. To overcome this incompatibility an emulsifying agents is used to make a good emulsion. 11

12. . Example 2:Insolubility Insolubility means the inability of material to dissolve in a particular solvent. Majority of Physical incompatibility are due to Insolubility of organic or inorganic compounds in to a particular solvent. Some solids are insoluble in solvent there are of two types: Diffusible Solids B) Indiffusible Solids 12

13. A) Diffusible Solids: These are insoluble in water but get evenly distributed on shaking throughout the liquid for sufficient long time. Eg : Magnessium carbonate B) Indiffusible Soilds : These are insoluble in water but do not get evenly distributed on shaking throughout the liquid for sufficient long time, So Suspending agents are incorporated. This suspending agents increases the thickness of the preparation and maintained the uniform distribution of insoluble substances. Eg : Chalk powder, Acetyl salicylic Acid, Phenacetin , Zinc Oxide & Calamine etc. 13

14. Incase of Indiffusible solids Two types of suspending agents are added, Compound Tragacanth Powder ( 2g/100ml), CTP: It is used when vehicle is other than water or Chloroform water b) Tragacanth Mucilage (1/4 th of it’s total volume), TM: It is used when vehicle is Water or Chloroform water 14

15. Rx Phenacetin 3g Caffeine 1g Orange Syrup 12ml Water up to 90ml Make a Mixture In this prescription Phenacetin is a indiffusible substances so, suspending agents are used to make a stable mixure . 15

16. Example 3: Precipitation When the drug is insoluble in the vehicle it may be precipitated Eg : Resins are insoluble in Water When tincture containing resinous matter is added in water , resins agglomerated forming indiffusible precipitate. Rx Tincture benzoin compound 5ml Glycerine 15ml Rose water up to 100ml Tincture benzoin compound contain resins which may be precipitated when combined with water. So addition of tincture with rapid stirring yields a fine colloidal dispersion. So there is no need of suspending agent. 16

17. Example 4: Liquefaction When certain low melting points solids (Ex: camphor, Phenol, Menthol, Thymol , Chloral hydrate, Aspirin) are mixed together a liquid or semisolid mass is formed known as Eutectic mixture . This is due to lowering of melting points of the mixture to below room temperature. This types of substances create problems when they are dispense in powder form so, such types of substances can be dispensed as follows: Dispense a separate powder Low melting point substances triturate together to form a liquid. Add absorbent like light kaolin or light magnesium carbonate to produce a free flowing powder. The individual medicament weigh separately & mixed with absorbent lastly combined together then filled in to a suitable container. 17

18. Rx Menthol 5g Camphor 5g Ammonium Chloride 30g Light Magnessium Carbonate 60g Make an insufflation In this prescription Menthol, Camphor & Ammonium Chloride get liquefied on mixing with each other. To dispense this prescription Menthol, Camphor & Ammonium Chloride are triturate together to form a liquid. Add light magnesium carbonate & mixed it thoroughly to make a free flowing powder. 18

19. 2. Definition C hemical I ncompatibility When two or more than two substances combined together a Chemical interactions take place and an undesirable product is formed it is called as chemical incompatibility. Types of C hemical Incompatibility Tolerated : In this type, the chemical interaction can be minimize by changing the order of mixing but not alteration made in the formulation. Adjusted : In this type, the chemical interaction can be minimize by addition or substitution of one of the reacting substance with another of equal therapeutic value . 19

20. The Chemical Incompatibility is may be due to; Intentional: When the prescriber knowingly prescribe the incompatible drugs is called the intentional chemical incompatibility. 2. Un-Intentional : When the prescriber Unknowingly prescribe the incompatible drugs is called the Un-intentional chemical incompatibility. 20

21. Precipitate Yielding Interactions There a re two methods for dispensing of diffusible & indiffusible solids; Method A: Method B: Method A : Use when diffusible precipitate is formed. Divide the vehicle in to two equal portion. Dissolve one of the reacting substance in one portion of the vehicle & second reacting substance with second portion of the vehicle. Lastly slowly add one portion in to the another with rapid stirring. 21 Fig. 1: Flow chart for explaining Method A Rx Sodium hydroxide 2g Sodium chloride 2g Water q.s . 100ml

22. Method B: Use when Indiffusible precipitate is formed. Divide the vehicle in to two equal portion. Dissolve one of the reacting substance in one portion of the vehicle. Weight a suitable quantity of Compound tragacanth powder/ Tragacanth Mucilage & transfer in to mortar, to it add second portion of the vehicle to produce smooth mucilage then add second reacting substance. Lastly mixed two portion by slowly adding one portion in to the another with rapid stirring. 22 Fig. 2: Flow chart for explaining Method B Rx Sodium hydroxide 2g Sodium chloride 2g Water q.s . 100ml

23. Example of c hemical incompatibility with there methods of correction Alkaloidal Incompatibility a) Alkaloidal salts with alkaline substances b) Alkaloidal salts with soluble iodides c) Alkaloidal salts with Tannins d) Alkaloidal salts with Salicylates e) Alkaloidal salts with soluble iodides & Bromides 2. Soluble Salicylate incompatibility a) Soluble salicylate with ferric salts b) Soluble salicylate & benzoate with acid c) Soluble salicylate with Alkali bicarbonates 3. Soluble iodides incompatibility a) Oxidation of iodides with ferric salts b) Oxidation of iodides with Potassium chlorate c) Oxidation of iodides with Quinine Sulphate 4. Chemical Incompatibility causing evolution of carbon dioxide a) Sodium bicarbonates with soluble calcium & magnesium salts b) Sodium bicarbonates with soluble calcium & magnesium salts 5. Miscellaneous chemical incompatibility a) Potassium Chorate with Oxidisable Substances: b) Soluble barbiturate with ammonium bromide c) Incompatibility of Liquorice Liquid extract 23

24. 1. Alkaloidal Incompatibility Alkaloidal salts with alkaline substances Alkaloids are very slightly soluble in water where as alkaloidal salts are soluble in water. When this alkaloidal salts are reacts with alkaline substances Diffusible precipitate is formed. Hence follows method A for precipitate yielding interaction. Rx Strychnine Hydrochloride solution 6ml Aromatic sprit of Ammonia 4ml Water up to 120ml Make a Mixture 24

25. 25 Fig. 3: Flow chart for explaining example using Method A

26. b) Alkaloidal salts with Soluble iodide Eg : When Strychnin is prescribe with pottassiun iodide insoluble hydroiodide is formed which is diffusible ppt Hence follow methods A for ppt. yielding interactions. C) Alkaloidal salts with Tannins 26

27. d) Alkaloidal salts with Salicylates Example Rx Quinine Hydrochloride 0.12g Sodium Salicylate 4 g Water up to 100ml Make a Mixture In this Prescription, 27

28. 28 Fig. 4 : Flow chart for explaining example using Method B

29. e) Alkaloidal salts with soluble iodides & Bromides 29 Hence follows method A for precipitate yielding interaction

30. Rx Potassium iodide 1.5g Tincture of Stramonium 8.5 ml Chloroform Water 100ml In this prescription Tincture of Stramonium combined with Potassium iodide it will formed a diffusible ppt . of hydroiodides so follow method A for Precipitate yielding interactions 30

31. 31 Fig. 5: Flow chart for explaining example using Method A

32. Example Rx Quinine Sulphate 1.5g Dilute Sulphuric Acid 4 ml Patassium iodide 8 g Water q.s . 200ml In this Prescription Dilute the Dilute Sulphuric Acid with 100 ml of water & dissolved Quinine Sulphate in it. Patassium iodide is dissolved in remaining quantity of water & mixed with the first portion. The mixture formed is point clear at first time but after about 3 days it may deposit bronze or olive green scale due to herapath reaction for quinine. 32

33. 2. Soluble Salicylate incompatibility Soluble salicylate with ferric salts 33 Example Rx Ferric Chloride Solution 2ml Sodium Salicylate 3g Water q.s . 90ml Make a Mixture In this Prescription

34. b) Soluble salicylate & benzoate with acid 34 Example Rx Sodium Salicylate 3 g Syrups of Lemon 15ml Water q.s . 60ml Make a Mixture In this Prescription Syrup of lemon contains citric acid when it react with Sodium Salicylate it gives Salicylic Acid as indiffusible ppt. T o correct this follows method B for precipitate yielding interactions or replace the lemon syrups with simple syrups.

35. c) Soluble salicylate with Alkali bicarbonates Soluble salicylate & Alkali bicarbonates combined together, it absorb the atmospheric oxygen & become reddish brown in color this color change does not affect the therapeutic value but may leads to confusion in the mind of patient. To avoid such confusion antioxidants like sodium metabisulphite is added with permission of the doctor. Example Rx Soluble salicylate 8g Sodium bicarbonates 8g Sodium Metabisulphite 0.08g Chloroform Water q.s . 120ml Make a Mixture 35

36. 3. Soluble iodides incompatibility Oxidation of iodides with ferric salts When ferric salts reacts with soluble iodides it get converted in to ferrous salt. To prevent this incompatibility , the prescriber may substitute ferric salts with iron & ammonium citrate. Ultimately the iron is converted in to an organic compound which does not yield ferric ions. b) Oxidation of iodides with Potassium chlorate When soluble iodides reacts with Potassium chlorate free iodine is liberated. To prevent this incompatibility the two reacting substance dispensed separately. 36

37. c) Oxidation of iodides with Quinine Sulphate Quinine Sulphate is not freely soluble in water, to make it soluble dilute Sulphuric acid is used. These Sulphuric acid liberates hydriodic acid from patassium iodide. Hydriodic acid is partially oxidized by Sulphuric acid & gives iodine . The iodine, hydriodic acid & Quinine Sulphate then combined to formed a compound called as Herapathite or Iodosulphite of quinine. The compound has following chemical formula: ( C 20 H 24 O 4 N 2 ) . 3H 2 S O 4 . 2HI. 2I 2 . 6H 2 The mixture formed is clear at first but after about 3 days it may deposit bronze or olive green scale due to herapath reaction. 37

38. These incompatibility can be removed by one of the following methods; Refer the prescription back to the prescriber Supply the preparation sufficient for about 3 days only. In case the patient required the mixture for more than three days both the solutions are supplied in the separate bottle. Tell the patient regarding bronze or olive green color change. 38

39. Example Rx Quinine Sulphate 1.5g Dilute Sulphuric Acid 4 ml Patassium iodide 8 g Water q.s . 200ml In this Prescription Dilute the Dilute Sulphuric Acid with 100 ml of water & dissolved Quinine Sulphate in it. Patassium iodide is dissolved in remaining quantity of water & mixed with the first portion. The mixture formed is point clear at first time but after about 3 days it may deposit bronze or olive green scale due to herapath reaction for quinine. 39

40. 4. Chemical Incompatibility Causing Evolution of Carbon dioxide When carbonates and bicarbonates are dispensed in the presence of acidic drugs they react together with evaluation of carbon dioxide. If the reaction is not allowed to complete there may be a chances of bursting of the bottle. To prevent these bursting, the reaction must be completed before transferring the mixture in to dispensing bottle. Hot water can also be use to increased the rate of reaction. 40

41. Sodium bicarbonates with soluble calcium & magnesium salts When Sodium bicarbonates combined with soluble calcium & magnesium salts , due to double decomposition reaction carbon dioxide is formed along with insoluble carbonates which is a diffusible ppt. These reaction is slow at room temperature so use hot water to increase the rate of reaction. This mixture is dispensed when effervescence is ceased. The precipitation of carbonate formed are diffusible in nature hence follow method A for precipitate yielding interactions. 41

42. b) Bismuth subnitrate with sodium bicarbonate Bismuth subnitrate when combined when combined with sodium bicarbonate in the presence of water, carbon dioxide gas is liberated due to the following reaction. 42

43. 5. Miscellaneous Chemical Incompatibility a) Potassium Chorate with Oxidisable Substances: When potassium chlorate is prescribed along with oxidisable substances charcoal, sulphur sugar organic compound or any oxidisable substance, during dispensing if heating /trituration is done there are chances of explosion . To avoid this ingredients should be powdered separately in dry mortar & mix gently with clean spatula on ointment tile,without any friction. 43

44. b) Soluble barbiturate with ammonium bromide When Soluble barbiturate combined with ammonium bromide in the presence of water the baritone is separated as indiffusible precipitate which are insoluble in water. Hence follow method B for precipitate yielding interaction. C) Incompatibility of Liquorice Liquid extract Liquorice Liquid extract is used as a flavouring agent. The flavouring property is due to glycerrhizine which is a mixtue of potassium & calcium salts of glycerrhizinic acid. The acid decomposes & formed a diffusible ppt. Hence follow method A for precipitate yielding interaction or the prescription may referred back to the prescriber for the change of flavoring agent. 44

45. Definition 3. Therapeutic Incompatibility Therapeutic Incompatibility may be a result of prescribing certain drugs to produces a specific degree of pharmacological action but the nature or intensity of action produced is different from that intended by the prescriber . Therapeutic Incompatibility may be due to following reasons: 1) Error in dosage 2) Wrong n ame or dosage form 3) Contra-indicated drugs 4) Synergistic & Antagonistic drugs 5) Drug Interaction 45

46. 1. Error in dosage: It is the most serious type of error in dispensing so, it is the duty of pharmacist to check the prescription before dispensing. Rx Codeine Phosphate 0.5 g Prepare 10 powders This is an example of over dosage. The intension of physician may be to prescribe 5 mg but he has given 0.5 g (500mg). In this case refer the prescription back to the prescriber for correction of over dosage of Codeine phosphate. 46

47. 2. Wrong name or dosage forms: Certain drugs have quite similar names like Prednison & prednisolon , Digoxin & Digitoxin so it may create a problem during dispensing. Many times drugs are available in different dosage forms and hence it is necessary to mention the dosage forms of a drugs. 3. Contra-indicated drugs Certain drugs are contraindicated in particular patient whom are allergic to it. Eg : Penicilline & Sulpha drugs are contraindicated in patients who are allergic to it. So in this case refer prescription back to the prescriber for correction. 47

48. 4. Synergistic & antagonistic drugs Synergism: Example Rx Amphetamine Sulphate 20mg Ephedrine sulphate 100mg Syrups q.s . 100ml Make a Mixture In this combination Amphetamine sulphate & Ephedrine sulphate are sympathomimetic drugs so there is need to reduced the dose of each drugs or refer the prescription back to the prescriber for correction. 48

49. Antagonism : Example Rx Acetyl salicylic acid 0.6g Probenicid 0.5 g Acetyl salicylic acid & Probenicid are used in the treatment of gout but the combination of these two drugs leads to neutralization so, refer the prescription back to the prescriber for correction . 49

50. 5. Drug Interaction When two or more drugs are administered together effect of one drugs is alter by the simultaneous administration of another drug. Example Rx Tetracycline hydrochloride 250mg Prepared 10 capsules Direction:Take 1 capsule every six hour with milk Tetracycline is inactivated by calcium which is present in milk so tetracycline capsules should not be given with milk so, refer the prescription back to the prescriber for correction or change the direction take 1 capsule every 6 hours with water. 50

51. References Pharmaceutics II By R. M. Mehata , Vallabh Prakashan , Third edition, 2010. Pharmaceutics-2 (Dispensing Pharmacy) By Dr. G.K.Jani , B.S.shah Prakashan , 10 th edition, 2011-2012. Introduction to Pharmaceutics-II By A.K.Gupta & S.S. Bajaj, CBS Publishers & Distributors, 4 th edition,2000. MSBTE board Annual question paper, https ://msbte.org.in 51 By- Ms. Argade V.P.

52. Thank You ..... 52