Unit First.pptx

INORGANIC PHARMA CHEMISTRY

1. Unit-1 ACIDS, BASES AND BUFFERS

2. Limitations of L ewis As lewis acid base reactions involve electrons , they are expected to be very fast reactions . However there are many lewis acid-base reactions which are slow

3. Properties of Buffer solutions pH remain constant pH does not change on dilution pH doesn’t change even after addition of small quantities of acids or bases Constant pH: Useful in number of chemical reactions pH does not change on keeping for long time Buffer Solutions: Solutions that are able to resist the changes in pH values

4. Buffer capacity- Amount of acid/ Base that must be added to the buffer to produce a unit change of pH

5. Significance of Henderson- Hasselbalch equation pH of buffer solution can be calculated Dissociation constant of an acid ( pKa ) can be calculated Dissociation constant of an base ( pKb ) can be calculated

6. Applications of buffers in pharmacy Solubility - Solubility of compounds can be frequently controlled by providing a medium of suitable pH. Eg . Inorganic salts ( Phosphates )- soluble in acidic media and precipitate in basic media 2. Color- Color of many dyes are pH dependant Eg . Red color of cherry maintained at acidic pH

7. Applications of buffers in pharmacy (NR) 3. Stability of certain compounds Eg . Penicillin -unstable in alkaline pH 4. Some compounds structurally unstable at certain pH ranges Eg . Nitrites become brown in acidic media due to formation of nitrogen oxide 5. Patient comfort- Injectables / internal or external preparations are irritating if pH is different from normal

8. Applications of buffers in pharmacy 6. Medicinal compounds activity- Optimum pH is maintained Eg . Buffering methenamine with sodium dihydrogen phosphate 7. Analytical lab- buffers of known pH used as standard

9. General Principles for adjusting isotonicity and its importance Solutions for i/v injection : Approximate isotonicity is always desirable Solutions for s/c injection : Isotonicity is needed but it is not essential since they are injected into fatty tissues and not in blood stream Solutions for i/m injection: The aqueous solutions should be slightly hypertonic to promote rapid absorption

10. Solutions for intra-cutaneous injection : The parenteral preparations which are meant for diagnostic pupose should be isotonic in order to avoid false reaction Solutions for intrathecal injection: these must be isotonic, because volume of C.S.F (cerebrospinal fluid) is only 60 to 80 mL. Hence, a small volume of paratonic solution will disturb the osmotic pressure and may cause vomiting and other side-effects.

11. Solutions used for nasal drops: Isotonicity is needed, since paratonic solution may cause irritation Solutions used as eye drops and eye lotions: Eye lotion should be isotonic with lachrymal secretion, since a large volume is brought in contact with the eye. Eye drops may not be isotonic because only a small volume is used quickly get diluted by the lachrymal secretion.

12. Isotonicity –concept and importance Osmosis - Diffusion of solvent through a semi-permeable membrane from less concentrated solution to higher concentrated solution. Osmotic Pressure- The pressure needed to stop the osmotic flow [It stops the flow of solvent molecules from a dilute solution to a concentrated solution] Tonicity - Measure of the osmotic pressure of two solutions separated by a semi-permeable membrane

13. Isotonicity –concept and importance Isotonic solutions- A solution having the same solute concentration as in a cell/ Body fluid [A solution containing 0.9% NaCl is isotonic with blood plasma and is regarded as standard] Iso -osmotic solutions- Two solutions having the same osmotic pressure Paratonic solutions- Solutions which are not having the same osmotic pressure

14. Hypertonic isotonic Hypotonic NaCl 2% NaCl 0.9% NaCl 0.2% solute ‹ solute Inside outside solute = solute Inside outside solute › solute Inside outside shrinkage equilibrium swelling

15. Calculations for adjustment to isotonicity Based on Freezing point- % w/v of adjusting substance needed= (0.52-a)/b a= F.P of unadjusted solution b= F.P of 1% w/v solution of adjusting substance Based on molecular concentration % w/v of adjusting substance needed = (0.03M/N M= Gram molecular weight of the substance N= No. of ions into which the substance is ionized

16. Examples Q1. Find the concentration of sodium chloride required to make a 1 percent solution of boric acid, iso -osmotic with blood plasma. Given- The F.P of 1% w/v solution of boric acid is 0.288 °C. The F.P of 1% w/v solution of Nacl is 0.576 °C.

17. Q2. Find the concentration of Nacl required to produce a solution iso -osmatic with blood plasma.

18. Q3. Find the proportion of dextrose needed to form a solution iso -osmotic with blood plasma.

19. Q4. Find out the proportion of procaine hydrochloride which will yield a solution iso -osmotic with blood plasma F.P of procaine hydrochloride is 0.122

20. Impurities in Pharmaceutical substances

21. Types of impurities found in medicinal preparations Impurity: A compound is said to be impure if it is having foreign matter i.e impurities The impurities which are having a toxic effect when present beyond certain limits ( eg lead and arsenic salts) The impurities which otherwise are harmless but lowers the therapeutic activity of pure substance. The impurities which are able to lessen the keeping properties of the substance The impurities which are able to make the substance incompatible with other substances The impurities which can be easily detected by the senses like taste, odor, color or appearance ( eg . Sodium salicylate is usually discolored due to phenolic impurities)

22. Effects of impurities Impurities can be injurious when present above certain limits Impurities even present in traces may exert a cumulative toxic effect after a certain period If impurities are present in large proportions , they lowers the therapeutic activity of the substance Impurities may change the physical and chemical properties of the substance Impurities may bring about technical difficulties in the formulation Impurities may cause incompatibility with other substances Impurities may decrease the shelf life of the substance Impurities may change color, odor, taste etc.

23. Sources of impurities Raw materials employed in manufacturing For eg . Cu turnings are known to have iron and arsenic as impurities

24. 2. Reagents used in the manufacturing process For eg The solid precipitate is washed with water to remove excess of sodium carbonate and soluble chlorides as impurities

25. 3. Method or the process used in manufacture Reagents employed in the process- Soluble alkali in calcium carbonate arises from sodium carbonate b. Solvents - Tap water is having Ca 2+ ,Mg 2+ , Na + , Cl - ,SO4 2- , CO3 2- as impurities in very small amount

26. 4. Chemical processes used in the manufacture Tap water is used in various processes and has chloride, calcium and magnesium which may find access to the substance being manufactured 5 . Atmospheric contamination during the manufacturing process For eg . Sodium hydroxide absorbs atmospheric carbon dioxide

27. 6. Intermediate products in the manufacturing process- if the intermediate product KIO3 is not completely converted to KI, then it may be carried through to the final product as an impurity

28. 7. Defects in the manufacturing process If there is lesser heat or air or both , zinc metal is not completely converted into zinc oxide thus the final product ZnO may still contain metallic zinc as impurity

29. 8. Manufacturing hazards Particulate contamination Process errors Cross-contamination Microbial contamination Packing errors

30. 9. Storage conditions Filth Chemical instability Reaction with container materials Physical changes Temperature effects

31. 10. Decomposition of the product during storage Many organic substances get spoiled due to decomposition on exposure to the atmosphere eg amines, phenols

32. 11. Accidental substitution or delibrate adulteration with spurious or useless materials KBr may be adulterated with cheaper sodium bromide

33. LIMIT TESTS Limit tests are quantitative or semi-quantitative tests designed to identify and control small quantities of impurity which are likely to present in the substance

34. Limit test for Chloride Basic reaction: Soluble Chlorides Silver nitrate HNO3 Silver chloride Turbidity

35. Sample pass the limit test if turbidity of sample is less than the standard turbidity TEST SOLUTION STANDARD SOLUTION Specified substance (1g) + H20 (10mL) 0.05845 % w/v Solution of NaCl (1mL) Add HNO3 (1mL) Add HNO3 (1mL) Upto 50 mL (With H2O) Upto 50 mL (With H2O) Add AgNO3 (1mL) Add AgNO3 (1mL) Stirr and Kept aside for 5min, compare opalescence with standard Kept aside for 5min, compare opalescence with sample

36. Limit test for Sulphate Basic reaction: Dil HCL Soluble sulphates Barium chloride BaCL2 is replaced by BaSO4 reagent in IP (Modified limit test for Sulphate ) BaSO4 reagent- BaCl2 + Sulphate free alcohol+ Solution of potassium sulphate Sulphate free alcohol- Prevents super saturation and produce more uniform opalescence Potassium Sulphate - Increase sensitivity of the test

37. Sample pass the limit test if turbidity of sample is less than the standard turbidity TEST SOLUTION STANDARD SOLUTION Specified substance (1g) 0.1089 % w/v Solution of K2SO4 (1mL) Add HCL(2mL) Add HCL(2mL) Upto 45 mL (With H2O) Upto 45 mL (With H2O) Add BaSO4 reagent (5mL) Add BaSO4 reagent (5mL) Stirr and Kept aside for 5min, compare opalescence with standard Stirr and Kept aside for 5min, compare opalescence with sample

38. Limit test for IRON Citric acid In the ammonical alkaline medium Basic reaction Purple color Chelate because of Fe Colorless in acidic or neutralization solutions

39. Principle Iron in ammonical solution + Citric acid (20%) Doesn’t allow precipitation of iron by ammonia by forming a complex with it Eliminate interference of other metal cations + Thioglycollic acid Colorless, unpleasant odor More sensitive Pale pink to deep reddish purple color is formed due to ferrous compounds

40. Sample pass the limit test if color of sample is less dark than the color of standard TEST SOLUTION STANDARD SOLUTION Specified substance (1g) [ NaCl ] Standard solution of Iron/ Ferric ammonium sulphate i.e. 2mL [NH4Fe (SO4)2.12H2O], 0.173 g + HCL (1.5mL), Volume makeup upto 1000 mL using H2O Add water (40 mL) Add water (40mL) + 20% w/v Iron free citric acid (2mL) + 20% w/v Iron free citric acid (2mL) Add Thioglycollic acid (2drops) Add Thioglycollic acid (2drops) Made alkaline with Iron free ammonia Volume makeup upto 50 ml using water Allow to stand and compare with standard Made alkaline with Iron free ammonia Volume makeup upto 50 ml using water Allow to stand and compare with sample

41. Limit test for heavy metals [lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver, copper, molybdenum]

42. Sample pass the limit test if color of sample is less intense than the color of standard TEST SOLUTION STANDARD SOLUTION 25 mL of solution prepared for the test as directed in the individual monograph or dissolve the specified quantity of the substance under examination in a mixture of 20mL of water 20 ppm lead standard solution (1mL) Add dil NaoH (5mL) Add dil NaoH (5mL) Volume makeup Upto 50mL (H2O) Volume makeup Upto 50mL (H2O) Sodium sulphide solution (5drops) Sodium sulphide solution (5drops) Allow to stand for 5min and view downwards over a white surface Allow to stand for 5min and view downwards over a white surface

43. Limit test for Lead Expressed as parts of lead per million parts of the substance under examination

44. The color of the chloroform layer should not be more intense than standard solution

45. TEST SOLUTION STANDARD SOLUTION Transfer sample solution into separator/ separating funnel 1 ppm lead standard solution Add Ammonium citrate solution Sp. (6mL) * For Iron salts (10mL) Add Ammonium citrate solution Sp. (6mL) * For Iron salts (10mL) Hydroxylamine Hydrochloride solution Sp. (2mL) Hydroxylamine Hydrochloride solution Sp. (2mL) Phenol red solution (2drops) Make solution alkaline and red in color (Strong ammonia solution) Potassium cyanide solution Sp. (2mL) Extract the above solution with dithizone solution (5 ml for each time)until the dithizone extraction solution retain it become green 1% v/v Nitric acid (30mL) Discard the chloroform layer Shake the combine dithiazone solution for 30 seconds Dithizone solution (5mL) and shake for 30 seconds Phenol red solution (2drops) Make solution alkaline and red in color (Strong ammonia solution) Potassium cyanide solution Sp. (2mL) Extract the above solution with dithizone solution (5 ml for each time)until the dithizone extraction solution retain it become green 1% v/v Nitric acid (30mL) Discard the chloroform layer Shake the combine dithiazone solution for 30 seconds Dithizone solution (5mL) and shake for 30 seconds

46. Limit test for Arsenic Indicated in terms of ppm i.e parts of arsenic as per million parts (by weight ) of the substance Apparatus: Conical flask closed with stopper through which passes a lower glass tube ( insert 50-60mg of lead acetate cotton) A second glass tube is placed in contact with the first and is held in position by clips Between the flat surfaces of the tubes place a disc of mercuric chloride

47. TEST SOLUTION STANDARD SOLUTION Test solution 10 ppm Arsenic standard solution diluted to 50ml water (1mL) Add 1M KI (5mL) + Zinc AsT (10g) Add 1M KI (5mL) + Zinc AsT (10g) Assemble the apparatus, immerse the flask in water bath at a temperatures such that a uniform evolution of a gas is maintained Assemble the apparatus, immerse the flask in water bath at a temperatures such that a uniform evolution of a gas is maintained After 40min any stain on the mercuric chloride paper should not be more intense than the standard solution After 40min any stain on the mercuric chloride paper should not be more intense than the standard solution