Commentaires

Diaporama

Plan

1	Drug Stability Associate Professor D E Moore
2	Degradation of Drug Dosage Form Loss of potency - lessens therapeutic effect Drug degrades to a toxic substance Degradation leads to aesthetically unacceptable product - change in colour, formation of bad odour and/or taste Stability in GIT important for absorption of correct form of the drug
3	Drug degrades to a toxic substance
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5	Chemical Degradation of Pharmaceuticals Hydrolysis Oxidation Isomerization Epimerization Reduction Polymerization
6	Physical Degradation of Pharmaceuticals Solubility changes Crystal growth Emulsion cracking Protein denaturation Phase separation Packaging failure
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8	First order kinetic determination
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11	The effect of temperature
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14	Accelerated Stability Testing
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16	Government Requirements: Stability Testing for New Drug Formulations
17	STABILITY TESTING PROTOCOL
18	Drug Degradation by Hydrolysis
19	Hydrolysis reactions are strongly affected by pH
20	METHYL PARABEN (p-Hydroxybenzoic acid methyl ester) at 130^oC
21	ASPIRIN pH-Rate Profile at 25^oC
22	pH of Maximum Stability
23	Drugs susceptible to Hydrolysis - Esters
24	Drugs susceptible to Hydrolysis - Amides
25	Sulfonamides
26	Chlordiazepoxide
27	Moisture Sources Environment during formulation and packaging product absorption transmission through package additional internal packaging imperfections in the seal (most important source)
28	Precautions to avoid moisture absorption
29	Sorbents and Dessicants Activated clays / zeolites Silica gel Molecular sieve Calcium oxide
30	Methods for use of Dessicants and Sorbents
31	Water Absorbers (Dessicants) Silica gel Silicon dioxide pure, porous, amorphous chemically inert, non-toxic, resists attrition high capacity > 40% RH low capacity < 40% RH fair capacity > 32^oC impregnation with CoCl₂: colour change most common Activated clay Mined and processed variation in properties Oxide of silicon, aluminium, iron and magnesium fair absorption capacity at low RH poor capacity >32^oC inexpensive specific applications
32	Sorbents Activated carbon adsorbs organic compounds can be combined with desiccants or oxygen absorbers non-toxic can be formulated with pharmaceuticals Ferrous based materials absorb oxygen irreversible reaction
33	Containers Leaching release of components of container into contents increased by increased temperature agitation polymer additives
34	Containers ability to protect well closed tight hermetic airtight sealed headspace number of doses single dose multidose tamper evident child resistant
35	Protection Mechanical hazards shock or impact compression vibration abrasion puncture Biological hazards microbes vermin humans Environmental hazards moisture temperature pressure light gases Chemical hazards adsorption absorption and loss leaching detachment of container