Lecture 1 Introduction to Drug Stability PDF

Lecture 1 INTRODUCTION  DRUG STABILITY Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container to remain within its physical, chemical, microbiological therapeutic and toxicological specification.S.E. Stability of...

Lecture 1 INTRODUCTION  DRUG STABILITY Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container to remain within its physical, chemical, microbiological therapeutic and toxicological specification.S.E. Stability of drug also can be defined as the time from the date of manufacture and packaging of the formulation until its chemical or predetermined level of labelled potency and its physical characteristics have not changed appreciably. S.E The USP defines the stability of pharmaceutical product as “extent to which a product retains within specified limits” and throughout its period of storage and use(i.e its shelf life) the same properties and characteristics that it possessed at the time of its manufacturer’’S.E Assurance that the packed product will be stable for its anticipated self life must come from an accumulation of valid data on the drug in its commercial package. These stability data involves selected parameters that taken together from the stability profile. Pharmaceutical products are expected to meet their specification for identifying purity, quality and strength throughout their defined storage period at specific storage condition.(√ or X) The stability of pharmaceutical product is investigated throughout the various stages of the development process..(√ or X) The stability of the drug substance is first assessed in the preformulation stage..(√ or X) At this stage, the pharmacist determine the drug substance.Stability/ compatibility with various solvents, buffered, solutions, and excipents considered for formulation developments  Optimization of the stable of formulation of a pharmaceutical product is built upon the information obtained from the performulation stage and continues during the formulation development stages..(√ or X)  Once a pharmaceutical product has gained regulatory approved and is marketed, the pharmacist must understand the proper storage and handling of the drug. There are five types of stability that must be consider for each drug WHY STABILITY ? Provide a evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as….. temperature, Humidity and light. Establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions. Because physical, chemical or microbiological changes might impact the efficiency and security of the final product. MENTION Stability Studies are preformed on... Drug Substances (DS)  The unformulated drug substance that may subsequently be formulated with excipients to produce the dosage form. Drug Products (DP)  The dosage form in the final immediate packaging intended for marketing……. controlled and documented determination of acceptable changes of the drug substance or drug product What are changes? Physical changes Appearance Melting point Clarity and color of solution moisture Crystal modification (Polymorphism) Particle size  Chemical changes Increase in Degradation Decrease of Assay  Microbial changes Drug Stability and Stabilization Techniques Ideally any commercial pharmaceutical product should have a shelf life of 3 yrs and should not fall below 90-95% potency under recommended storage..(√ or X) In designing a solid dosage form it is necessary to know the inherent stability of the drug substance, excipients to be used, formulation procedure..(√ or X) For a drug substance, we need to study 3 categories of stabilities- 1. Solid state stability of drug only 2. Compatibility studies ( drug+ excipients ) 3. Solution phase stability (CHOOSE) 1. SOLID STATE STABILITY It includes both physical and chemical stability Physical changes caused by Polymorphic transitions and Hygroscopicity..(√ or X) Chemical changes such as solvolysis, oxidation, photolysis, pyrolysis..(√ or X) Examination of the chemical structure, Example- presence of unsaturation makes the compound susceptible to free radical mediated or photocatalyzed oxidation. PHYSICAL CHANGES/INSTABILITY 1. Solubility 2. pKa 3. Melting point 4. Crystal form 5. Equilibrium moisture content. Example- amorphous materials are less stable than their crystalline counterparts. A relatively dense material may better withstand ambient stresses amino benzyl penicillin trihydrate is more denser and stable than its amorphous form. CHEMICAL CHANGES/INSTABILITY Solid state reactions are generally slow and it is customary to use stress conditions in investigation of stability. Data obtained under stress is then extrapolated to make prediction of stability. High temperature can drive moisture out of a sample and render the material apparently stable otherwise prone to hydrolysis..(√ or X) Example- Above 65% relative humidity the beta form of chlortetracycline hydrochloride transforms into alpha form.  CHEMICAL DEGRADATION STUDY Hydrolysis- usually drugs such as esters, amides and lactams undergo hydrolysis. Oxidation Reduction- loss of electrons, gain of electrons. Auto oxidation also is responsible. Eg-tetracyclines, vit A, vit D, morphine. Photolysis- Compounds such as ascorbic acid, riboflavin, cyanacobalamine, folic acid undergo degradation on exposure to light. Sometimes coupled with thermal reactions. Isomerisation-Compounds get converted into a less effective form. Eg-Adrenaline solutions at low pH lose activity since its levo form is more stable than dextro form DISCUSS ELEVATED TEMPERATURE STUDIES Tests are usually performed at 40 ,50 ,600C in conjuction with ambient humidity..(√ or X) OR CHOOSE Higher temperatures are also used, samples kept at highest temperature examined for chemical and physical changes at weekly intervals- if no change is seen after 30 days at 600C Stability prognosis is excellent..(√ or X) Arrhenius Treatment is used to determine the degradation rate at lower temperature Thank you