Slide 2: STABILITY Slide 3: PRESENTED BY
ABIKESH PRASAD KUMAR MAHAPATRA
1ST SEMESTAR STABILITY STUDIES OF DRUG PRODUCT Drug stability : Drug stability Definition:-
Stability of a pharmaceutical product may be defined as the capability of a particular drug dosage form to maintain its chemical , physical, and therapeutical integrity against the microbial contamination in a specific container closure system
Stability is officially defined as the time lapse during which the drug product retains the same properties and characteristics that it possessed at the time of manufacture.
The stability of a product is expressed as the expiry period or technically as shelf life. OBJECTIVE OF STABILITY STUDY : OBJECTIVE OF STABILITY STUDY To gather information during preformulation stage to produce a stable product.
To determine maximum expiration date.
To gate an idea of storage condition.
To determine the packaging components.
The retest period of pharmaceuticals.
Transport conditions. APPLICATION OF STABILITY STUDIES IN PHARMACEUTICALS : APPLICATION OF STABILITY STUDIES IN PHARMACEUTICALS Chemical degradation of active drug may reduce the quantity of therapeutic agent in the dosage form .Drugs having narrow therapeutic indices like 5-fluro uracil, carbamazepine etc have very small therapeutic range. Slight degradation of drug may produce sub therapeuti concentration.
After degradation a drug may produce more toxic product(s) which may be more toxic than the parent product.
Instability of drug product reduce bioavailability .This may be caused by physical or chemical instability.
Instability of a product may change the physical appearance of the product. Factors affecting stability study : Factors affecting stability study Storage time
Type of dosage form
Container and closure system Slide 8: The design of the stability programme for the finished product based on the knowledge of the drug substance and experienced gained from clinical formulation study & stability study.
It should stated the storage condition and the rational change in the dosage form. Different steps involved : Different steps involved Selection of batches
Test procedure & test criteria
Storage test condition
Statements & labeling Test procedure & test criteria : Test procedure & test criteria It must covers those features which are susceptible to change during storage & likely effect quality,safty & efficacy.
Analytical procedure should be fully validated and the should be stability indicating.
The testing not only include chemical & biological stability but also loss of preservative,physical. Organoleptic properties & also microbiological attributes.
Preservative efficacy testing should done on stored sample. Specification : Specification Specification is a list of
Tests & test attributes
Reference to analytical procedure
Acceptance criteria Testing Frequency : Testing Frequency Long term studies
Generally minimum three time points
Intermediate storage condition studies
Minimum four time points
Eg:-0,6,9,12 months Storage test condition : Storage test condition ICH guide lines for storage conditionAccording to the ICH guideline different standard storage conditions are Climate zone I :Great Britain, North Europe, Russia, Canada. Climate zone II :US, Japan, South Europe Climate zone III :Iran, Iraq, Sudan, Climate zone IV :Brazil, Ghana, Indonesia, Philippins. *India comes under climatic zones III & IV. : ICH guide lines for storage conditionAccording to the ICH guideline different standard storage conditions are Climate zone I :Great Britain, North Europe, Russia, Canada. Climate zone II :US, Japan, South Europe Climate zone III :Iran, Iraq, Sudan, Climate zone IV :Brazil, Ghana, Indonesia, Philippins. *India comes under climatic zones III & IV. Storage condition in accordance with ICH Q1A (R2) &Q1F : Storage condition in accordance with ICH Q1A (R2) &Q1F Where significant changes occour due to accelerated testing additional testing at an intermediate condition 30 oC + 2 oC / 60 ± 5 % RH should be significant.
According to ICH significant change in drug product are
A 5% change in assay value from initial
Any degradation product exceeds its set limits.
Failure to meet acceptance criteria.
The pH value and the dissolution no longer satisfies the requirement. Drug substances intended for storage in a refrigerator : Drug substances intended for storage in a refrigerator Evaluation : Evaluation A systematic approach should be adopted in the presentation and evaluation of the stability information which covers the physical,chemical & biological parameter.
A minimum of 3 batches of drug product was tested.
The analyst must found the batch to batch variability & if it is small than only it is accepted & it can be done by different statistical test's ( P value for level of significance for rejection).
Where the data shows so little degradation & so little variability that is apparent from looking the data that the requested shelf life will be granted. & it is normally unnecessary to go through the formal statistical analysis.
Any evaluation also consider the not only the essay but also consider the other parameter testing & also the different stability and degradation performance.
The stability of the drug product after reconstitution or diluting according to labeling ,should be addressed to provide appropriate and supportive information. REFERENCES : REFERENCES Dr. Ali Javed,Khar R.K,Ahuja Alka,Text book of dosage form design,Birla publication,2004,page110-113.
Lachman leo,Liberman .A.Hebert,Kanig L,The theory and practice of industrial pharmacy,Varghese publishing house,3rd edition,page-856-858.
Yoshioka Sumie, Stella J,Stability of drugs and dosage forms,springer international edition,2006,page-139-145
Indian journal of Pharmaceutical Education,vol-38,dec-2004,page-194-198