Stability study

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Stability study: Basic concepts and objectives:

Stability study: Basic concepts and objectives Guided by: Dr. R.K. Parikh Department of Pharmaceutical technology and Pharmaceutics, L.M. College of Pharmacy, Ahmedabad. Presented by: Suresh Khasiya-06 Soham D. Sheta-18 Smeet Shah-17 M-Pharma-1 2011-2012


Contents Introduction Regulation and guidances Types of stability study What happens due to instability? Objectives References 2 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Introduction Stability is defined as the capacity of a drug substance or drug product to remain within the established specifications to maintain its identity, strength, quality and purity through out the retest or expiration dating period . The purpose of stability testing is to provide 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. 3 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

Stability studies are incorporated at all stages of the drug product life cycle – from early stages of product development to late stage follow-up stabilities. In particular the life cycle can be segregated into 6 different stages: :

Stability studies are incorporated at all stages of the drug product life cycle – from early stages of product development to late stage follow-up stabilities. In particular the life cycle can be segregated into 6 different stages: Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 4 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

Regulations and Guidances:

Regulations and Guidances The ICH (International Conference on Harmonization) Guidelines Q1A(R2) “Stability testing of new drug substances and products” is the “gold standard” for conducting stability studies. This is valid for “new drug substances or drug products” that are sufficient for a registration application. 5 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

Types of stability:

Types of stability Chemical : Each active ingredient retains its chemical integrity and labeled potency within the specified limit Physical : The original Physical properties including appearance, palatability, uniformity, dissolution and suspendability are retained . Microbiological : Sterility or resistance to microbial growth is retained according to specified requirement . Therapeutic : Therapeutic effect remains unchanged Toxicological : No significant increase in toxicity occurs 6 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

Types of stability study:

Types of stability study Accelerated stability testing Long term testing Stress testing Photo stability study 7 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Continue.. Accelerated stability study : Studies designed to increase the rate of chemical degradation or physical change of an active drug substance or drug product by using exaggerated storage conditions as part of the formal, definitive, storage programme. These data, in addition to long term stability studies, may also be used to assets longer term chemical effects at non-accelerated conditions and to evaluate the impact of short term excursions outside the label storage conditions such as might occur during shipping . Results from accelerated testing studies are not always predictive of physical changes. 8 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Cont.. Long Term (Real Time) Testing Stability evaluation of the physical, chemical, biological and microbiological characteristics of a drug product and a drug substance, covering the expected duration of the shelf life and re-test period, which are claimed in the submission and will appear on the labelling . 9 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Continue… Stress Testing These studies are undertaken to elucidate intrinsic stability characteristics. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated tests. Stress testing is conducted to provide data on forced decomposition products and decomposition mechanisms for the drug substance. The severe conditions that may be encountered during distribution can be covered by stress testing of definitive batches of drug substance. Data from these stress studies could also be useful in understanding the stability profile during manufacturing, storage, shipping, and patient use. These studies provide insight into the potential degradation products and assist in establishing the degradation pathways. These stressed samples could also be used to challenge the stability indicating power of the analytical procedures. 10 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Cont.. Photo stability study The intrinsic photostability characteristics of new drug substances and products should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change. A systematic approach to photostability testing is recommended covering, as appropriate, studies such as: Tests on the drug substance; Tests on the exposed drug product outside of the immediate pack; and if necessary; Tests on the drug product in the immediate pack; and, if necessary Tests on the drug product in the marketing pack. 11 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

What happens due to Instability ? :

What happens due to Instability ? Loss of content uniformity : Suspensions are the drug delivery system most likely to show a loss of content uniformity as a function of time. For such systems, determination of ease of redispersion or sedimentation volume may be included in a stability protocol. Change of microbiological status : The microbiological status of a pharmaceutical product can change significantly with time . First, micro – organisms present in the product at the time of manufacture may reproduce and thus increase the number of viable micro-organisms. Formation of toxic degradation products :- If a drug degrades to a molecular species that is toxic, there must be a special attention given to the quantity of such products. E.g. Conversion of p-amino salicylic acid to p-amino phenol (Toxic). 12 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

Objectives :

Objectives Stability studies provide data to justify the storage condition and shelf-life of the drug product. Requirements of regulatory agencies In many parts of the world, there are legal requirements that certain types of stability tests, as required by regulatory agencies, must be perfomed . Degradation product & possible degradation pathway. Development & validation of stability indicating methodology. To verify that no changes have been introduced in the formulation during manufacturing process that can adversely affect the stability of the product 13 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Cont.. Prevent great loss by recalling the batch due to instability. If any difficulty is found during storage and in marketed product , than industry has to recall all the drugs of that batch which is not economical . But if stability studies are carried out then these problems may be overcome. Providing evidence on how quality of drug substance or product varies with the time under the influence of various environmental factors like temp, humidity and light. Sensitivity to such environmental factors may also dictate the necessity for inclusion of stabilizers in the formulation and will dictate the choice of dosage form and packaging. 14 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


Cont…. To know Loss in concentration of API M odification of any attribute of functional relevance , e.g., a lteration of dissolution time/profile or bioavailability Stability testing also provide idea about selection of proper container e.g. menadione injection is packed in amber colour ampoule to protect from photo degradation. L oss of pharmaceutical elegance and patient acceptability. 15 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.


References Sumie Yoshioka, Valentino J. Stella “Stability of Drugs and Dosage Forms” Kluwer Academic Publishers, 205-25. Kim Huynh- Ba , “Handbook of Stability Testing in Pharmaceutical Development”, Springer,9-42 Ulrich Markens , Pharma Times - Vol 42 - No. 07 - July 2010 ICH harmonised tripartite guideline stability testing of new drug substances and products q1a(r2) current step 4 version dated 6 february 2003 16 /17 Suresh,Soham,Smeet-M-Pharm-1,Dept.of Pharmaceutical technology &Pharmaceutics,LMCP,2011-2012.

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