Drug stability testing/studies of a pharmaceutical product may be defined as the capability of a formulation to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications at a defined storage condition.
Any Pharmaceutical products are expected to meet their specifications for identity, purity, quality, and strength throughout their defined storage period at specific storage conditions, in a specific container/closure system.
Stability Testing of Pharmaceutical Products
The stability of a pharmaceutical product may be defined as the capability of a formulation to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications at a defined storage condition.
Stability testing is to be performed to provide evidence on how the quality of a drug substance or formulation varies with time under the influence of various environmental factors such as temperature, humidity and light, and to establish shelf life for the formulation and recommended storage conditions.
Stability studies should include testing of those attributes of the drug substance that are susceptible to change during storage and are likely to influence quality, safety, and/or efficacy. In case of formulations the testing should cover, as appropriate, the physical, chemical, biological, and microbiological attributes, preservative content (e.g., antioxidant, antimicrobial preservative), and functionality tests (e.g., for a dose delivery system).
In general, a drug substance should be evaluated under storage conditions that test its thermal stability and, if applicable, its sensitivity to moisture.
The stability of a commercial pharmaceutical product is expressed as an expiration date (expiry).
Expiry Date or shelf life of a drug product
The time in which a drug product will remain stable when stored under recommended conditions in a specific packaging/closure system.
Note: An expiry date, which is expressed traditionally in terms of month and year, denotes the last day of the month.
Note: If a dry product is to be reconstituted at the time of dispensing, expiration dates are assigned to both the dry mixture and the reconstituted product.
Manufacturing Date:
The date of manufacture is defined as the date in which the active pharmaceutical ingredient is first combined with a drug product excipient.
The stability of a pharmaceutical product is investigated throughout the various stages of the development process like Pre-formulation & further continues during the formulation development stages.
The stability typically must also assess the robustness of the drug product through its supply chain. It is not unusual for temperature excursions to occur during these transfers of control.
The use of kinetic and predictive studies for establishing expiration date for pharmaceutical products is now accepted worldwide. Minimum acceptable potency level over the shelf life of a drug product is 90% of labelled potency (accepted worldwide).
The necessity of stability studies
- Product instability/chemical degradation on storage lead to lowering the concentration of the drug in the dosage form. Ex. Digoxin, theophylline
- During decomposition of active drugs may produce toxic products. Ex. PAS P-Aminophenol (toxic); Degraded penicillin- G infusion may cause Allergy
- Instability may be physical – mottling of tab creaming, sedimentation, caking etc.
Arrhenius Equation (Influence of Temperature on Drug Product)
Arrhenius Eq = special rate of reaction at 2 or 3 time with every 10 degree centigrade rise in temperature
K = Ae-Ea/RT
K = specific rate constant
A= Arrhenion factor
Ea = activate E
R = ideal gas constant (1.987 Cal/ mol. dg)
T = Ab. temp.
Additional overages in Pharmaceutical Product
- These are added to Multivitamin preparation
- An excess amount of drug is added to formulation/ preparation to maintain 100% of the labeled amount during the excepted shelf life period (Schedule –P of D & C Act)
- Average is calculated from accelerated stability studies.
- During shelf life = 10% composition is permitted.
- When overage is added- the product must retain 100% labeled drug during the shelf life.
Drug Stability Testing/studies of new drug substances and formulations
As Drug And Cosmetic Act 1940 & Rules 1945:
Long-term stability testing:
Long-term testing should cover a minimum of 12 months‘ duration on at least three primary batches of the drug substance or the formulation at the time of submission and should be continued for a period of time sufficient to cover the proposed shelf life.
Accelerated Stability testing
Accelerated testing should cover a minimum of 6 months duration at the time of submission.
The stability studies for drug substances should be conducted either in the same container – closure system as proposed for storage and distribution or in a container – closure system that simulates the proposed final packaging. In case of formulations, the stability studies should be conducted in the final container – closure system proposed for marketing.
| S. No. | Storage condition for product | Type of Study | Duration of study | Study conditions |
|---|---|---|---|---|
| 1. | Substances and formulations intended to be stored under general conditions | Long term | 12 months | 30°C ± 2°C/65% RH ± 5% RH |
| Accelerated | 6 months | 40°C ± 2°C/75% RH ± 5% RH | ||
| 2. | Drug substances and formulations intended to be stored in a refrigerator | Long term | 12 months | 5°C ± 3°C |
| Accelerated | 6 months | 25°C ± 2°C/60% RH ± 5% RH | ||
| 3. | Drug substances and formulations intended to be stored in a freezer | Long term | 12 months | – 20°C ± 5°C |
| 4. | Drug substances intended for storage below –20°C (minus 20°C) | shall be treated on a case-by-case basis | – | – |
