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Accelerated Stability Testing in Expiration Dating of Pharmaceutical Dosage Forms

When pharmaceuticals are subjected to expedited stability testing, the medications produced in the factories are found to be stable in shelf life.
When pharmaceuticals are subjected to expedited stability testing, the medications produced in the factories are found to be stable in terms of shelf life. At a certain period, the drug particles begin to degrade and lose their stability. For this reason, the finished pharmaceutical drugs must contain an expiration date on the drug product. In the finished pharmaceutical product, test stability is also an essential point to follow. It measures the appropriateness and accuracy of the expiration date of the drug.

Every drug particle is different as it shows a huge difference in the physio-chemical properties of the excipients, drug manufacturing process, drug formulation, containers and closures, proposed storage conditions, and the drug stability to maintain the quality as well as purity. The quality and stability of pharmaceutical products are increased by preservatives and antioxidants. Due to the differences in drug particles, it is impossible to apply a certain set of rules for each product in all situations. For the finished product, Current Good Manufacturing Practice (cGMP) has brought requirements concerning the expiration date of the manufactured products

Expiration Dating

Absence of an Expiration Date
The lack of an expiry date on items manufactured after September 29, 1979 is intended to trigger regulatory action. It does not apply to the medications listed in 211.137 (e), (f), and (g).

As per the exemption of 211.137, Over-the-counter (OTC) is utilized in acceleration testing practice. These are the drugs that remain stable for 3 years. According to the study, over-the-counter medications like paracetamol are safe, but excessive usage can lead to Hepatic Necrosis.

Products Intended for Reconstitution
The drugs are meant for reconstitution or do not have expiration data for the reconstituted product. After that, another expiration date will be renewed for the particular product after reconstitution. The fact is termed as out of compliance with 211.137 (c). There are also few studies on the expiration date of drugs.

Stability Testing

Stability tests provide evidence of the degree to which the performance of a substance or product fluctuates over a certain time and in the context of environmental conditions, such the temperature, humidity, and light.

The research investigations look at characteristics that can vary over time and have an impact on the product's quality, safety, and efficacy.

Testing typically covers the microbiological, chemical, and physical aspects:
  • Physical Surface: Appearance, melting point, and water content.
  • Chemical Assay and degradation products, associated chemicals and solvents that remain
  • Microorganisms: Growth in microorganisms as well as the efficiency of preservatives, like Antimicrobials, antioxidants as well as antimicrobials.
The frequency of testing points for long-term studies must be enough to determine the stability profile of extended duration.

For drugs with the potential for re-testing that is at least 12 months the testing frequency in a long-term storage environment is typically every three months for the first year, every six months during the second year, and then annually throughout the time of the proposed re-test.

The recommended testing interval for the intermediate storage is at least four times, which includes the final and initial time points, in an entire 12-month study.

For storage conditions with accelerated speed, the test frequency should be set to be at least three times, which includes the first and last times for a 6-month study. A substance that is a drug must be tested under conditions of storage that test its thermal stability as well as its susceptibility to humidity.

Written Stability Testing Program
The stability test of a pharmaceutical product is mainly done for storage condition and expiration date. For the stability testing of Active Pharmaceutical ingredients (API), drugs in processing, as well as marketed pharmaceutical products WHO and ICH have introduced several guidelines. The main aim of the stability test is to undergo a re-test. Not only that, it defines storage conditions as well that could influence the quality of the pharmaceutical product. Furthermore, it is influenced by elements such as temperature, humidity, and light. That’s why it is required to undergo a written stability testing program.

Supportive Stability Data

Number and Size of Batches
Accelerated testing is done in smaller batches than normal production. For the long-term ability program, three initial batches are minimal to establish an expiration date. Stability testing of the drudrugsis not only limited to certain production batches. In this instance, a percentage of each year's manufacturing batches is subjected to a continuous stability programme. The complex unit is dosage form. In the production process, there are certain continued variables such as suppliers, raw materials, and equipment.

Accelerated Studies
Accelerated life testing ipracticeactise of submitting a product to conditions (stress, strain, temperatures, voltage, vibration rate, pressure, and so on) that are outside of its usual service parameter to find flaws and potential modes of failure in a short amount of time.

Engineers can forecast a product's service life and maintenance intervals by examining the product's response to such testing.

Test Intervals
The interval test is one variation of the gap test. The main concept is to look at the time intervals between occurrences of the same value.

Consider the case where random returns the value 3.

Up to and including the next occurrence of 3, count the number of values generated by random.

Rep this process for each time the value 3 appears in the output sequence.

Count the number of 1, 2, 3, and so on length separations.

Calculate a chi-square statistic for each separation length using these counts and the expected counts, and compare the result to the critical value of a chi-square random variable with the proper number of degrees of freedom and a probability of 0.95.

When a tentative expiration dating term of more than three years is established purely based on accelerated testing data, it is discouraged. In the article, we are introduced to different types of tests that are used to determine the stability of a pharmaceutical product.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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