STABILITY TESTING DURING PRODUCT DEVELOPMENT

 

STABILITY TESTING DURING PRODUCT DEVELOPMENT

In order to include quality, efficacy, and safety into a medicine formulation, stability testing of pharmaceutical goods is a complicated collection of processes requiring significant expense, time consumption, and scientific skill.

Understanding the drug development process and the numerous activities and milestones that are essential to a thorough development plan is the only way to guarantee the scientific and financial success of a pharmaceutical product.

The pharmaceutical analysis and stability tests that are necessary to ascertain and ensure the identity, potency, and purity of ingredients as well as those of the formed products are among the most crucial tasks during the developmental stages.

A pharmaceutical product's capacity to maintain its physical, chemical, microbiological, toxicological, protective, and informational requirements in a certain container or closure system is known as stability.

In other words, it refers to how much of a product's original traits and attributes it retains during the course of storage and use, as long as those boundaries are observed.

Hence, stability testing assesses the impact of environmental factors on the quality of a therapeutic ingredient or a formed product, which is used to forecast its shelf life, identify the best conditions for storage, and recommend labelling guidelines.

Also, the results of the stability testing are a crucial prerequisite for regulatory approval of any medicine or formulation.

A multitude of elements that affect a pharmaceutical product's stability are involved in stability testing, which is why it is regarded as a difficult process.

The stability of the active ingredient(s), interactions between the active ingredient and excipients, manufacturing procedures used, dosage form type, packaging container/closure system, and environmental conditions for light, heat, and moisture encountered during transportation, storage, and handling are some of these factors.

The stability of a pharmaceutical product can also be greatly affected by degradation reactions like oxidation, reduction, hydrolysis, or racemization. These reactions are also influenced by environmental factors like reactant concentration, pH, radiation, catalysts, and time between production and use of the product.

A pharmaceutical product's stability may be impacted by alterations in its appearance, consistency, content uniformity, clarity (solution), moisture content, particle size and shape, pH, and package integrity.

These physical alterations may result from impact, vibration, abrasion, and temperature changes like freezing, thawing, or shearing, among other things.

The formation of degradation products, loss of active pharmaceutical ingredient (API) potency, and loss of excipient activity, such as antimicrobial preservative action and antioxidants, among other things, may result from chemical reactions in pharmaceutical products like solvolysis, oxidation, reduction, racemization, etc.

Microbiological modifications, such as the expansion of bacteria in non-sterile products and modifications in preservative efficacy, can also have an impact on a pharmaceutical product's stability.

STABILITY TESTING METHODS

During various stages of the product development process, stability testing is a standard technique carried out on medicinal ingredients and products.

Accelerated stability testing (at relatively high temperatures and/or humidity) is used in the first phases to identify the kinds of degradation products that could be discovered during long-term storage.

The shelf life and expiration dates of a product are determined through testing under less rigorous conditions, i.e. those suggested for long-term shelf storage, at slightly increased temperatures.

Pharmaceutical stability testing's main goal is to give consumers a reasonable level of assurance that the products will maintain an acceptable level of quality and fitness for use throughout the time they are on the market and available to patients, and will remain safe for consumption up until the patient consumes the last unit of the product.

The following four types of stability testing techniques have been identified based on the objectives and steps taken.

1.   Real-Time stability testing

2.   Accelerated stability testing

3.   Retained sample stability testing

4.   Cyclic temperature stress testing

       Real-Time stability testing

The test period for real-time stability testing is often longer in order to allow for significant product degradation under advised storage settings.

 The test's duration is determined by the product's stability, which should be lengthy enough to clearly show that no detectable deterioration exists. It must also enable one to differentiate between deterioration and inter-assay variance.

The stability of the reference material also refers to the reagents' stability and the consistency of the instrument's performance over the course of the stability testing.

 Accelerated stability testing

In accelerated stability testing, a product is subjected to stress at a number of high temperatures in order to determine the amount of heat input necessary to result in product failure.

This is done to put the product in a situation where its degradation is accelerated.

The expected shelf life or the relative stability of several formulations are then determined using this information.

This typically gives a head start on estimating the product shelf life, cutting down on the time needed for development.

Stress factors that are applied during accelerated stability testing in addition to temperature include moisture, light, agitation, gravity, pH, and packaging.

In an accelerated stability test, the materials are stressed, cooled after straining, and then simultaneously analyzed.

In comparison to real-time stability testing, the likelihood of measuring system instability is lower due to the short analysis length.

GUIDELINES FOR STABILITY TESTING

ICH Code	Guideline title
Q1A	Stability testing of New Drug Substances and Products (Second Revision)
Q1B	Stability testing Photostability testing of New Drug Substances and Products
Q1C	Stability testing of New Dosage Forms
Q1D	Bracketing and Matrixing Designs for stability testing of Drug Substances and Products
Q1E	Evaluation of stability data
Q1F	Stability data package for Registration Applications in Climatic Zones III and IV
Q5C	Stability testing of Biotechnological/Biological Products

   

PROTOCOL FOR STABILITY TESTING

The stability testing protocol is a requirement before stability testing can begin and is unavoidably a written document that outlines the essential elements of a regulated and well-controlled stability study.

The testing conditions depend on the kind of dosage form, the proposed container-closure system, and the inherent stability of the molecule, so the protocol varies on the kind of drug substance or product.

Whether the drug is brand-new or has been on the market for some time can also affect the protocol.

The following details should be included in a stability protocol that is carefully thought out.

1.   Batches

2.   Containers and closures

3.   Orientation of storage of containers

4.   Sampling time points

5.   Sampling plan

6.   Test storage conditions

7.   Test parameters

8.   Test methodology

STABILITY TEST EQUIPMENT

Stability chamber is the name of the apparatus used for stability testing. 

They are specialized environmental chambers that allow the evaluation of product stability based on real-time, expedited, and long-term protocols while simulating the storage situation.

They come in reach-in and walk-in variations.

While walk-in chambers are preferable for long-term testing, smaller chambers are preferred for rapid testing because the retention period of items is substantially lower in these cabinets.

Such chambers or rooms are designed and qualified to guarantee that each sample in the chamber has an equal exposure to the given circumstances.

Because these chambers must be used continuously for years, reliability and toughness are expected.

They are equipped with the proper recording, security, and alarm systems.

Moreover, photostability chambers are offered and used both with and without controlling the temperature and humidity.

In photostability chambers, two different types of light sources are typically used: one is a combination of cool white and near UV fluorescent tubes, and the other is an artificial daylight lamp, such as a xenon or metal halide.

To achieve a total exposure of 1.2 million lux hours, it is necessary.

   With a lux metro, the intensity of visible light is calculated.

The number of exposure hours required is calculated.