Pharmaceutical Stability Test

2021-07-23

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The stability of a drug substance or preparation refers to its ability to maintain physical, chemical, biological and microbiological properties. Stability research is based on the systematic research and understanding of APIs or preparations and their production processes. The quality characteristics of APIs or preparations obtained through design tests will vary under the influence of various environmental factors (such as temperature, humidity, light exposure, etc.). The laws of time change, and based on this, provide supporting information for the determination of the prescription, technology, packaging, storage conditions, transportation, use, and expiration date/re-inspection date of drugs Drug stability research is a process of comprehensive quality assessment of drugs using scientific analysis methods and principles, and plays an important role in the entire life cycle of drugs.

The stability of a drug substance or preparation refers to its ability to maintain physical, chemical, biological and microbiological properties. Stability research is based on the systematic research and understanding of APIs or preparations and their production processes. The quality characteristics of APIs or preparations obtained through design tests will vary under the influence of various environmental factors (such as temperature, humidity, light exposure, etc.). The laws of time change, and based on this, provide supporting information for the determination of the prescription, technology, packaging, storage conditions, transportation, use, and expiration date/re-inspection date of drugs Drug stability research is a process of comprehensive quality assessment of drugs using scientific analysis methods and principles, and plays an important role in the entire life cycle of drugs.

This article analyzes the types of instability in drug stability research, factors affecting stability, design ideas for stability experiments, measures to improve stability, and problems in stability investigations.

A type of drug instability

It is found from the stability investigation test that the types of drug instability can basically be divided into three categories, namely, physical instability, chemical instability, and biological instability.

Physical instability

Physical instability is mainly due to changes in properties caused by conditions such as time, temperature and humidity, such as black spots, softening, brittleness, layering of emulsions on the surface of tablets, and agglomeration of granules.

Chemical instability

Chemical instability refers to the instability of the drug due to chemical reactions (such as hydrolysis, oxidation, etc.), such as increased moisture, light, oxygen, compatibility of raw materials and excipients, compatibility of drugs and packaging containers during the inspection process. Degradation of the drug caused by the increase of impurities, decrease in content and so on. In addition, the crystal form change that may be caused by the above-mentioned reasons during the production process is also an important factor. Related testing indicators such as related substances, isomers, solution clarity and color, polymer, content, crystal form, etc.

Biological instability

Biological instability is mainly due to instability caused by microbial contamination and other factors, which can cause deterioration and corruption of medicines. The relevant test indicators in the drug application, such as tablets, need to be investigated for microbial limits at least at the initial and end time points of the stability investigation.

Two factors affecting stability

The chemical structure of the drug itself

The structure of a drug is the most important in stability. Some drug structures contain groups that are prone to degradation, such as ester bonds, conjugated double bonds, thioether bonds, etc. Sometimes they will be degraded by hydrolysis, light, and oxidation, resulting in impurities . Methods to change the properties of solid drugs and improve their stability include increasing the melting point, selecting non-hygroscopic crystal forms (crystals or salt formation), and changing the external morphology.

Excipient factors

The chemical structure, impurities, physical state, water content, particle size, surface area, particle morphology, ratio of the main drug and the auxiliary material of the excipients can all have an impact on the stability. The research on the compatibility of raw and auxiliary materials is becoming more and more important, because it can provide reference for the selection of auxiliary material types, models, particle sizes, etc. or for the selection of processes in the early stage of research and development, such as the choice of dry process or wet process.