Key Points of Drug Stability Analysis

rnThe purpose of the stability testing is to investigate how the raw materials or pharmaceutical preparations will change over time under the influence of temperature, humidity, and light, so as to provide a scientific basis for the production, packaging, storage, and transportation conditions of the drug, and to establish the validity period of the drug through the test. In addition to humidity and temperature, other factors may also affect the stability of drugs and active pharmaceutical ingredients (APIs), such as pH, excipients, API content concentration and retention time. These factors should be included in the overall stability assessment and drug development process. Stages of stability researchrnStability testing includes influencing factor testing, accelerated testing and long-term testing. The influencing factor testing is carried out with a batch of APIs or a batch of preparations. Accelerated testing and long-term testing require three batches of test products. Generally, stability testing should start from early drug development, early formulation development. Usually, the accelerated stability test is performed first, followed by the confirmatory long-term stability test, which is considered to be the best stability research practice. It should be noted that accelerated stability testing can represent long-term testing and will not cause degradation pathways that are not present in the nominal storage environment. Once the long-term stability data is obtained, the accelerated stability estimate can be calibrated and corrected. Two stability research methodsrnIf the parameters indicate that stability changes with time, regression analysis is the main method to determine stability, because time is the main factor affecting stability. The following two methods are based on the degradation rate and the influencing factors related to the degradation rate. When the sample size is small, the degradation rate is most suitable for early development; when the sample size and time interval contain more data, the corresponding time of the impact factors related to the degradation rate is most suitable for long-term research. Generally, the use of nonlinear and other types of special linear models (such as sqrt, 1/x, logarithm, exponential, polynomial) should be avoided as they may produce meaningless and unreproducible drug expiration estimates. Measures to improve drug stabilityrnBased on the above analysis, the following measures can be considered to improve drug stability: Choose the right excipientsrnExcipients have a greater impact on the stability of the drug, mainly including pH, particle size, viscosity, type, etc. It needs to be comprehensively evaluated through the compatibility of raw and auxiliary materials, acceleration, long-term stability test and the smoothness of the process. Choose the right packaging materialrnFor light-sensitive drugs, for example, researchers can choose double aluminum, brown packaging, and aluminum tube to shade and avoid light. For drugs that are sensitive to humidity, packaging materials with better moisture resistance should be considered. These packaging material selection experiments should be systematically designed and researched in the early stages of development to obtain more adequate data support and reduce stability risks. Increase antioxidants and nitrogen fillingrnAdding antioxidants (such as sulfite or PG, BHA and other radical blockers, VC that enhances the antioxidant effect) in the prescription can prevent the degradation of the raw material or the main drug in the preparation, and nitrogen can also prevent the degradation of the raw materials. Reduce the introduction of metal ionsrnMetal ions such as copper and iron come from excipients, coating powder, water, equipment, etc., and sometimes have a certain impact on the stability of the drug, therefore, sometimes it is necessary to consider adding metal-chelating agents, such as tartaric acid and citric acid. Conclusion Stability analysis is the basis for all drug development and manufacturing. All organizations need to have a clear vision for the appropriate stage of stability research design so as to make sure that stable products can meet all regulatory requirements before entering markets.