Non-chromatographic Methods to Support Stability Program

Abstract

Testing of pharmaceutical products is critical in assessing the stability and expected performance of the drug product and API. This chapter will discuss several physical tests as well as those chemical tests that focus on the performance of the drug products. It does not delve into the background theory of the testing but rather gives an overview of the tests and practical information for the analyst performing the tests. Most of these tests are described in detail in the USP. Chapter 9 of this book contains an overview of the USP and its USP-NF requirements for stability purposes.

Physical testing encompasses a wide range of techniques, from visual examination to spectroscopy. It is often the physical attributes which the patient or practitioner can evaluate prior to administration. For example, a particle found in a parenteral formulation can foretell the presence of a new chemical degradant found during stability studies. Many of the procedures in this chapter are performed routinely as part of release or stability testing of API or pharmaceutical products.

Chemical tests such as Karl Fischer testing and pH are also important and conducted routinely.

Analysts in the QC or stability laboratories must be vigilant and attentive to the testing to ensure the products delivered to the public for sale or for a clinical trial meet the design specifications throughout their expiry. All atypical observations must be recorded and elevated to the next level of management for appropriate action. A discussion of investigation is also provided in Chapter 13.

Dissolution testing attempts to characterize a combination of both the physical and chemical nature of the product. The physical aspect of the product may either detract or enhance the dissolution rate; however, so can the chemical nature of the active ingredient. For example, a change in the crystal structure of the API can adversely affect its solubility and hence the dissolution rate.

Due to the rapid advancement of new pharmaceutical delivery systems, this chapter covers only a limited number of techniques. Several of the techniques listed below may be necessary only at time zero or at release rather than being monitored at each stability time point. In addition, this chapter does not cover microbiological tests such as microbial limit, pyrogen, and sterility testing.

Contributions from: Thomas Chambers, Lisa Greve, Tim Navin, Eric Nord, Tore Ramstad, Covance Laboratories