Drug compound stability testing

Stability testing of drug compound Stability testing of pharmaceutical formulations and packagings... 

Stress testing is an important part of the drug development process as it provides knowledge about the degradation chemistry of drug compounds. This knowledge is used primarily to develop stability-indicating analytical methods but is also useful for other purposes such as formulation develop-... 

Many types of modeling techniques are available in the discovery phase of drug development, from structure activity relationships (SAR) to physiology based pharmacokinetics (PBPK) and pharmacokinetics-/pharmacodynamics (PK/PD) to help choosing some of the lead compounds. Some tests that are carried out by discovery include techniques related to structure determination, metabolism, and permeability NMR, MS/MS, elemental analysis, PAMPA, CACO-2, and in vitro metabolic stability. Although they are important as a part of physicochemical molecular characterization under the biopharmaceutics umbrella, they will not be discussed here. The reader can find relevant information in numerous monographs [9,10]. 

The amount of scientific information contained in a licensing application may be vast (often exceeding 1000 pages). The pharmaceutical company presents evidence to show that every aspect of production of the medicinal product has been controlled and validated and is of an acceptable quality. The application starts with a description of the discovery chemistry for the new drug. This may be a chemical synthesis or an extraction of an active natural product from a plant or microorganism. Spectroscopic (e.g. NMR, MS, IR) and chromatographic (e.g. HPLC, GC) data are presented to show that the correct compound has been synthesised, and that by-products are identified and their levels controlled. The new chemical entity is then subjected to stability testing under accelerated conditions of heat, humidity, etc. to calculate shelf-life and rates of decomposition. Each decomposition product is identified and any potential toxicity is controlled. 

In almost all studies, a reference formulation is needed, either as a comparator for assessment of relative performance compared to the test formulation, or as a simple vehicle, to characterise the drug substance pharmacokinetics. If the aim is to investigate the influence of certain formulations on the rate and extent of absorption, which is the case in early development or IVIVC studies, an oral solution of the drug is the first choice as a reference formulation. Stability of the solution, regarding drug compound degradation and precipitation, is an important factor to verify before study start. Inclusion of a parenteral reference formulation, if feasible, provides additional information, as will be further discussed below. 

Drug substance stability is also addressed in analytical methods development validation studies that require a demonstration of selectivity as part of specificity testing. These results are included in CMC submissions in support of the analytical methods. In this testing, drug substance is commonly stressed with acid, base, oxidation, air, heat, light and other conditions to give rise to products that can be separated from the parent compound. 

Herbal Identity, purity, and stability tests of plant drugs Quantitation of marker compounds... 

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