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A guide for stabilization of pharmaceuticals to oxidation is presented. Literature is presented with an attempt to be a ready source for data and recommendations for formulators. Liquid and solid dosage forms are discussed with options including formulation changes, additives, and packaging documented. In particular, selection of and methods for use of antioxidants are discussed including recommended levels.

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The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.

An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed to determine best fits for chemical stability data, which in turn allows for accurate estimations of shelf life (with appropriate confidence intervals) at any storage condition including inside packaging (based on the moisture vapor transmission rate of the packaging and moisture sorption isotherms of the internal components). These methodologies provide both faster results and far better predictions of chemical stability limited shelf life (expiry) than previously possible. Precise shelf-life estimations are generally determined using a 2-week, product-specific protocol. Once the model for a product is developed, it can play a critical role in providing the product understanding necessary for a quality by design (QbD) filing for product approval and enable rational control strategies to assure product stability. Moreover, this Accelerated Stability Assessment Program (ASAP) enables the coupling of product attributes (e.g., moisture content, packaging options) to allow for flexibility in how control strategies are implemented to provide a balance of cost, speed, and other factors while maintaining adequate stability.

Three nitroxide spin probes (5-, 12-, and 16-doxylstearic acid) were used to investigate the structure of sodium dodecyl sulfate (SDS) micelles and the interfacial layer between water and alumina formed by SDS (hemimicelles of SDS). It was found that whereas the rotational correlation times of the three probes differ in SDS micelles, the effective microviscosities of the probes are the same. In contrast, the microviscosity within the SDS hemimicelles varies according to the distance from the alumina surface: the nitroxide sees a more ordered environment as it is placed closer to the alumina. This represents the first report of variations in flexibility (microviscosity) within a hemimicelle.

This literature review presents hydrolysis of active pharmaceutical ingredients as well as the effects on dosage form stability due to hydrolysis of excipients. Mechanisms and measurement methods are discussed and recommendations for formulation stabilization are listed.