Packaged product, stability prediction

Methods for Prediction of Effects of Packaging on Stability of Drug Products... 

Final packaged product must be shown to be stable up to at least the expiry date. These stability data are obtained by actual testing through the expiry date and beyond. Early term stability data may be submitted to FDA or other regulatory bodies to support preliminary expiry dating. These data as well as data obtained under accelerated storage conditions may be utilized to predict ultimate stability and to establish rates and kinetics of degradation. 

A preformulation package provides essential information on the physicochemical properties of the drug, such as pKa, aqueous solubility, aqueous stability, light stability, and lipophilicity (this may predict potential for binding to plastic/rubber pump components). The pK s of any ionisable groups are particularly important as they affect stability, solubility and lipophilicity and should indicate the optimum pH for the nasal solution. For physiological reasons, formulated products are usually in the range of pH 4.0-7.4. 

Accelerated stability tests provide a means of comparing alternative formulations, packaging materials, and/or manufacturing processes in short-term experiments. As soon as the final formulation and manufacturing process have been established, the manufacturer carries out a series of accelerated stability tests which will enable the stability of the drug product to be predicted and its shelf-life and storage conditions determined. Real-time studies must be started at the same time for confirmation purposes. Suitable measures should be taken to establish the utilization period for preparations in muitidose containers, especially for topical use. 

The formulation has to meet the needs of the patient with active substances, excipients, dosage form and package, it has to meet (regulatory or professionally set) product specifications and it should support a sound production process (see Chap. 17 Product design). The preparation s stability plays a large role, its shelf life has to be predicted and analysed (see Chap. 22 Stability) and instructions for use have to be developed (see Chap. 37 Instructions for use). 

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