Drug stability defined

The effect of complex formation on drug stability can often be described in terms of the processes represented by Scheme 76. If drug D forms a complex with ligand L, the complex (assuming a 1 1 interaction) can be defined by a complexation constant K ... 

Excipients contained in the original dosage form also have to be taken into account and can decrease the product s appearance (insolubles) or even reduce the drug stability. The end-product is therefore a complex and not well-defined admixture of numerous components. Ideally, it should be prepared with the pure active pharmaceutical ingredient when possible. 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

A stability-indicating method is a validated quantitative analytical procedure that can detect the changes with time in the pertinent properties of the drug substance and drug product under defined storage condition. A stability-indicating assay method accurately measures the active ingredient(s) without interference from other peaks and is sensitive... 

The solid matrix of SLN protects the drug from hydrolysis and oxidation. Chemical stability of tocopherol and retinol improves considerably [17,39], with tocopherol improving by 57% compared with an aqueous dispersion. The degree of retinol stabilization depends on the nature of lipid and surfactant [39]. For each drug, the optimal preparation has to be defined individually. 

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