Lipid excipients and delivery systems for pharmaceutical development: a regulatory perspective.

The use of lipid-based dosage forms for enhancement of drug absorption or delivery has drawn considerable interest from pharmaceutical scientists. The unique characteristics of these dosage forms, however, present significant challenges to pharmaceutical industry and regulatory agencies in many ways. For example, safety assessment is necessary when the use of a new lipid excipient is considered. An important question for lipid formulation is whether the drug remains in solubilised form along the gastrointestinal (GI) tract after it is administered. Certain lipid excipients and surfactants have been reported to change intestinal permeability or interfere with enzyme/transporter activity, thereby affecting drug bioavailability. The potential influence of biopharmaceutical and/or pathophysiological factors on the drug or lipid excipient(s) needs to be explored. For a complex lipid-based dosage form, the conventional in vitro dissolution methods may not be appropriate for predicting in vivo performance in view of the convoluted GI processing of the lipid vehicle and formulation Of paramount importance is to identify any gaps in the scientific understanding of lipid-based dosage forms so that regulatory issues can be addressed. More mechanistic studies should be encouraged to facilitate a better understanding of the pharmaceutical characteristics of lipid formulations and complex interactions between lipid excipient, drug and physiological environment. This review discusses some regulatory considerations in the use of lipid excipients and delivery systems for pharmaceutical development. Implications in the regulatory determination of pharmaceutical equivalence, bioequivalence and therapeutic equivalence are also illustrated.