In vitro release kinetic pattern of indomethacin from poly(D,L-lactide) nanocapsules

Indomethacin nanocapsules were prepared by interfacial deposition of poly(D,L-lactide) polymer following displacement of acetone from a lipophilic phase to an aqueous phase. Highly solvated bilayers of phospholipids in excess in the formulation were formed and easily detected by TEM. In vitro release kinetic analysis of indomethacin from pure nanocapsules prepared with poloxamer as sole emulsifier, mixed colloidal suspension (nanocapsules and liposomal vesicules), and multiamellar phospholipidic bilayers revealed that drug release in phosphate buffer sink solution was drastically delayed and incomplete as a result of the high indomethacin solubility in the oily core, poloxamer micelles, and phospholipidic bilayers, respectively. The release process was thus dependent on drug partition from the colloidal suspension phases to the external sink solution. However, addition of albumin to the sink solution markedly enhanced the indomethacin release due to protein binding affinity. A kinetic model equation dealing with biphasic systems in which a drug is dissolved or partitioned between the lipophilic and hydrophilic phases of a dispersed system is proposed and found suitable for the description of indomethacin release from the mixed colloidal suspension only.