Assessment of Drug Release from Oil Depot Formulations Using an In Vitro Model—Potential Applicability in Accelerated Release Testing

Abstract

In vitro drug release and transport rates from oil depot formulations under nonsink conditions have been investigated in the rotating dialysis cell model. Eight model drug compounds and eight oil vehicle compositions were used for the releaseexperiments. The experimentally obtained apparent first-order rate constants related to the drug appearance in the acceptor phase after initial instillation of a drug-containing oil solution were found to be in excellent agreement with the rate constants obtained from a theoretically derived expression. It was observed that the drug oil-water distribution coefficient was the key parameter influencing the release characteristics. As compared with ketoprofen, flurbiprofen exhibited a higher affinity for the oil, resulting in a significantly lower and more slowly decreasing drug concentrations in the aqueous donor compartment. Release profiles for prilocaine and the more lipophilic agent bupivacaine after incorporation of both drugs in fractionated coconut oil were characterized by a fast release of prilocaine, whereas bupivacaine was liberated much slower to the acceptor phase. The high oil-buffer interfacial area generated in vitro by rotation of the donor cell tends to overestimate release rates in comparison to those expected in vivo, for example, after intra-articular administration of oil solutions. The present in vitro method may constitute a valuable tool in accelerated in vitro release testing of parenteral oil depot formulations in areas comprising formulation design and product quality control.

Keywords:

• oil solution
• depot formulation
• intra-articular drug delivery
• rotating dialysis cell
• in vitro release testing