Development of Intramammary Drug Delivery Systems: Novel In Vitro Release Method.

ABSTRACT

The aim of this study was to develop an in vitro release model for intramammary drug delivery system (IMDS) evaluation. This study was the first to establish an in vitro-in vivo correlation with investigation of an IMDS containing lasalocid. Three different methods including the standard United States Pharmacopeia dissolution method with apparatus 2, a modified United States Pharmacopeia method using a dialysis bag, or a specifically designed enhancer cell system, were assessed for the release study. Full cream milk and water were selected as the release media. In vivo evaluation was carried out by administering lasalocid IMDS into the udder of lactating Holstein dairy cows. Milk samples were collected and analyzed at selected time points after treatment. Dissolution data were fitted to various kinetic models. The results indicated that the release rate of lasalocid from IMDS was controlled by factors other than diffusion, which could include the sedimentation of lasalocid to the interface and the wetting of lasalocid particles by water at the interface of oil in the formulation and release media. The results obtained in vivo and in vitro were consistent. The in vitro assessment supports formulation design for early stage development and potentially for in vivo performance analysis.