Toward Developing Discriminating Dissolution Methods for Formulations Containing Nanoparticulates in Solution: The Impact of Particle Drift and Drug Activity in Solution.

Enabling formulations are an attractive approach to increase the dissolution rate, solubility, and oral bioavailability of poorly soluble compounds. With the growing prevalence of poorly soluble drug compounds in the pharmaceutical pipeline, supersaturating drug delivery systems (SDDS), a subset of enabling formulations, have grown in popularity due to their properties allowing for drug concentrations greater than the corresponding crystalline solubility. However, the extent of supersaturation generated as the enabling formulation traverses the gastrointestinal (GI) tract is dynamic and poorly understood.

Thermodynamics of aggregate formation between a non-ionic polymer and ionic surfactants: An isothermal titration calorimetric study.

This report examines the energetics of aggregate formation between hydroxypropyl methylcellulose (HPMC) and model ionic surfactants including sodium dodecyl sulfate (SDS) at pharmaceutically relevant concentrations using the isothermal titration calorimetry (ITC) technique and a novel treatment of calorimetric data that accounts for the various species formed. The influence of molecular weight of HPMC, temperature and ionic strength of solution on the aggregate formation process was explored. The interaction between SDS and HPMC was determined to be an endothermic process and initiated at a critical aggregation concentration (CAC).

Development of a Robust Method for Simultaneous Quantification of Polymer (HPMC) and Surfactant (Dodecyl β-D-Maltoside) in Nanosuspensions.

This report describes the development of a chromatographic method for the simultaneous quantification of a polymer, hydroxypropyl methylcellulose (HPMC), and a surfactant, dodecyl β-D-maltoside (DM), that are commonly used in the physical stabilization of pharmaceutical formulations such as nanosuspensions and solid dispersions. These excipients are often challenging to quantify due to the lack of chromophores. A reverse phase size exclusion chromatography (SEC) with evaporative light scattering detector (ELSD) technique was utilized to develop an accurate and robust assay for the simultaneous quantification of HPMC and DM in a nanosuspension formulation.

Mechanistic model and analysis of doxorubicin release from liposomal formulations.

Reliable and predictive models of drug release kinetics in vitro and in vivo are still lacking for liposomal formulations. Developing robust, predictive release models requires systematic, quantitative characterization of these complex drug delivery systems with respect to the physicochemical properties governing the driving force for release. These models must also incorporate changes in release due to the dissolution media and methods employed to monitor release.

Determination of key parameters for a mechanism-based model to predict Doxorubicin release from actively loaded liposomes.

Despite extensive study of liposomal drug formulations, reliable predictive models of release kinetics in vitro and in vivo are still lacking. Progress in the development of robust, predictive release models has been hindered by a lack of systematic, quantitative characterization of these complex drug delivery systems with respect to the myriad of factors that may influence drug release kinetics and the wide range of dissolution media/methods employed to monitor release. In this paper, the key processes and parameters needed to develop a complete mechanism-based model for doxorubicin release from actively loaded liposomal formulations resembling Doxil(®) are determined.