Influence of High-Pressure Compaction of Binary Mixtures on Solubility, Dissolution and Wettability of Borderline Poorly Soluble Drugs Employing Standard Excipients

Abstract

Many of new drug candidates are impaired by low aqueous solubility and slow dissolution rates, which may hinder their pharmacological response. Therefore, there is an increasing need to investigate and implement new approaches that are simply applicable in the formulation development to enhance solubility and/or dissolution kinetics of sparingly soluble drugs. <br /> The primary aim of this research was to develop new carrier systems (enabling formulations) for an optimized administration of particularly borderline poorly soluble drugs. The proposed strategy involves the preparation of solid compacts of binary mixtures consisting of a crystalline drug and a hydrophilic excipient that has polar functional groups, by compaction under high-pressure. The potential of the strategy on solubility, dissolution and wettability was evaluated. <br /> Intrinsic dissolution rate test was applied as a key parameter to characterize all drug compacts and to assess the influence of the proposed approach on dissolution process. <br /> The potential impacts and outcomes, induced by the application of proposed strategy on the physicochemical properties of drug within the formulated product, were investigated. This included the ability to induce a crystal modification regarding the neat drug solid-state attributes, to produce higher drug/excipient interactions and/or to manipulate the overall solid surface and its wettability. The influence of neat excipients properties on the compacted systems was also investigated. Subsequently, the experimentally investigated impacts were correlated with the obtained Intrinsic dissolution rates for the involved formulations.