The use of polymorphic state modifiers in solid lipid microparticles: the role of structural modifications on drug release performance

This study investigates the correlation between the structural and release properties of solid lipid microparticles (MPs) of tristearin containing 5% w/w of four different liquid additives used as crystal modifiers: isopropyl myristate (IM), ethyl oleate (EO), oleic acid (OA) and medium chain triglycerides (MCT). All additives accelerated the conversion of the unstable α-form of tristearin, formed after the MPs manufacturing, to the stable β-polymorph and the transformation was completed within 24 h (for IM and EO) or 48 h (for OA and MCT). The kinetic of polymorphic transition at 25°C was investigated by simultaneous synchrotron SAXS/WAXS and DSC analysis after melting and subsequent cooling of the lipid mixture. After crystallization in the α-phase, additives accelerate the solid-solid phase transformation to β-tristearin. SAXS data showed that two types of structural modifications occurred on MPs during storage: compaction of the crystal packing (slight decrease in lamellar thickness) and crystal growth (increased number of stacked lipid lamellae). The release behaviour of a model hydrophilic drug (caffeine) at two different amounts (15% and 30%) from MPs was studied in water and biorelevant media simulated the gastric and intestinal environment. It was particularly significant that the introduction of IM, EO and MCT were able to prolong the drug release in water, passing from a diffusion-based Higuchi kinetics to a perfect zero-order kinetic. Moreover, the overall re...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Source Type: research