Formulation of piribedil solid lipid particles and their in vitro-in vivo evaluations

SUMMARY In this study, modification of the dissolution rate and thus the enhancement of the bioavailability of a dopaminergic drag, piribedil, which has a low aqueous solubility and short elimination half-life, has been aimed. For this purpose, preparation of micron and submicron particles using solid lipid carriers has been planned. Experimental data obtained from the studies carried on active and adjuvant materials used in formulations were determined to be in accordance with the reference books and company specifications. For the avoidance of solvent residues resulting from the preparation technique, cold and hot homogenization methods have been used to prepare solid lipid particles. Following the obtention of appropriate particle size, piribedil loading and preparation yield by the use of those methods, different formulations have been prepared with various lipid (2.5%, 10%), drug (1%, 5%, 10% of lipid) and surfactant (1%, 1.2%, 2.5%, 5%) concentrations and different surfactant materials (Labrasol®, Tween 80®), to investigate the effects of formulation factors on the particle characteristics. The factors mentioned were found to effect properties of the particles. When the in vitro release from all formulations were examined, pH of the dissolution medium was determined to influence the release of piribedil from particles besides the formulation factors. Piribedil release from all formulations were found to be the fastest in acidic medium. No fit to the mathematical models known could be determined upon investigation of the release kinetics of piribedil from micro- and nanoparticles. Suspensions of intact piribedil and a formulation selected depending on the results obtained from in vitro dissolution and particle size experiments were compared using tremor test in mice. When the same suspension prepared with the same formulation was applied perorally to rabbits, bioavailability was found to be higher than the bioavailability intact of piribedil and that piribedil release was modified. As a conclusion, after in vitro-in vivo evaluation of piribedil solid lipid particles developed for Parkinson's disesase therapy, it has been determined that release rate could be controlled and piribedil bioavailability could be improved. Key words: Microparticle, Nanoparticle, Piribedil, In Vitro-In Vivo Evaluation 11