ABSTRACT:
Objective: Tyrosine kinase inhibitor, Lapatinib (LAP) is highly lipophilic in nature and presents challenges with regard to its low and variable oral bioavailability. Polymer-based solid dispersion technology has been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. In the present research work, approaches were taken to improve the dissolution characteristics of LAP by developing suitable systems of solid dispersion. Methods: Solid dispersions of lapatinib were prepared utilizing techniques like solvent controlled coprecipitation, fusion, nanoprecipitation and spray drying. Polymers with different ionic characteristics like Eudragit® EPO (cationic), Eudragit® L 100 55 (anionic), HPMCP HP 55 (anionic), HPMC AS (anionic) and Povidone K 30 (non-ionic) were employed at three different ratios of 1:1, 1:2 and 1:3 to prepare the solid dispersions of weakly basic lapatinib. Dissolution study in media corresponding to different physiologically relevant pH was performed to understand the effectiveness of the technique and effect of the polymer. Additionally, samples were also subjected for X-ray powder diffraction study to understand the nature of the drug in the solid dispersion systems. Results: It was observed that irrespective of the pH of the dissolution media, the dissolution rate of solid dispersions of LAP prepared with anionic polymers in particular HPMCP HP 55 is more which is attributed to the weakly basic nature of lapatinib. The diffractograms show substantial decrease in the crystallinity of lapatinib in the solid dispersions. Conclusion: The combination of solid dispersion technique with supersaturable systems appears to hold promise for improving dissolution and bioavailability of poorly soluble drugs. Solid dispersions significantly increase dissolution of LAP, which can be a starting point of a new LAP formulation with improved bioavailability. The selection of polymers that can inhibit crystallization of LAP in a supersaturated state becomes the key factor for an effective formulation. The present work is an attempt in this direction.