Design and Study of Drug Delivery of Poorly Water Soluble Drugs With Improved Pharmacokinetics

Abstract

Solubility enhancement continues to remain a major challenge in the pharmaceutical industry. There is a lot of work published showcasing different approaches, challenges, and the benefits observed by using those processes and excipients. The present work was targeted to target the use of an Industry feasible, acceptable, and scalable process. The work was aimed to test a novel carrier, which could address certain challenges seen with currently available carriers. The aim was also to derive an understanding of the process of solid dispersion preparation would have any impact on in-vivo performance. The authors also tried to show the solubility enhancement range for actives with aqueous solubility from 10 ng/mL to 10 μg/mL. In the present research work, the authors identified a methacrylic polymer, which is used for moisture protection and taste masking for solubility enhancement. No reports were shown for use of Kollicoat Smarseal in preparation of solid dispersion. Kollicoat Smartseal 30 D was spray dried to prepare the solid powder of Kollicoat Smartseal. The FTIR image of spray-dried Kollicoat Smartseal polymer with that of reference IR graphs & values indicated that the polymer did not undergo any chemical medication. The studies with this polymer concluded that the carrier did not decompose up to 220°C. Thus, during solid dispersion preparation through melt extrusion and spray drying temperatures as high as 220°C can be exposed to the polymer. Different toxicity data available from the supplier (BASF) shows that the polymer has very good oral safety up to 5000 mg/Kg/day. Thus, high polymer concentration can be used for the preparation of solid dispersion. The low glass transition temperature of the polymer allowed processing at a low temperature of 95°C. Studies carried out with Itraconazole and Simvastatin show that Kollicoat Smartseal can form Solid Dispersion through Melt Extrusion and Spray Drying. The solid dispersion formulated with Kollicoat Smartseal can improve solubility for Simvastatin and Itraconazole when used through two solid dispersion techniques. Solubility enhancement is better compared to Copovidone, which is the most preferred carrier. At the same time processing was much better than Copovidone. Even though Kollicoat Smartseal exhibits pH dependant solubility the solid dispersion formulated with this carrier exhibited solubility enhancement over a wide range of pH. Formulations such as tablets were successfully formulated with Kollicoat Smartseal prepared solid dispersion. A faster Dissolution rate was seen as against the marketed formulation. The stability studies carried out at acceleratedstudies have shown good stability and solubility. The results were not limited to in-vitro performance, but In vivo results exhibited higher bioavailability than the plain active. Similar Bioavailability performance was independent of the process of preparation of solid dispersion for Itraconazole. The in vivo results showed higher bioavailability than the standard carrier like copovidone for both the process of solid dispersion for Itraconazole. Thus, it was concluded that Kollicoat Smartseal is a NOVEL and SAFE polymer for the preparation of Solid Dispersion through Solid Dispersion and Melt Extrusion for a wide array of actives. The investigated carrier is useful to improve the solubility of similar BCS class-II drugs.