Study of the drug release profile of novel polymer-drug matrix formulations prepared by hot melt extrusion /

Abstract

Hot Melt Extrusion (HME) is an emerging technology in the pharmaceutical industry for manufacturing drug delivery devices. In the HME process, the polymer and drug are melted and mixed with the help of heat and mechanical stresses. HME offers various advantages compared to other pharmaceutical processes; it is a solvent-free process, it is possible to manufacture different dosage forms including implants, tablets, granules, pellets, it can enhance the solubility and bioavailability of poorly water-soluble drugs, and it is a continuous process. However, due to the involvement of heat and shear stresses, the processing of heat-sensitive polymers, e.g. PLA, with drugs is challenging. Polylactide (PLA) is a bioresorbable FDA approved biopolymer. In recent years PLA has gained particular interest in the medical industry, and PLA-based drug-eluting implants are used in many different applications, including dental, cardiac, orthopaedic and tissue engineering applications. The benefit of using PLA-based drug-eluting implants is that they slowly release the entrapped drug and degrade naturally into non-toxic by-products over time, excluding the need for any surgical method for their removal. However, despite the advantages of HME processing, achieving consistent quality products can be challenging. One of the challenges faced by the pharmaceutical industry is that large ratios of new drug entities belong to class BCS II, which are poorly water-soluble drugs. Poor solubility of drugs has been a major hindrance to the development of more effective drug delivery methods. Soluplus (polyvinyl-caprolactam polyvinyl-acetate copolymer polyethylene glycol graft) is an amphiphilic polymer and has the ability to solubilise the poorly water soluble drugs and has been developed to enhance the bioavailability of poorly water-soluble drugs. In this work, we explore the production of drug-loaded PLA and Soluplus products with a HME process. Two different drugs, including ibuprofen and dexamethasone, are extruded with PLA. Further, ibuprofen which is a poorly water-soluble drug (melting point 77°C) is extruded with Soluplus. The purpose is to investigate the processability as well as the effect of drug loadings and processing conditions, including temperature and screw speed, on the drug release profile. DSC is used to study the miscibility of the polymer-drug matrix, FTIR is used to study the interaction of polymer-drug matrix, and drug-dissolution tester is used to study the percentage drug release