The development of PVP-based solid dispersions using hot melt extrusion for the preparation of immediate release formulations

Bioavailability and clinical effectiveness of a poorly soluble drug can be highly affected by its formulation design. In this respect, research on solid dispersion of hydrophilic carrier has commenced a decade ago to resolve the problem of poorly soluble drug. However, the availability of solid dispersion is commercially limited due to the concerns of its physical instability, unpredictability and inconsistency formulation performance. This is attributed to the lack of fundamental understanding on the processing method, physicochemical properties of the obtained solid dispersion. Therefore, better understanding on the processing methods and factors underlying the performance of solid dispersion may be required to maximize the use of solid dispersion. Hot melt extrusion (HME) method was introduced in formulating solid dispersion. The use of this production method offers many advantages such as environmental friendly, cost sparing and readily scalable production as compared to conventional methods. On the other hand, the hydrophilic polyvinylpyrrolidone (PVP) polymer with its good stabilising ability in the solid dispersion is less applied in HME process due to its possible degradation at high temperature. However, rejection on the use of PVP without thorough understanding of its potential might lead to underuse of this polymer in HME solid dispersion. This project explores the feasibility of using PVP and its derivative in HME manufacturing method. It offers an in-depth study on the hot melt processing, physical stability and dissolution behaviour of HME PVP-based solid dispersion. Factors affecting the production of fully amorphous solid dispersion and its physical stability are discussed, taking into account the influence of the composition and characteristic of the drug, drug-polymer interaction and the molecular weight of the polymer. In parallel, HME poorly soluble drug in PVP based solid dispersion were produced and investigated for their dissolution performances in order to understand the mechanism underlying the dissolution process of the HME PVP-based solid dispersion system