Enhancing drug solubility through advanced polymer extruded shellac-based matrix drug delivery systems

Abstract

The main objective of this study is to enhance the solubility of the model drug fenofibrate, by forming amorphous solid dispersions using a hot melt extrusion process. Hot melt extrusion offers an efficient way of increasing the solubility of a poorly soluble drug by forming amorphous solid dispersion. Shellac has potential as a pharmaceutical matrix polymer that can be used in extrusion processes, with further advantages for use in enteric drug delivery systems because of its unique pH-sensitive properties. The rheological property of a material affects the extrusion process conditions by their flow and deformation behaviour inside the barrel. However, there was a distinct lack of data on the processability of various shellac materials in the literature. Hence the initial step in this study was to explore various types of shellac and characterize their physicochemical and thermal properties along with their processability in the hot melt extrusion application. The analysis indicated that there was no chemical difference between the various shellac types compared in this study. It was found that the extrudable temperature ranges and rheological properties of different shellac types varied. SSB 55 Pharma FL had the lowest processing temperature and glass transition temperatures. Moreover, due to the shear-thinning behaviours, shellac can be extruded at lower temperatures. Subsequently, a prototype delivery construct was produced using hot melt extrusion which was based on fenofibrate as an amorphous solid dispersion, with shellac as the polymeric component. From the analysis of the data, enhanced solubility was achieved as evidenced by an increase in the dissolution rate of the drug in dissolution media. The amorphous solid dispersion formulation improved the solubility by over 8-times relative to untreated fenofibrate. The fenofibrate-shellac binary system provides a different approach from the traditional strategies and can be considered a convenient choice for optimising the oral delivery of fenofibrate. Moreover, a shellac base drug delivery system has an innate advantage due to its pH-sensitive nature and can be potentially used as a colon target delivery system. However, this section highlighted the disadvantages of a universal screw configuration due to insufficient mixing of the kneading section. The drug content in the drug formulation is varied, resulting in the error bar in the dissolution experiment being too large. In the dissolution experiment, the dissolution profile was similar when the maximum solubility of the drug in the aqueous solution was reached. Numerical simulation was used to understand the impact of two classical geometrical parameters on the mixing: the influence of different screw speeds and the stagger angles of a twin-screw extruder. The mixing performance was studied based on mixing characteristic parameters such as the maximum shear rate, stretching rate, mixing index, time-averaged efficiency, and residence time distribution. Based on these studies, it was found that the best mixing performance was achieved at a screw speed of 60 rpm. In the aspect of kneading block stagger angle parameters, the increase of stagger angle can promote the mixing performance of the extruder. On the contrary, the residence time increase with the increase of the stagger angle. Based on the simulation result, a new screw design was created and used to produce a new batch of drug formulations. The final section report, on amorphous solid dispersions of fenofibrate prepared with different types of shellac polymers and employing a hot melt extrusion process with optimized screw configuration. The predominant characteristics of the compositions were amorphous nature, reduced particle size, and improved uniformity, which resulted in an enhancement of drug dissolution and solubility. The rapid in vitro dissolution and the high degree of supersaturation demonstrated the success of these amorphous solid dispersion systems prepared by the hot melt extrusion process. The standard error of drug content, error bar in the dissolution and the SEM image confirmed the success of the newly designed screw configuration having a better mixing performance than the universal screw design.