Abstract

DEVELOPMENT AND CHARACTERIZATION OF AMORPHOUS SOLID DISPERSION OF DARIDOREXANT FROM IMPROVED SOLUBILITY AND BIOAVAILABILITY

*Galhe Samruddhi Ashok, Mr. Tambade Yogesh B.

Abstract

This is because about 40 percent of the drugs and 70-90 percent of drug pipeline candidates have poor aqueous solubility, which interferes with oral bioavailability and therapeutic efficacy. Amorphous solid dispersion (ASD) technology has become a commercially viable approach, where the drugs are dispersed in the amorphous state in hydrophilic polymeric carriers to form high-energy states which lead to rapid dissolution and supersaturation. The present review is a systematic review of the basics of ASD such as the principles of thermodynamics, the idea of the spring-parachute effect in which amorphous drugs dissolve quickly (spring) and crystallization is prevented by polymers (parachute). Many polymeric carriers that are important (HPMC, HPMCAS, PVP, Soluplus, and others) are studied, with the criteria of selection being drug-polymer miscibility, molecular interactions, and glass transition temperature. Major preparation method spray drying and hot melt extrusion are compared in terms of scalability, thermal needs and commercial feasibility. Extensive characterization methods (DSC, XRPD, FTIR, dissolution testing) assure physical condition and performance. Mitigation strategies are used to solve critical stability issues such as the crystallization mechanisms and effects of moisture. A wide range of marketed products (Sporanox®, Zelboraf®, Kalydeco®) show clinical efficacy with a 2-10 fold bioavailability enhancement. Emerging trends are the mesoporous silica systems, 3D printing, and artificial intelligence application. ASD technology is still in its progress although there have been difficulties in predictive technology and scale-up; this technology is still in use as a pharmaceutical strategy to overcome solubility constraints in drug development.

Keywords: Amorphous solid dispersion, bioavailability enhancement, poorly water-soluble drugs, hot melt extrusion, spray drying, supersaturation, polymeric carriers.