Abstract

COMPARATIVE STUDY ON THE SOLUBILITY ENHANCEMENT OF POORLY WATER-SOLUBLE DRUGS USING SOLID DISPERSION TECHNIQUES

Chaitali S. Raut*, Shreyash Gosatwar, Sejal Khadse, Rupali Chavan

Abstract

The solubility of a drug significantly influences its bioavailability, therapeutic efficacy, and overall success as a pharmaceutical agent. Approximately 40% of new chemical entities (NCEs) identified through drug discovery programs exhibit poor water solubility, posing substantial challenges in drug development and delivery (Kalepu & Nekkanti, 2015). Poorly water-soluble drugs often demonstrate low dissolution rates in the gastrointestinal tract, leading to inadequate absorption and suboptimal therapeutic outcomes (Savjani et al., 2012). To address these challenges, various formulation strategies have been developed to enhance the solubility and dissolution rates of hydrophobic drugs. Among these, solid dispersion techniques have emerged as a promising approach. Solid dispersions involve dispersing poorly soluble drugs within a hydrophilic carrier matrix, resulting in improved wettability, reduced particle size, and, in some cases, transformation of the drug into an amorphous state, thereby enhancing solubility and dissolution rates (Vasconcelos et al., 2007). Several methods exist for preparing solid dispersions, including melting (fusion), solvent evaporation, and hot-melt extrusion. The melting method involves heating a physical mixture of the drug and carrier until it melts, followed by cooling to form a solid mass, which is then milled into powder (Dhirendra et al., 2009). The solvent evaporation method dissolves both the drug and carrier in a common solvent, which is then evaporated to yield a solid dispersion (Leuner & Dressman, 2000). Hot-melt extrusion, a more recent technique, involves the application of heat and pressure to mix the drug and carrier, forming a homogeneous solid dispersion (Maniruzzaman et al., 2012). The choice of carrier in solid dispersion systems is crucial for achieving the desired solubility enhancement. Hydrophilic polymers such as polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose (HPMC) are commonly used due to their ability to improve wettability and stabilize the amorphous form of the drug (Sekiguchi & Obi, 1961). Cyclodextrins, a class of cyclic oligosaccharides, have also been employed as carriers owing to their capability to form inclusion complexes with hydrophobic drugs, thereby enhancing solubility (Loftsson & Brewster, 1996). Despite the advancements in solid dispersion technology, challenges such as physical and chemical instability, scale-up difficulties, and reproducibility issues persist. Physical instability, particularly the recrystallization of the amorphous drug to its more stable crystalline form, can negate the solubility advantages gained through solid dispersion (Hancock & Zografi, 1997). Additionally, the selection of an appropriate preparation method and carrier is critical, as these factors significantly influence the stability and performance of the solid dispersion (Bikiaris, 2011). This study aims to conduct a comparative analysis of different solid dispersion techniques and carriers to enhance the solubility of poorly water-soluble drugs. By systematically evaluating various methods and materials, the research seeks to identify optimal strategies for solubility enhancement, thereby contributing to the development of more effective pharmaceutical formulations.

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