Solid Dispersion: An Alternative Technique for Bioavailability Enhancement of Poorly Soluble Drugs

Abstract

Formulation of solid dispersion in water-soluble carriers has been widely researched over the past four decades for solubility and related bioavailability enhancement. Despite 40 years of active research, there has not been much products in market based on this technique. The main reason for this being stability and scale up problems associated with this method, as reported by several authors. Strategies used for overcoming these problems and factors affecting formation of solid dispersion such as glass transition temperature and interaction of drug with polymer have been dealt conceptually in this review. The advent of surface-active carriers such as Gelucires, Poloxamers, and lipid-based carriers has given a new dimension for the successful development of solid dispersions by combating the problems associated with stability and also giving products with enhanced dissolution rate. Therefore, the article also discusses properties of such carriers that are being unraveled lately for formulation of solid dispersion. Characterization of solid dispersion to detect the change from crystalline to amorphous states and vice versa is an important tool for its formulation and determination of stability; thus, all the methods that are available for characterizations are discussed in this article with emphasis on the principle of the technique and its application.

Role of Viscosity in Influencing the Glass-Forming Ability of Organic Molecules from the Undercooled Melt State

“…Melt extrusion, whereby the active pharmaceutical ingredient (API) is co-melted with polymers and/or other excipients and extruded to produce a homogeneous amorphous dispersion has become more commonplace (3)(4)(5). Although solid dispersion technology has been studied for more than 40 years (6), to date, relatively few drug products have been marketed as amorphous solid dispersions (7). Major issues limiting the use of amorphous solid dispersions as a formulation technique include challenges with scale-up, in addition to concerns about API crystallization during the product shelf life.…”

Processing Impact on Performance of Solid Dispersions

“…Therefore, to make an insoluble compound orally bioavailable, a critical step is to achieve a fast dissolution and to maintain a high concentration of drug in the gastrointestinal milieu [ 1 , 2 ]. Over the years, various approaches have been developed to enhance the bioavailability of poorly water-soluble drugs, such as salt formation [ 3 , 4 ], nanoformulations [ 5 ], liquid capsule formulations [ 6 , 7 ], and amorphous formulations (neat drug or drug dispersed in polymer matrix) [ 8 , 9 ]. These approaches take advantage of solubility enhancement, particle size reduction, wettability improvement, or a combination of some of these features.…”

Nanoemulsion-based delivery systems for poorly water-soluble bioactive compounds: Influence of formulation parameters on polymethoxyflavone crystallization

“…The bioavailability of these compounds can often be increased by incorporating them within lipid-based delivery systems (Kohli, Chopra, Dhar, Arora, & Khar, 2010; Müllertz, Ogbonna, Ren, & Rades, 2010; Neslihan Gursoy & Benita, 2004; Pouton & Porter, 2008). A number of lipid-based delivery systems have been developed for this purpose, which vary in their compositions and structures: simple oil solutions (Burcham, Maurin, Hausner, & Huang, 1997); surfactant dispersions (Ali, Williams, & Rawlinson, 2010; Sinha, Baboota, Ali, Kumar, & Ali, 2009), microemulsions (He, He, & Gao, 2010; Rhee & Mansour, 2011); emulsions (Araya, Tomita, & Hayashi, 2005; Kawakami, et al, 2002; Poullain-Termeau, et al, 2008); self-emulsifying formulations (Barakat, 2010; Gao, et al, 2003; Neslihan Gursoy, et al, 2004; Setthacheewakul, Mahattanadul, Phadoongsombut, Pichayakorn, & Wiwattanapatapee, 2010; Yoo, et al, 2010); solid lipid nanoparticles (Muller, Mader, & Gohla, 2000; Wissing, Kayser, & Muller, 2004). …”