Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications

Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
International Journal of Pharmaceutics (Impact Factor: 3.79). 08/2011; 420(1):1-10. DOI: 10.1016/j.ijpharm.2011.08.032
Source: PubMed

ABSTRACT The poor oral bioavailability arising from poor aqueous solubility should make drug research and development more difficult. Various approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of poorly water-soluble drugs. To complete development works within a limited amount of time, the establishment of a suitable formulation strategy should be a key consideration for the pharmaceutical development of poorly water-soluble drugs. In this article, viable formulation options are reviewed on the basis of the biopharmaceutics classification system of drug substances. The article describes the basic approaches for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification. Literature-based examples of the formulation options for poorly water-soluble compounds and their practical application to marketed products are also provided. Classification of drug candidates based on their biopharmaceutical properties can provide an indication of the difficulty of drug development works. A better understanding of the physicochemical and biopharmaceutical properties of drug substances and the limitations of each delivery option should lead to efficient formulation development for poorly water-soluble drugs.

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    • "This is by far the most challenging case for the drug development as well as their formulation design. It is widely accepted, however, that formulation approaches similar to those for BCS class II drugs (improvement of the solubility and the dissolution behavior) could be practically applied to BCS class IV drugs, even though the absorption could be limited by the poor permeability after dissolving (Kawabata et al., 2011). One of the common procedures to improve the aqueous solubility of a drug is salt formation using a suitable counter ion. "
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    • "Compared with matrix materials such as Solutol 1 HS 15, Cremophor 1 RH 40 and Tween 1 80 (Strickley, 2004), Soluplus 1 can serve either as a solubilizer to form micellar structures in the aqueous medium or as a matrix material for solid dispersions. Moreover, Soluplus 1 based solid dispersions were demonstrated to significantly improve the solubility or oral bioavailability of poorly water-soluble drugs (Kawabata et al., 2011). "
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    • "Solid dispersion is one of the approaches to increase the dissolution rate of poorly water soluble drugs. Solid dispersion may be defined as dispersion of active ingredientswithinan inert carrier in solid state (Bhowmiket al., 2012; Leuner and Dressman, 2000; Kawabataet al.,2011; Chenet al.,2011). Solubility of LOV was increased by using solid dispersion techniques (Patel et al., 2008; Shaikh et al, 2011). "
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