Most of the drugs that are emerging from contemporary drug discovery programs are poorly water-soluble often present formulators with considerable technical challenges. The absorption of such compounds when presented in the crystalline state to the gastrointestinal tract is typically dissolution rate-limited, and the drugs are typically BCS class II or class IV compounds. The rate and extent of absorption of class II compounds is highly dependent on the performance of the formulated product. These drugs can be successfully formulated for oral administration, but care needs to be taken with formulation design to ensure consistent bioavailability. Essentially the options available involve either reduction of particle size (of crystalline drug) or formulation of the drug in solution, as an amorphous system or lipid formulations. The performance of amorphous or lipid formulations is dependent on their interaction with the contents of the gastrointestinal tract, therefore, a formulation exercise should involve the use of techniques which can predict the influence of gut physiology. A major consideration is the fate of metastable supersaturated solutions of drug, which are formed typically after dispersion of the formulation and its exposure to gastrointestinal digestion. A better understanding of the factors which affect drug crystallization is required, and the introduction of standardized predictive in vitro tests would be valuable. The use of a lipid formulation classification system combined with appropriate in vitro tests will help to establish a database for in vitro–in vivo correlation studies. For lipophilic drugs, which display dissolution rate-limited absorption, SEDDS may be a promising strategy to improve the rate and extent of oral absorption. Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsified drug can easily be absorbed through lymphatic pathways, by passing the hepatic first-pass effect.
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