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Low-solubility, high-permeability compounds make up nearly one-third of all active pharmaceutical ingredients (APIs) in early development. For many compounds in this class, oral absorption can be achieved by enhancing solubility using solubilisation technologies. This article is an overview of current options in solid form solubilisation technologies, including several novel platforms that are based on nanocrystals and drug/polymer solid amorphous dispersions. The platforms discussed are spray-dried dispersions (SDDs), nanoadsorbates and crystallised spray-dried dispersions (CSDDs). Strategies are described to guide rational selection of the optimum technology for solubility enhancement.
Poor oral bioavailability due to the low aqueous solubility of potential drug candidates is an increasingly common challenge facing the pharmaceutical industry (1). Nearly one-third of compounds in early development have poor bioavailability due to low solubility, representing a significant loss in economic and therapeutic opportunity (2). Although they may not fit the ‘rule of five’, many of these low-solubility compounds – which fall into Class II of the Biopharmaceutics Classification System (BCS) – have the potential to be safe and efficacious, so it is critical that further development is not halted by solubility limitations (3).
In response to this problem, multiple drug-delivery technologies have been advanced in an attempt to solubilise such molecules in order to enhance their oral bioavailability. Solubilisation technologies can improve oral absorption of BCS Class II compounds by:
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Increasing dissolution rate
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Increasing concentration of dissolved drug (above the equilibrium concentration of the solubility of bulk crystalline drug)
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Maintaining the enhanced dissolved drug concentration
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