Solubility Enhancement Strategies for BCS Class II Drugs in Orally Disintegrating Tablet Platforms: A Review
Abstract
Objective(s): To critically review and synthesize solubility enhancement strategies applied to Biopharmaceutics Classification System (BCS) Class II drugs formulated as orally disintegrating tablets (ODTs), with particular attention to how dissolution-rate-limiting solubility constraints are addressed without compromising the rapid disintegration performance that defines this dosage form.
Data sources: Peer-reviewed primary and review literature (2013-2026) on BCS classification, solid dispersion technology, sublimation- and lyophilisation-based pore-forming techniques, particle size reduction and nanocrystal engineering, cyclodextrin complexation, and self-emulsifying systems, together with published formulation and evaluation studies on rapid-melt ODTs of representative BCS Class II lipid-lowering agents.
Study selection: Publications addressing the mechanistic basis of solubility enhancement, its integration with ODT manufacturing platforms (direct compression, sublimation/lyophilisation, solid dispersion, nanocrystal freeze-drying), and comparative in vitro performance (disintegration time, dissolution efficiency, drug release) were prioritized, including case-level formulation studies on rosuvastatin, simvastatin, and ezetimibe rapid-melt systems, supplemented by recent (2021-2026) literature to reflect current developments in the field.
Summary of contents: This review outlines the biopharmaceutical rationale for combining solubility enhancement with ODT technology, describes the principal solubility enhancement strategies (solid dispersion, sublimation-assisted pore formation, particle size reduction/nanocrystal engineering, cyclodextrin inclusion complexation, and surfactant/self-emulsifying approaches), and examines their integration into ODT matrices through a series of case studies on statin and cholesterol-lowering rapid-melt formulations, together with recently reported BCS Class II ODT systems. Evaluation parameters specific to solubilized-drug ODT systems, formulation-process trade-offs, regulatory considerations, and future directions are also discussed.
Conclusion: The convergence of solubility enhancement technology with ODT platforms offers a rational route to improving both the dissolution rate and patient acceptability of BCS Class II drugs, provided that the porosity and disintegration performance of the tablet matrix are preserved during incorporation of the solubilized drug intermediate.
Keywords: BCS Class II; solubility enhancement; solid dispersion; orally disintegrating tablets; rapid melts; sublimation; nanocrystal; dissolution rate
Keywords:
Fast dissolving oral film, Oral disintegration tablets, BCS Class II Drug, amorphous solid dispersion, solubility enhancement, sublimation, nanocrystal, dissolution rateDOI
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