Advances in Oral Drug Delivery for Poorly Soluble Drugs: Formulation Technologies and Biopharmaceutical Approaches
DOI:
https://doi.org/10.69980/mr2heg16Keywords:
Poorly soluble drugs, Oral drug delivery, Formulation technologies, Bioavailability, BiopharmaceuticsAbstract
Poor aqueous solubility is a major constraint on oral drug development because inadequate dissolution can limit intestinal absorption and produce variable systemic exposure. This study compared formulation technologies and biopharmaceutical determinants of oral performance using a synthetic dataset comprising 240 poorly soluble drug formulations and 25 physicochemical, formulation, dissolution, permeability, pharmacokinetic, and stability variables. Ten formulation approaches were evaluated, including amorphous solid dispersions, nanocrystals, micronization, cyclodextrin complexes, co-crystals, lipid-based formulations, self-nanoemulsifying drug delivery systems, polymeric nanoparticles, mesoporous silica carriers, and crystalline references. Descriptive statistics, Kruskal-Wallis testing, Spearman correlation analysis, and multivariable regression with robust standard errors were applied. Formulation technologies differed significantly across key performance measures, including apparent solubility, dissolution, supersaturation, precipitation inhibition, fraction absorbed, bioavailability, and stability. Advanced enabling systems generally showed improved dissolution and systemic exposure relative to crystalline references. Supersaturation was positively associated with absolute bioavailability, while multivariable modeling indicated that oral exposure reflected coordinated effects of dissolution, solution-state behavior, permeability, and absorption rather than solubility alone. These findings support mechanism-based formulation selection integrating physicochemical and biopharmaceutical properties. Experimental validation using biorelevant dissolution, permeability, precipitation, and pharmacokinetic studies is required before applying the observed relationships to drug products in practice. These results provide a framework for development.
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