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Objectives In oral absorption of a drug, the drug first dissolves and then is absorbed by diffusion through gastrointestinal membranes. The gastrointestinal environment is aqueous in nature and it is well-known that one-third of the drug population is water insoluble. Hence, there is a need for enhancement of the solubility and dissolution of such drugs. In this work, enhancement of the solubility and dissolution of the practically insoluble drug glipizide was achieved by formation of bionanocomposites ( BNCs) using microwave-induced diffusion ( MIND), which ultimately leads to bioavailability enhancement. Methods BNCs were formed by using natural carriers such as gelatin, acacia, cassia and ghatti gum, with the help of microwaves. Selection of carriers was based on their surfactant and wetting properties. Solubility studies were carried out to establish the solubility-enhancing property of the BNCs. To support solubility analysis results, dissolution studies (i.e. powder dissolution and in-vitro dissolution) were carried out. The BNCs were characterized by Fourier transform infra-red spectroscopy, differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy and transmission electron microscopy. In-vivo performance of the optimised formulation was assessed by glucose-induced hyperglycaemia test in male albino Wistar rats. Key findings It was found that as the concentration of polymer in the composite increased the solubility and dissolution of glipizide were enhanced. The optimised ratio (drug : polymer) for all the composites was found to be 1:9. In the glucose-induced hyperglycemia test in rats, the optimized formulation demonstrated a significant reduction in hyperglycemia compared with a marketed formulation, Glynase. Conclusions The novelty of this work is the green and cost-effective way of forming drug nanocomposites with the help of microwave, which can be scaled up to an industrial level. The method gives an immaculate means of solubilisation by generating drug dispersion at the micro and nanoscale level in natural biodegradable stabilising media. Hence, this study demonstrates the use of BNCs in solubility and dissolution enhancement. [ABSTRACT FROM AUTHOR]