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Solubility Enhancement of Theophylline Drug Using Mixed Solvency Approach

C Jaya Kumar, M. Dharmendira Kumar


“Solubility enhancement” is one of the difficult tasks that have become a great challenge in formulation development of orally administered drugs having poor aqueous solubility. Poor aqueous solubility of drugs creates significant problems in producing formulations of sufficiently high bioavailability, thereby preventing the effective usage of these drugs. With the introduction of the concept of “mixed-solvency,” it is feasible to increase the solubility of poorly water-soluble drugs in aqueous solutions containing blends of hydrotropic agents/co-solvents/water soluble solutes that provides synergistic enhancement effect on solubility of such drugs. In the present investigation, mixed-solvency approach is used to enhance the aqueous solubility of a poorly water-soluble drug “theophylline” (selected as a model drug), by making blends of randomly selected water-soluble substances from among the hydrotropic solutes (e.g., urea, sodium acetate), water-soluble solutes (e.g., PEG4000 and/or PEG6000); and cosolvents (e.g., PEG200, PEG400). The aqueous solubility of theophylline was observed at room temperature in randomly selected blends of solubilizers that contained varying combinations keeping the total concentration 50% (w/v) constant. Theophylline has λmax 274 nm and obeys Beers law in concentration range of 10–60 μg/mL. The results suggest that solubility of the theophylline containing blends of varying combinations was enhanced significantly using mixed solvency approach.

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