: Glipizide (GZ) is an oral blood-glucose-lowering drug of the sulfonylurea class characterized by its poor aqueous solubility. Aiming for the production of GZ tablets with rapid onset of action followed by prolonged effect; GZ-Polyethylene glycol (PEG 4000 and 6000) solid dispersions with different ratios, (using melting and solvent evaporation method), as well as, coprecipitate containing GZ with polymethyl-methacrylate (PMMA) were prepared. Four tablet formulations were prepared containing; a) GZ alone, b) GZ: PEG6000, 1:10, c) GZ:PMMA 1:3, and, d)both GZ:PEG6000 1:10 and GZ:PMMA 1:3. The solvent evaporation method showed more enhancement of GZ solubility than the melting one, and this solubilizing effect increased with PEG increment. Generally, PEG6000 showed more enhancement of dissolution than PEG4000 especially at 1:10 drug: polymer ratio (the most enhancing formula). Also, the prepared tablet formulations showed acceptable physical properties according to USP/NF requirements. The dissolution results revealed that tablets containing PEG6000 (1:10) have the most rapid release rate, followed by the formula containing both PEG6000 and PMMA, while that including PMMA alone showed the slowest dissolution rate. Moreover, In-vivo studies for each of the above four formulations, were performed using four mice groups. The most effective formula in decreasing the blood glucose level, through the first 6 hours, was that containing GZ and PEG6000, 1:10. However, formula containing the combination of enhanced and sustained GZ was the most effective in decreasing the blood glucose level through 16 hours. Successful in-vitro in-vivo correlations could be detected between the percent released and the percent decreasing of blood glucose level after 0.5 hours.
Blood Glucose Prediction with Variance Estimation Using Recurrent Neural Networks
