Glibenclamide nanosuspension inhaler: development, in vitro and in vivo assessment.

Objective: The development of nanosuspension for targeted delivery of glibenclamide as hypoglycemic agent to the lung in an inhaler dosage form.Method: Glibenclamide nanosuspension formulations were prepared using Box-Behnken design to investigate the effect of independent factors on the dependent variables, Fourier-transform Infrared spectroscopy, Differential Scanning Calorimetry, evaluation of glibenclamide nanosuspension inhaler and in vivo hypoglycemic efficacy were performed to determine glibenclamide nanosuspension inhaler effect.Results: The results revealed that the mean particle sizes of the prepared nanosuspension ranged from 0.216 to 0.856 µm, zeta potential from +9 to +16 mV, the solubility ranged from 43% to 75%, the mass median aerodynamic diameter was 2.34 µm and the glucose level in rat was significantly reduced by about 60%.Conclusion: These results confirmed that glibenclamide nanosuspension inhaler enhance hypoglycemic effectiveness and reduce adverse effect of glibenclamide, opening up new dosage form in Diabetes mellitus treatment.

Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of glyburide and glipizide, two second-generation oral sulfonylurea hypoglycemic agents, are reviewed. Glyburide and glipizide are well absorbed after oral administration. The absorption of glipizide is delayed by food; in contrast, glyburide absorption does not seem to be affected by administration with meals. Both drugs are extensively metabolized by the liver. A two-compartment open model adequately describes the pharmacokinetics of these drugs. The apparent elimination half-life of glyburide in oral dosage forms available in the United States ranges from 7 to 10 hours. Glipizide has a terminal elimination half-life of 2-7 hours. The effects of renal and hepatic disease on the pharmacokinetics of glyburide and glipizide have not been well studied. Based on controlled, comparative studies in patients with new-onset, diet-failed, Type II diabetes, glyburide appears to be at least as effective as chlorpropamide and tolazamide in controlling blood glucose. Glipizide has shown efficacy comparable to or greater than that of chlorpropamide and tolbutamide. Glyburide and glipizide appear to be comparable in terms of their ability to control fasting blood glucose in Type II diabetics. The recommended initial dosage of glyburide in newly diagnosed Type II diabetics is 2.5-5 mg once daily. For glipizide, the initial dosage should be 5 mg once daily. Elderly or debilitated patients and those with renal or hepatic impairment should be started on lower dosages initially. Glyburide and glipizide have adverse effects that are similar to those observed with the first-generation oral hypoglycemic agents. Glyburide and glipizide do not appear to offer major therapeutic advantages over first-generation oral sulfonylurea hypoglycemic agents. However, they may represent therapeutic alternatives for some patients who do not respond satisfactorily to other sulfonylureas.