Study On Oral Spray Of G-0601

G-0601 is an oral blood glucose-lowering drug used in the management of type 2 diabetes mellitus (also known as non-insulin dependent diabetes mellitus or NIDDM). Diabetes is a normal incretion disease, Type 2 diabetes represents about over 90% of all diabetes cases. G-0601 is approved at 1997, and is widely used from then on and its market has increase quickly for many years. For Type 2 diabetes patients, relieve the blood glucose is the first important task to avoid a serious of metabolic disturbance such as sugar, protein, fattiness, water and electrolyte etc. To improve patient compliance and develop new delivery, considering the physiochemical properties of G-0601 and the characteristics of oral spray administration, we planed to study on the oral spray of G-0601. Our scope and interest for the Study is to modify the pharmacokinetics of G-0601 in order to better suit larger sections of patients and increase its pharmaceutical administration forms.The very poor aqueous solubility gives rise to difficulties in the design of pharmaceutical formulations and lead to variable oral bioavailability. Improve the solubility of G-0601 and optimization of the formulation was the key work in our study. With the pH adjustment, cosolvents, surfactants; cyclodextrinsetc complex means, we examined the solubility enhancement of G-0601 using a serious of pure solvents and solvent mixture, and established solution method to evaluate the solubility of G-0601 with various materials.Based on the study above, the optimal formulation was determined. The pH-dependence of solubility can have useful application in the design of liquid and potential formulation. The result showed that the pH range of the Oral spray should be set at 7.0 to 8.0, according to the stability and solubility of the drug. The aqueous solubility of G-0601 could be enhanced significantly by using ethanol and polyethylene glycol as mixed-solvent systems. The solvent are generally considered safe for administration. After selection of solvent, pH, antiseptic and administration instrument, the formulation of the dosage form was determined.In order to control the quality of the preparation, a reliable HPLC method of determination of G-0601 and its relative substances was established. The stability study on oral spray indicated that it was stable, nearly without any changes during the stability study.The pharmacokinetics and bioavailability study of the oral spray of G-0601 was carried out on Beagle dogs in a randomized crossover manner. The drug plasma concentrations were determined by HPLC. The concentration-time curves don't conform to compartment model.Tmax was 30min and it's about half of oral administration formation. The relative bioavailability of the preparation was 120%. By pharmaceutical and pharmacological research of the G-0601 Oral spray in this research, it showed that the physical and chemical property of this Oral spray was stable and controllable in quality. Oral administration can produce quicker and better effect than oral administration of the same dose. These findings provided strong evidence for Oral spray use, a novel administration route of G-0601. The Oral spray of G-0601 could take effect quickly, which was faster than oral administration.