Study On Nasal Spray Of Isosorbide Mononitrate

As the main biological active metabolite of Isoscrbide Dinifrate (ISDN), Isosorbide Mononitrate(5-ISMN)is one kind of commonly used medicine which treats coronary disease and the angina pectoris and has accurate curative effect after clinical uses for many years.The dosage forms of Isosorbide Mononitrate is mainly used on domestic and aboard clinical practice in the forms of injection and sublingual tablet. Intravenous administration of Isosorbide Mononitrate needs special environment and will cause some injury to patients. Sublingual tablet takes on action slowly and it is inconvenient for the patients to use. In order to act more quickly and improve patient compliance, considering the physiochemical properties of Isosorbide Mononitrate and the characteristics of intranasal administration, we planed to study on the nasal spray of Isosorbide Mononitrate.The prescription of Isosorbide Mononitrate nasal spray has been optimized. The enhancer was screened to enhance the absorption of the drug. It showed five kinds of enhancers had little effection on Isosorbide Mononitrate, so the enhancer was not added to the prescription. After selection of solvent, pH, antiseptic and administration instrument, the formulation of the dosage form was determined.A reliable HPLC method was established to control the quality of the Isosorbide Mononitrate nasal spray. the method is good accuracy and precision, and its linear range is 5~150μg·ml-1(r=1).The effect factor study showed that the index fluctuate was in the receivable range. The stability study on the prescription indicated it was stable, nearly without any changes. The toxicity and pharmaeokinetic and bioavailability were carried out on the Isosorbide Mononitrate nasal spray. The rabbit eyes and nose mucosal toxicity showed the prescription had no obvious toxicity. On the other hand, the pharmaeokinetics and bioavailability of Isosorbide Mononitrate nasal spray carried out on 6 Beagle dogs in a randomized crossover manner. The drug piasma concentrations were determined by HPLC. The concentration-times curves conformed to 2-compartment model with first-order absorption. Tmax and Cmax were 17.5min and 1994.70ng·ml-1 respectively. The absolute bioavailability of the preparation was 77.31%.In this paper, the results showed the quality of Isosorbide Mononitrate nasal spray stabile and controllable, stability, little ciliotoxicity and higher relative bioavailability etc., which basically met the aim and requirements of this study.