The Preparation And Quality Control Of Sildenafil Citrate Dispersible Tablets

Objetive: Pulmonary hypertension is a complex haemodynamic and pathophysio-logical condition, mainly characterized with vasospasm of pulmonary arterioles,endometrial hyperplasia, and restructuring. Lung small artery blood vessels' growth and refactoring caused progressive increases in pulmonary vascular resistance,eventually leaded to right heart failure and death. In the past, the traditional oxygen therapy, diuretic, cardiac drugs, calcium antagonists and anticoagulant were used for therapy of pulmonary arterial hypertension. In some degree, it has been improving the patient's symptoms, raising the survival rate,but can't prevent the exacerbation. With the development of society, drug treatment of pulmonary hypertension developed from nonspecific vasodilation drug to the targeted drugs, from single therapy to multiple drugs combined and comprehensive treatment, greatly improving the symptoms and prognosis of the patients. Sildenafil is a selective phosphodiesterase type-5 inhibitor, acting by inhibiting the cyclic guanosine monophosphate degrading PD5 enzyme (which is heavily expressed in the pulmonary vasculature), thereby enhancing the effects of nitric oxide. Through relaxing pulmonary arterial vascular and improving it's refactoring, sildenafil can obviously increase the activity endurance of the patients with pulmonary hypertension and grade of cardiac function and improving hemodynamics indexes. At present, the commercial preparations are Film-coated tablets and injections at home and abroad, and sildenafil citrate dispersible tablets are not reported. This experiment was to prepare sildenafil citrate dispersible tablets which can rapidly disintegrating, rapidly having an effect. It can be used for the clinical first aid to quickly reduce the patients' pulmonary arterial pressure. Central composite design- Response surface methodology was used to get the final optimal prescription of sildenafil citrate dispersible tablets. And accurate and reliable quality control method was established to control the quality of homemade preparation and its stability by ultraviolet spectrophotometry and high performance liquid chromatography.Methods: In this trial, the central composite design-response surface methodology and single factor method were applied to screen and optimize the best prescription. First of all, through the single factor investigation about understanding the variety and dosage of dispersible tablets prescription of some accessories, and united star design-response surface optimization method, comprehensively studying the effect of relevant factors on the dispersion tablets. Using the dispersible uniformity and 15 min cumulative dissolution as evaluation indexes, the central composite design-response surface methodology was employed to optimize the amount of materials.Simultaneously, as sildenafil citrate dispersible tablets to establish accurate and reliable method for quality control. Selects the UV and HPLC methods to dispersed tablet of homemade test. While referring to "Chemical stability study technical guidelines" and the characteristics of sildenafil citrate, the implementation of strong acid, strong alkali, strong oxidizing damage test, according to the influencing factors for the optimal prescription test, accelerated test and long-term test, for the study of the prescription design, process improvement, quality, packaging, transportation,storage, such as the provision of relevant information.Results: The final prescription was confirmed as the following. In the sildenafil citrate dispersible tablets, the compositions of sildenafil citrate are 70.24 mg, MCC,lactose, CaHPO4-2H2O and CCNa inside the particles were 110, 95, 50 and 30 mg,CCNa and magnesium stearate outside the particles were 40 and 4.76 mg.The method for quantitative determinations established by ultraviolet spectrophotometry and high performance liquid chromatography was accurate and reliable. Chromatographic conditions of sildenafil citrate is determined as : choosing reverse silica gel KromasilC18 chromatographic column (200mm×4.6mm, ?m);velocity detection wavelength was set at 290 nm, the flow rate was set to 1.0 mL/min,column temperature was controlled at about 35 0C,and mobile phase is methanol:0.05M triethylamine phosphate (taking 7 ml triethylamine diluted to 1000 ml and using phosphoric acid adjust the PH to 3.0): methanol and acetonitrile (50:30:20). At the chromatographic conditions, sildenafil citrate in 5.25?42.00 ?g/mL within the scope of linear good, high accuracy and good precision. Results show that this method is accurate, specific, and can be used for content determination of the sample.The sildenafil citrate bulk drug and formulations were stable to strong acids and alkalis and unstable to strong oxidizing. The influencing factors results showed that:high temperature, high humidity conditions were all affecting the sildenafil citrate dispersible tablets. Therefore, suggesting that the tablets should be sealed packaging and stored in a cool and dry place. Long-term test has only conducted to 12 months.In the meanwhile, various examining indexes of the preparations were meeting related requirements, showing basic stability. The expiration period was to be tested further to complete.Conclusion: This topic selected optimization of sildenafil citrate dispersible tablets preparation methods, homemade tablet properties is good, content uniformity,and commercially available compared sildenafil citrate tablets, dissolution behavior increased significantly. To determine the HPLC method is a good specificity, easy to use, can be used to detect the content of sildenafil citrate.