Formulation And Studies Of Sustained-release Core-in-cup Tablets Of Nifedipine

Objectives:Hypertension is a common disease. It can induce other severe diseases such as myocardial infarction, strokes. The complications and mortality can be dramatically reduced by blood pressure control. Nifedipine is a dihydropyridine calcium ion antagonist. It was developed by German company Bayer into the market. Nifedipine is a first-choice treatment for high blood pressure and angina after years of clinical application. Time to peak plasma concentration of Nifedipine normal preparations is 30 min and the plasma concentration changes enormously. Extended release nifedipine tablets are more effectively and safely. Extended release nifedipine tablets in the current market has a more steady drug release rate,but it isn't satisfactory. Osmotic pump tablets have constant drug release, but the technology is complicated. The purpose of this study is to prepare a Nifedipine core-in-cup tablets formulation, which can provide more smooth release of Nifedipine and the technology is simple and feasible.Methods:1 Preparation of sustained-release tablets of Nifedipine: Nifedipine mixed with NF8 B, NF9 A,MCC and melted in 65? thermostatic water bath, then cooled to semi-solid to granulate by 40 mesh. The prescribed amount of NF7 C, magnesium stearate and granule were mixed uniformly and compressed to prepare core tablets by 6mm die. EC M9 was added into 12 mm die,and the core tablet was put in the center, then compressed to prepare sustained-release core-in-cup tablet of Nifedipine.The best prescription and process of core tablets was determined by a series of single factor experiments and L9?3³? orthogonal experimental design.2 Research on quality control of sustained-release core-in-cup tablets of Nifedipine : established UV spectrophotometric method for the determination of dissolution of sustained-release core-in-cup tablets of Nifedipine and carried out the methodological studies, established HPLC method for the determination of Nifedipine and carried out the methodological studies.And studied the stability of the preparation with the evaluation indexes of appearance, content and dissolution.3 Developed a HPLC method for the determination of Nifedipine in Beagle dogs plasma. Betaloc was taken as the reference preparation, a single-dose,two-treatment,two-sequence and randomized crossover study was carried out on four adult beagle dogs, studying its pharmacokinetics, relatively bioavailability.Results:1The best prescription and preparation process of sustained-release core-in-cup tablets of Nifedipine were selected with release as the indicator.core tablets prescription: amout of 50 tabletsNifedipine 1.5gNF8B 2.75gNF9A 2gMCC?PH102? 1gNF7C 1.5gmagnesium stearate 1%Process: Nifedipine mixed with NF8 B, NF9 A,MCC and melted in 65? thermostatic water bath, then cooled to semi-solid to granulate by 40 mesh. The prescribed amount of NF7 C, magnesium stearate and granule were mixed uniformly and compressed to prepare core tablets by 6mm die.The preparation of core in cup tablets: EC M9 was added into 12 mm die,and the core tablet was put in the center, then compressed to prepare the sustained-release core-in-cup tablet of Nifedipine. Tablet hardness is 10¹5kg.Tablet coating: the core-in-cup tablets were coated to obtain sustained-release core-in-cup tablets of Nifedipine by 10% OPADDRY òXY. Pan speed: 25r/min, Pan temperature: 40?, coating weight gain:3%.2 Established a UV spectrophotometric method for the determination of dissolution rate of sustained-release core-in-cup tablets of Nifedipine. The detection wavelength was 238 nm with no interference of excipients, The methodological study results showed that within the concentration range of 1?g · mL^-1 12?g · mL^-1, the linear relationship between absorbance and concentration of Nifedipine was good. The regression equation was A=0.0566C+0.0165, correlation coefficient ?= 0.9998, RSD of precision value was 0.26%, low, medium, and high concentrations of recoveries mean of 100.8%. Nifedipine solution is Stable away from light. This method can be used for the determination of the dissolution rate of sustained-release core-in-cup tablets of Nifedipine.3 Established a HPLC method for the determination of content of sustained-release core-in-cup tablets of Nifedipine. The detection wavelength was 235 nm with no interference of excipients. The methodological study results showed that within the concentration range of 5?g · mL^-1 40?g · mL^-1, the linear relationship between peak area and concentration of Nifedipine was good. The regression equation was A=73572C+14320, correlation coefficient ?=0.9997, RSD of precision value was 0.12%, low, medium, and high concentrations of recoveries mean of 99.08%. Nifedipine solution is Stable away from light. This method can be used for the determination of the content of sustained-release core-in-cup tablets of Nifedipine.4 Study on stability of sustained-release core-in-cup tablets of Nifedipine:Under the condition of high temperature?60??, the tablets would soon melt. Under the conditions of high temperature?40??, RH 75%,strong light?4500Lx? and accelerated testing, there was no significant change in the appearance, content and dissolution. Under the conditions of wet RH92.5%, weight gain is over 5%. The preservation of the tablets should avoid high temperature and humidity.5 Established a HPLC method for the determination of Nifedipine blood drug concentration, Blank plasma was no interference on Determination of Nifedipine. In range of 2ng ·mL^-1 160ng·mL^-1,linear relationship was good, the regression equation was A=747.15C+1082.9, ?=0.9993, extraction recovery rate was more than 80%. Relatively bioavailability of test preparation was 94.60%.Conclusions: The formulation and preparation of sustained-release core-in-cup tablets of Nifedipine was simple and feasible, with good reproducibility. The tablets have constant drug release. The methods were established for the determination of content and dissolution.The tablets should be protected from high temperature and humidity.Vivo pharmacokinetic studies had shown that self-preparation had relatively high bioavailability.