Prescription Technology Of Levamlodipine Besylate Tablets And Quality Standard Research

Amlodipine is a third-generation dihydropyridine calcium antagonist,which has remarkable curative effect on hypertension and stable angina pectoris.S-Amlodipineand R-Amlodipine possessed different pharmacological effects due to their stereo-configuration,only S configuration(levorotatory isomer)has hypotensive effect,yet R configuration(dextroisomer)would cause dizziness,headache,edema and other side effects.Therefore,Levoamlodipine(L-amlodipine)is the main component of antihypertensive drugs in clinic.The main preparations for Amlodipine are amlodipine besylate tablets and amlodipine maleate.In this research,L-amlodipine besylate was used as the raw material to prepare the tablets.The proportion of fillers,disintegrants,lubricants and other components in the auxiliary materials and the process route suitable for the actual production were studied,which laid a foundation for the realization of large-scale production.Upon the auxiliary materials of L-amlodipine were identified according to Norvasc,the compatibility experiments of the raw materials were carried out.The results showed that the active pharmaceutical ingredient(L-amlodipine besylate)were unstable at high temperature,and the related substances would increase by wet granulation process.Therefore,in this papar the comparative study between wet granulation process and powder direct tabletting process was carried out,which showed that the powder direct tabletting process was more feasible,and the related substances of the tablets were fewer than those of the tablets prepared by wet granulation process,displaying good stability,therefore the powder direct tabletting process was adopted.Finally,the proportion of each auxiliary material was determined by investigating the content of self-made products and original research products,related substances,content uniformity,dissolution curve,hardness,brittleness,disintegration time and other indexe,determine the ingredient.After the prescription is determined,the small-scale experiment was performed as following:the prescription dose of calcium hydrogen phosphate and sodium carboxymethyl starch are evenly mixed,then the mixture is evenly mixed with the levoamlodipine besylate in an equal amount progressive addition mode for three times.Adding a prescription amount of microcrystalline cellulose to continuously mix evenly,and finally adding the prescription amount of magnesium stearate to mix evenly.Single-punch press machine was used to prepare the tablets.The related substances,contents and dissolution test methods of small sample were determined,methodological verification was conducted respectively.After reproducing and enlarging the small-scale experiment,the pilot production process was finally determined.The pilot-scale amplification products were subsequently fully inspected.The factor tests,acceleration and long-term stability test were all carried out.The whole research process was compared with the original drug and Generic drug(Norvasc).In this paper,the levoamlodipine besylate tablets were systematically studied,and the formulation process suitable for mass production was screened out.The quality standards were studied and the related methodological validation was also carried out.Later inspection will be strictly in accordance with the established quality standards to control of product quality comprehensively and strictly,aiming to truly realize industrial production of the benzene sulfonic acid levoamlodipine tablets,and to produce safe and controllable,quality steady of drugs.