The Preparation And Quality Control Of Gliclazide Sustained-Release Capsules

Objectives:The purpose of this topic is to develop gliclazide24h sustained-release capsules to reduce the number of medication.Establish the quality control method and the quality standards for gliclazide sustained release capsules,and study on stability of homemade preparations.Methods:Based on the dosage form and principle of sustained-release capsules,we screen the process method.At first,we screened the type and amount of the drug-containing pellets accessories,used L9(34)orthogonal experiment to optimize the preparation process,and used single factorvisits to inspect the preparation process.According to the micromeritic characteristics of drug-containing pellets and the percentage of cumulative release,we determined better prescription and process.Once more,we screened the type and amount of the accessories of film coating,by using single factor.According to the percentage of cumulative release of the coated pellets and comparing the F2 value with control preparations release behavior,we determined the better coating prescription and coating process.At Last,According to the best prescription we prepared sustained-release capsules.According to the Chinese Pharmacopoeia,relevant standards and the reports in the literatures to establish the content of gliclazide sustained-release capsules,method for determination of related substances and release,and verify the methodology.Reference to the State Food and Drug Administration guidelines for stability of new drugs and the actual situation and the stability tests,we inspected the influence of high light,high temperature,high wet on the bulk drugs and pellets,and had some accelerated tests and long-term test.Results:Every capsule is 140mg.At first we prepared drug-containing pellets,and then prepared coated pellets.Mixture Gliclazide 30mg,PVP K29/30 3.5mg,MCC 10mg,Mannito 90mg,and add the right amount of water as a wetting agent to make of soft material,20mesh granulation.Put these into the centrifugal rounded machine and keep granules rounding 6 min in the condition of 500 rpm and minimum blast.Dry the drug-containing pellets at 50 ℃ after adding talcum powder 1.86mg.Use the fluidized bed to make drug-containing pellets coated.The coating solution is 1%EC and 0.25%PEG6000 of 80%ethanol solution.The coating parameters are fan frequency of 30Hz,the inlet air temperature of 50 ℃,the liquid jet speed for 1.5 ml-min-1,atomization pressure of 0.05 MPa.Coating weight gain 2%.After coating was completed,add the talcum powder 1.86mg and dry coated pellets at 40℃ blast drying.Determination of content and related substances and release both use UV-HPLC method,the methodology validation determination method is accurate and reliable.The chromatographic conditions of content assay and related substances are as follows,chromatographic column for Eclipse XDB-C 8(4.6 X 150 mm,5μm)using acetonitrile-water-triethylamine-trifluoroacetic acid(39:61:0.1:0.1)as mobile phase,detection wavelength of 235 nm.Column temperature of 35℃,the flow rate of 1.0 mL min-1,sample amount to 20 μL.Three group of samples of content and related sub stances results meets the requirements.Release method of the preparation:PBS 7.4 solution,release medium volume of 900 mL,Rotating basket method,rotation speed of 100 rpm,the temperature of 37℃±0.5℃.States:cumulative dissolution percentage of the drug-containing pellets at 60 min should not be less than 90%.The cumulative release percentage of coated pellets at 2h,4h,12h are 17 to 31%,35%to 55%and more than 75%.Releases of three batch samples are comply with regulations.Compared with the original development agent,similar factors were greater than 50.Release mechanism of the research results shows that drug release behavior in vitro of the homemade gliclazide sustained-release capsules and the original drugs are both consistent,including both use Higuchi model as the best drug release model.The n = 0.7813 that Ritger Peppas model fitting of homemade sustained-release capsule are between 0.45 and 0.89,shows that the release of the drug is the mixed diffusion mechanism,namely the synergy results of drug diffusion and frame dissolution.The results of the influencing factors showed that:high temperature,high humidity conditions and bright light on the stability of gliclazide sustained release capsules,therefore suggesting that the capsules should be sealed packaging,dark cool place.Preparations selection of sealed packaging,cool dark place preserve the basic stability of accelerated tests and long-term experimental conditions.Accelerated test:the three batches of gliclazide sustained-release capsules sealed packaging,at 40 ℃±2℃,RH = 75%±5%,for 6 months.The results showed that the preparation of the inspection indicators is in line with the relevant provisions of this product quality standard,the basic stability.Long-term test:three batches of sealed packaging gliclazide sustained-release capsules at 25 ℃ 2 ℃,RH = 60%± 10%under the conditions of storage.6 months assessment results showed that the preparation of the inspection indicators is in line with the relevant provisions of this product quality standard,the basic stability.The stability aftet Six monthsr of long-term trial is continuing.Conclusion:Through the selection and optimization of gliclazide,we have got gliclazide sustained-release capsule prescription and process.The pellets have good traits,the cumulative release percentage meets the requirements,f2>50,the release behavior is similar with the control preparations.HPLC method is specific and simple,and can be used for the preparation of the content determination and related substances.