处方工艺研发报告模板-vitamin B 片剂

DEVELOPMENT OF THE PRODUCT(STUDY OF PREFORMULATION OF THE PRODUCT) OBJECTIVETo Obtain tablets of Vitamin B complex tablets that complies with National standard. SELECTION OF MATERIALSelection of Active ingredient1.Thiamine HydrochlorideManufactured in Hubei Huazhong Pharmaceutical Co., Ltd. and complies with British Pharmacopoeia 2007. Thiamine hydrochloride is a white or almost white, crystalline powder, freely soluble in water, soluble in glycerol, slightly soluble in alcohol.2. Pyridoxine HydrochlorideManufactured in Zhejiang Tianxin Pharmaceutical Co., Ltd. and complies with British Pharmacopoeia 2007. Pyridoxine Hydrochloride is A white or almost white, crystalline powder, freely soluble in water, slightly soluble in alcohol. It melts at about 205 °C, with decomposition.3. CyanocobalaminManufactured in Sichuan Pharmaceutical Co., Ltd. and complies with British Pharmacopoeia 2007. Cyanocobalamin is A dark-red, crystalline powder or dark-red crystals, sparingly soluble in water and in alcohol, practically insoluble in acetone. The anhydrous substance is very hygroscopic.Selection of excipientsBelow are reviewed in the formula selection: Maize starch, Sucrose, Dextrin, Hipromellose, Magnesium Stearate and Microcristalline Cellulose. All the ingredients complies with Bp or USP standards.Selection of coating materialThiamine hydrochloride, Pyridoxine Hydrochloride and Cyanocobalamin are hygroscopic, so we select the film coating material to protect the active ingredients. Coating the tablets use the film coating powder manufactured by Zhejiang Xinhua Pharmaceutical Co., Ltd. and Tianjin ILE Pharmaceutical Materials Co., Ltd.Coating as normal according to the film-coating technicsCoating solution 1: manufactured by Zhejiang Xinhua, add into Purified water, agitate45 minutes to prepare 8% coating solution.Coating solution 2: manufactured by Tianjin ILE, add into Purified water, agitate 45 minutes to prepare 12% coating solution.Test:Heat-resistance test of coating film: tranfer tablets coated by solution 1 and solution 2 respectively into 80 oven for 3 hours, take out and observe the film change quickly. Moisture proof, water proof test . Separate put the tablets 20 tablets coated by the two coating solution under the circumstances of 25ºC RH75% and 25ºC RH92.5%, sample termly, weigh, calculate the moisture absorption.Tablets 5 Results of moisture proof, water proof testPercentage of moisture absorption %Coating RH75% RH75% RH75% RH92.5% RH92.5% RH92.5%Material 3 days 5 days 10 days 3 days 5 days 10 daysSolution 1 1.85 1.92 2.25 3.24 3.85 3.94Solution 2 2.44 2.63 2.94 3.96 4.55 5.13Dissolution test: For each type of the coated tablets, carry out the dissolution test respectively with 6 tablets, calculate the cumulated dissolution percentage.Table 6 Results of dissolution testTime min Percentage of cumulated dissolution % IngredientCoating Solution 1 Coating Solution 245 minutes 93.25±0.57 92.87±0.59 Thiamine 45minutes 93.12±0.74 93.23±0.81 Pyridoxine 45 minutes 90.02±0.85 89.44±0.82 CyanocobalaminConclusion coating solution 1 gives better performance in aspects as heat.resistance, moisture proof, water proof and dissolution of Cyanocobalamin, and tablet tabletsurface is more smooth and uniform. So we adopt the coating solution 1, that is 8%coating solution, powder manufactured by Zhejiang Xinhua Pharmaceutical Co., Ltd. According above stated, we confirm the formula and manufacture process of Vitamin B complex tablet1.3 Process validationManufacture 3 batches sample as the formula, the preparation and quality are listed in table 7 and 8, which indicated that the tablets quality is good and stable and the formula reproducibility is good and suited to amplificatory production.Table 8 Quality review of the three batches pilot-scale sampleDissolution In 45 minutes(%)Batch number Character Thiamine Pyridoxine CyanocobalaminFilm-coated tablets which0301112 appear almost white after 93.3 92.8 90.5Removal of the film.Film-coated tablets which0301113 appear almost white afterRemoval of the film. 93.3 92.9 90.2Film-coated tablets which0301114 appear almost while afterremoval of the film 93.2 92.8 90.1Manufacture the medicine according to the fomula, the batch size is 100,000 tablets, manufacture 3 batches totally. Test the dissolution respectively and compare with the commercial tablets. (See dissolution curve below).Chart 1 Dissolution curve of Vitamin B complex tablets and reference tablets Conclusion: There is no obvious dissolution difference between self-manufactured tablets and commercial tablets.Test Samples: Vitamin B Complex tablets, 3batches manufactured by our laboratory Reference Samples: CO-VB tablet, a market available productDissolution curve of Thiamine：Dissolution curve of Pyridoxine：Dissolution curve of Cyanocobalamin：1.4 Influence factor testCarry out the influence factor test to the sample with batch number 0301112 and 0301113. Consider the property of the active ingredients, we set the temperature at 40℃ , RH 75%, Lighting at 5000Lx to carry out the rest, review the formula stability.Sample source Remove of 40℃ RH75%±5%, lighting 5000Lx for 10 days,test at the fifth day, tenth day. (see table 9)Review items Character assay related substances, disintegration.Table 9 Result of influence factor testConclusion: The influence factor test indicates that the indexes of the product changes a little under high temperature, high humidity and lighting but all the indexes are in the accepted range. So the product should be protected from light, preserved at well sealed, dry place.1.6 General equipmentsSHK 220B wet mix granulator DP-30A tablets pressGZPK 138 tablets pressTNW200-500 coating machine JB-A friability testerRCZ 8A dissolution tester。