Study On Compound Alendronate Sodium Enteric - Coated Tablets

Osteoporosis is a kind of frequently-occurring diseases,which hits the old people,paticularly post-menopause woman.The symptoms of Osteoporosis contain the bone being fragile,bone fracture,and general dysostosis.Now to treat Osteoporosis we have developed a variety of drugs, which contain calcium,estrogenic hormone,diphosphonate,and vitamin D et al.Diphosphonate is a kind of artificial synthetical compound,using for clinic at 1970s,and it has the good qualities such as identified therapeutic effect and less adverse reaction.It has being a commonly used drug for osteoporosis instead of estrogenic hormone.Vitamin D is a common ancillary drug to prevent and treat Osteoporosis.On account of that treating osteoporosis needs a long peried of time,long term to take one variety drug may lead to more adverse reactions.For example long-term taking diphosphonate induces hypocalcemia,while vitamin D can promote calcium absorption,and raise up calcium level in blood.Association of diphosphonate and vitamin D can bring about synergistic action,and raise the bioavailability.When using vitamin D help treating osteoporosis or malnutrition,the dose of vitamin D₃ is low and controlled strictly,400IU/d.Vitamin D₃ is insoluble in water,slightly soluble in vegetable oil and labile to heat,light and oxygen.This article investigated the solubilization effect of hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin to vitamin D₃,and draw the phase equilibrium graph.The results indicate that hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin can raise the solubility of vitamin D₃ in water activly.The fitting curve is A_N type approximatly.We have chose HP-β-CD and vitamin D₃ to make inclusion complex,and the radio is 1000:1（HP-β-CD:vitamin D3,w/w）.Due to the instability of vitamin D3, the inclusion complex is prepared by lyophillization technology.The differential scanning calorimetric method was used for identification of the complex’s structure.Having investigated the stability of complex,vitamin D₃ entirely decomposes at 60℃,40℃and（4500±500）lx within 10d,while the degradation percentage of its complex with hydroxypropyl-β-cyclodextrin is less than 6%.Cores of vitamin D3 tablet and alendronate and vitamin D₃ complex tablet are determined based on the results of single-factor tests and orthogonal design tests.The tablets are prepared by powder direct compression.According to the pH of tablet releasing location and releasing media, we chose the Opadry^?enteric as enteric-coated material and the coating level of core tablets was 12%（w/w）.The dissolution rate of vitamin D3-HP-β-CD complex tablets increased 4 times than those which contain vitamin D₃ without inclusion.The vitamin D₃-hydroxypropy-β-cyclodextrin complex can improve considerably the stability and dissolution rate of vitamin D₃. The preparations are well quality-controlled and could meet the purpose and requirement of dosage form design.