Mechanochemical Preparation Of Vitamin D₃ Instant Formulation

Vitamin D₃ is an essential vitamin for organism.However,its instability causes the inconvenience in production,transportation,storage and usage.It is important to investigate the efficient ways to improve its stability.This thesismainly aimed at increasing the stability and water solubility of vitamin D₃ by preparing the cyclodextrin inclusion compound and solid dispersion of vitamin D₃,respectively.And its formulations were studied.Chapter 1 introduced the physical and chemical properties,pharmacological action,clinical application of vitamin D₃.The concepts and application of inclusion compound and mechanical chemistry were also involved.Vitamin D₃-hydroxypropyl-?-cyclodextrin inclusion compound of different ratio of drug/excipient were prepared through the single factor test in chapter 2.The in-vitro dissolution test showed that inclusion compound can significantly improve the water solubility of vitamin D₃.The stability test results showed that the inclusion compound can significantly improve the light stability and high temperature stability of vitamin D₃.The formation of inclusion compound was verified by DSC and XRD analysis methods.In the third chapter,the vitamin D₃ inclusion compound tablets were prepared by direct compression method with the previously prepared inclusion compound as raw material and adding proper adjutants.After the optimizing the adjutants and prescriptions,the final prescription was determined as follows:0.8%of vitamin D₃ inclusion compound,2%of CMS-Na,1%of magnesium stearate,2%of micro powder silica gel,and 94.2%of lactose/microcrystalline cellulose.The compressed tablets had smooth surface.Its weight variation,friability,disintegration time and content uniformity all conformed to the pharmacopoeia standards.The compound of vitamin D₃ was prepared with Glycyrrhizic acid disodium by mechanical chemical technology in chapter 4.The optimized technological condition was determined as follows:rotational speed was 400rpm,ratio of drug/excipient 1:10?g/g?,and time 10 min.The solubility of the compound under this condition was 25.9 mg/mL,which was 6000 times the size of the vitamin D₃ raw materials?4.26?g/mL?.The prepared compound could significantly increase the high temperature stability of vitamin D₃,improve its light stability and long-term storage stability.But it had poor stability in aqueous solution,where it degraded 29%in 24 h.In-vitro dissolution test showed that the dissolution rate and solubility of the compound was rather high,where it is basically dissolved within 10 min.Finally,the formation of compound was verified by XRD and DSC analysis methods.