Study On VD₃ Self-microemulsified Calcium Effervescent Granules

Objective:As calcium supplements,vitamin D3?VD3?and calcium carbonate synergistically promote the absorption of calcium.VD₃ is sensitive to temperature and light and has poor stability.At the same time,due to its low content,it was difficult to be mixed evenly,which was the problem that needs to be solved for calcium supplement.The self-microemulsion drug delivery system can significantly improve the solubility and stability of the drug.In this paper,using VD₃ self-microemulsion as intermediate,effervescent preparation and self-microemulsion drug delivery system were combined to prepare VD₃ self-microemulsion calcium effervescent granules.Methods:In the preparation of VD₃ self-microemulsifying,the solubility experiment and pseudo-ternary phase diagrams test were used to screen the prescription.The self-emulsification time and particle size were used as the evaluation indexes to optimize the prescription using central composite design-response surface methodology.In the preparation of VD₃ self-microemulsifying calcium effervescent granules,hygroscopicity,particle size,water content,drying time and main component content were used as evaluation indexes to screen the prescription and process parameters.The content detection methods of VD₃ and calcium carbonate were established and verified.According to the guiding principles of drug stability test,the influencing factors and accelerated test were studied.Results:Among the prescriptions of VD₃ self-microemulsifying,the optimal prescription was ethyl oleate,KolliphorRH40 and propanediol,and the mass ratio was0.2:0.53:0.27.In the optimal prescription of granule,the filler was maltodextrin and mannitol?the mass ratio was 3:1?,the effervescent agent was citric acid,and the flavoring agent was orange essence?the dosage was 1%?.The preparation process was as follows:The VD₃ self-microemulsion was used as the adhesive after being diluted with ethanol,then mixed with calcium carbonate and pharmaceutical necessities evenly,added with adhesive to make soft material.Effervescent particle was made through an 18-mesh sieve and dried at 50?for 2 hours.The obtained VD₃self-microemulsifying calcium effervescent granules met the requirements of Chinese Pharmacopoeia.The HPLC method for the determination of VD₃ was established,the linearity,precision and recovery of VD₃ met the requirements.The content of calcium carbonate was determined by titration method,which was verified by methodology and had high accuracy.The VD₃ self-microemulsifying calcium effervescent granules were tested by influence factor test and acceleration test,all the indexes met the requirements and the stability was good.Conclusion:A VD₃ self-microemulsifying calcium effervescent granule was successfully prepared in this paper.By using central composite design to optimize the prescription,the method of preparing VD₃ self-microemulsion was simple,the solubility of drug was high and the stability was good.In vitro drug release test showed that the dissolution was significantly higher than active pharmaceutical ingredient,VD₃ self-microemulsifying prescription can be used as intermediate and final product.The stability of VD₃ self-microemulsified calcium effervescent granules was good,which provided a reference for industrial production.