A Research Paper on Optimization of Modified Release Gastro Retentive Once Daily Dosage Form of Apixaban and Predicting Pharmacokinetic Parameters
摘要
The aim of present study is to optimize once daily dosage extended release gastro retentive formulation of Apixaban and to predict in vivo pharmacokinetic parameters.
MethodsProposed formulation intended in the form of floating Multi-particulate system (Pellets) in order to ensure complete drug release in upper part of GIT. Gastro retentive floating pellets were manufactured by Fluid bed technology in which gas generating drug layering followed by extended release coating employed. Extended release coating was optimized using the Central Composite Face Centered design. In order to predict pharmacokinetic parameters, convolution method used and compare with reference product.
ResultsBased on the results, it is discern that % weigh gain and hypromellose concentration in extended release coating have significant impact on the studied responses. Analysis of the design space revealed that the batches with % hypromellose concentration from 62.5% to 67.5% and % weight gain between 12.5% and 13.5% at Triethyl citrate concentration between 18.8% and 22.8% would meet the desired responses. Predicted in-vivo pharmacokinetic parameters demonstrated that area under the drug concentration- time curve (AUC) of optimized once daily dosage forms is similar to twice dosage of reference product.
ConclusionSuggested results shows that optimized formulation could able to provide desire once daily dosage compared to conventional immediate release formulation having twice daily dosage. Hence, it is expected to have almost similar efficacy while reducing adverse effect profile.