Correlation Between In Vitro Release And In Vivo Absorption Of Naltrexone Implants

Objective:To investigate the regularity of the in vitro release of naltrexone implants; to establish a quality standard in vitro bioavailability, and as a quality control indicator in the preparation mass; through in vitro in vitro release to test in vivo determination method is reasonable, and to find possible in vitro release conditions to predict in vivo absorption, and to study the release mechanism of naltrexone implants in vitro and in vivo.Methods:Reference to the guiding principles of the2010edition of Chinese Pharmacopoeia Appendix and using accelerated testing in vitro to study the in vitro release of naltrexone implants. And the following conditions of release were studied:the media to release, sampling points, speed, basket method and the slurry method, burst release point.Through release experiments of the three batches to examine the reproducibility and uniformity; through the zero, one, the Higuchi and Ritger-Peppas equation model to study the in vitro release mechanism of naltrexone implants; implanted three naltrexone implant batches at the same time in the back of rats, remove the residual film in1,3,5,10,15,30,45,60,75,90d, respectively, established an HPLC method for determination of the content of residual piece, and using the zero, one, the Higuchi equation and Ritger-Peppas equation to study in vivo absorption and its mechanism of naltrexone implants in rats; introduced the correlation coefficient K(R) to adjust the experimental sampling time in vitro release, to establish the correlation between in vitro release and in vivo absorption.Results:established UV-visible spectrophotometry method to determine the content and release of the naltrexone in naltrexone implant; established in vitro release method of the naltrexone implant;according to the release model fitting, three batches of naltrexone implants are zero level release; established HPLC determination of the content of naltrexone in the residual film of rats, three batches of naltrexone implants are zero level release; through study the section of the Ritger-Peppas equation and its modified, it indicated that the release mechanism of naltrexone implants fist is Fickian diffusion, late id skeleton dissolution; the in vitro-in vivo correlation equations of the three batches of samples, respectively:Pvivo=0.9113Pvitro-1.4827, r=0.9833, Pvivo=0.8129Pvitro+8.5974, r=0.9734, Pvivo=0.7749Pvitro+3.8767, r=0.9554, r is greater than the critical correlation coefficient. Therefore the in vitro release-in vivo absorption rate is significant.Conclusion:Using in vitro release rate-in vivo absorption rate of naltrexone implants to evaluate the correlation between in vitro and in vivo, the results of all proved the naltrexone implants in vitro and in vivo was significantly and showed a zero order release,and in vivo release mechanism dominated by diffusion, after the dissolution is mainly. Release experiments were scientific, simple, reasonable, and could provide a guarantee to controllability of the intrinsic quality of the naltrexone implants...