EVALUATION OF IN VITRO AND IN VIVO CORRELATION OF EXTENDED-RELEASE MICROSPHERES CONTAIN NALTREXONE

Background and Aim : Iran had a long history of Opium production. Iran has a major drug market, as well as a transit route of Opioids from the neighboring country, Afghanistan, to other regions.Clinically, there are two general treatment paths from which to choose, opioid maintenance treatment or detoxification. Agonist and partial agonist and Antagonist medications .A monthly intramuscular injection of naltrexone has received FDA approval for treatment of opioid dependence in 2011. In vitro release testing methods with good discriminatory ability are critical for quality control purposes and the development of methods that can be used in in vitro-in vivo correlation (IVIVC) are desirable to assist in formulation development and help reduce the regulatory burden of bioequivalence testing. Consequently, at this time, there are no standard compendial method(s) for in vitro release testing of extended release parenteral release dosage forms. The objective of the present study was to determine whether an IVIVC can be established for compositionally equivalent PLGA Naltrexone microspheres with manufacturing differences.Methods : Two compositionally equivalent formulations of naltrexone microspheres with different release characteristics were prepared using different manufacturing processes.The pharmacokinetics of the naltrexone microspheres were investigated using a The obtained pharmacokinetic profiles were deconvoluted using the Wagner-Nelson and AUC Fractional method, and compared with the in vitro release profiles of the naltrexone microspheres obtained using USP apparatus 2. Results : The results demonstrated that the developed USP 2 method was capable of detecting manufacturing process related performance changes, and most importantly, predicting the in vivo performance of naltrexone microspheres in the investigated animal model. a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1: 1 correlation between in vitro release and in vivo measurements confirmed the excellent Relationship between in vitro drug release and the amount of drug absorbed in vivo. Conclusion : Finally, a point-to-point correlation and level A was obtained for all three formulations. In addition, the comparison of the release profile of each formula showed that the qualitative properties of microspheres, such as particle size and drug accumulation, depends on differences in the manufacturing method.