IAJPS 2017, 4 (01), 95-102 Y.Narasimha Reddy et al ISSN 2349-7750 www.iajps.com Page 95 CODEN (USA): IAJPBB ISSN: 2349-7750 INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES Available online at: http://www.iajps.com Research Article EVALUATING THE EFFECT OF DIFFERENT PLGA MICROSPHERE PREPARATION METHODS ON PHARMACOKINETICS OF EXENATIDE Harish Kaushik Kotakonda 1, 4 , Malothu Nagulu 2 , Narasimha Reddy Yellu 3* 1 Dept of Pharmacy, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad, India. 2 Dept of Pharmacology, Swami Ramananda Thirtha College of Pharmaceutical Sciences, Nalgonda, India 3 Dept of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India. 4 Dept of Drug Metabolism & Pharmacokinetics, JVR Biosciences, Hyderabad, India. Received: 31 December 2016 Accepted: 31 January 2017 Published: 05 February 2017 Abstract: Solvent extraction and Co-solvent method have been widely used methods for preparation of Poly (DL-lactic-co-glycolic acid) (PLGA) microspheres. However there were no reports on evaluating the effect of different PLGA microsphere preparation methods on exenatide release and it’s corresponding pharmacokinetics. Four different exenatide PLGA Microspheres ie HSE, USE, SoEX and COS were prepared by following four different approaches. All the four different exenatide PLGA microspheres, solution and Bydureon ® was administered through subcutaneous route to male Sprague Dawley rats at different dose. Plasma samples were analysed using LC/MS method. The highest initial burst release was achieved by SoEx MS formulation whereas the transient second burst was observed higher for COS MS formulation. It was observed that that even though the drug release was controlled by polymer degradation, the internal structural changes of microspheres played the most important role than the decrease of polymer Mw. The cumulative release of exenatide from HSE based microspheres was similar to COS MS and higher among the other treatment groups. Upon dose normalization and comparing the peak maximum concentrations (Cmax) achieved by microsphere formulations with Bydeuron group for COS, HSE, SoEX, USE group was 12.4X, 28.5X, 40.3X and 6X higher whereas the exposure (AUC0-t) achieved by microsphere formulations compared with Bydeuron group for COS, HSE, SoEX, USE group was 7.3X, 3.4X, 2.8X and 2.8X higher. The detailed PK based evaluation of PLGA based microspheres prepared by different methods in the study provide help in guiding the emulsion-microsphere preparation or other long-effective release systems and also the results of the study reveals another important point that invitro release behaviours of these microspheres were not influenced by different preparation methods but was affected by internal structure evolution. Therefore, COS MS can be evaluated further for developing a once-in-a 2weeks injection of COS MS to replace a BID daily injection of exenatide. Key Words:Exenatide; PLGA microspheres; Subcutaneous Route; Bydureon Corresponding Author: Prof. Y. Narasimha Reddy, Head, Dept of Pharmacology UCPSc, Kakatiya University Warangal, Telangana India-506009 Email:ynrku@yahoo.co.in Please cite this article in press asY.Narasimha Reddy et al, Evaluating the Effect of Different PLGA Microsphere Preparation Methods on Pharmacokinetics of Exenatide, Indo Am. J. P. Sci, 2017; 4(01). QR code