In vivo performance evaluation and establishment of IVIVC for osmotic pump based extended release formulation of milnacipran HCl Punit B. Parejiya * , Bhavesh S. Barot, Hetal K. Patel, Mehul R. Chorawala, Pragna K. Shelat, and Arunkumar Shukla K. B. Institute of Pharmaceutical Education and Research, Gandhinagar, India- 382023 ABSTRACT: The objective of the present study was to carry out a pharmacokinetics evaluation of an oral modified release formulation [Aquarius EKX 19102 SRX–2 based osmotic pump (OP)] containing highly soluble milnacipran HCl (MH) as a model drug. It was also aimed at developing an in vitro–in vivo correlation (IVIVC) model for a developed OP. In vivo plasma concentration data were obtained from six healthy male New Zealand albino rabbits after administration of immediate- release milnacipran HCl solution (IRMHSOL) and milnacipran HCl osmotic pump (MHOP). In vitro samples were analysed using an in house developed spectrophotometry method and in vivo samples were analysed using a RP-HPLC method developed by the author. A deconvolution based Level A model was attempted through a correlation of the percent in vivo input obtained through deconvolution and the percent in vitro dissolution obtained experimentally. A good correlation between the percentages dissolved vs absorbed (R 2 = 0.978) was obtained using level A correlation. Evaluation of the internal predictability of level A correlation was calculated in terms of the percent prediction error, which was found to be below 15%. In a nutshell, the success of the present study warrants further studies in patient volunteers to assess the ability of the MHOP to provide an effective therapy for depression. Copyright © 2013 John Wiley & Sons, Ltd. Key words: milnacipran HCl; osmotic pump; in vivo–in vitro correlation; extended release; protraction index Introduction Oral controlled release (CR) systems are the most popular drug delivery systems. Conventional oral drug delivery systems provide an uncontrolled release of a drug, which may expose the entire dose of the drug at the target site. Therefore, modulation of drug release is required [1]. Fabrication of oral controlled release delivery systems for highly water soluble drugs is the biggest challenge for formulation scientists [2]. Most of the highly water-soluble drugs readily release the drug at a faster rate and produce a toxic concentration of the drug on oral administration if it is not efficiently incorporated into a dosage form [3]. Generally, the formulation scientists’ focus is to achieve a zero order rate of release, which is the desired pattern for extended release formulations of highly water soluble drugs to provide appropriate drug expo- sure for a prolonged period [4]. The majority of per-oral CR dosage forms of water soluble drugs fall into the category of matrix, reservoir or osmotic systems. Generally, drug release from matrix and reservoir systems is affected by pH, hydrodynamic conditions and *Correspondence to: Department of Pharmaceutics, K. B. Institute of Pharmaceutical Education and Research, Sec-23, GH-6, Gandhinagar, Gujarat, India 382023. E-mail: punit_pharma@yahoo.co.in BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. 34: 227–235 (2013) Published online 11 April 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/bdd.1840 Received 4 October 2012 Revised 19 February 2013 Accepted 28 February 2013 Copyright © 2013 John Wiley & Sons, Ltd.