PREPARATION AND EVALUATION OF MARAVIROC MUCOADHESIVE MICROSPHERES FOR GASTRO RETENTIVE DRUG DELIVERY Original Article SELLAPPAN VELMURUGAN a, b* , MOHAMED ASHRAF ALI a a Department of Pharmaceutics, Sunrise University, Alwar, Rajasthan, India, b Department of Pharmaceutics, KLR Pharmacy College, Paloncha, Telangana, India. Email: willard_cbe@rediffmail.com Received: 11 Feb 2015 Revised and Accepted: 05 Mar 2015 ABSTRACT Objective: The objective of this research was to formulate and evaluate pectin and HPMC different grades mucoadhesive microspheres in combination with sodium alginate for controlled release of maraviroc. Methods: The maraviroc mucoadhesive microspheres was successfully developed by Ionotropic gelation technique, using sodium alginate, pectin, HPMC K4, K15, and K100 as mucoadhesive polymer in various proportions in combination. Further, the prepared maraviroc mucoadhesive microspheres were characterized for particle size, morphology, micrometric studies, entrapment efficiency, mucoadhesion, in vitro drug release, release kinetics, compatibility studies (FTIR) and stability studies. Results: The maraviroc Microspheres was discrete and free-flowing. The mean particle size ranged from 646.3±10.2 μm to 910.0±6.56 μm and the entrapment efficiency ranged from 50.80% to 91.43%. Entrapment efficiency of maraviroc microspheres was increased by increasing drug to mucoadhesive polymer ratio. Scanning electron microscopy revealed the rough surface morphology and no visible cracks of best formulation F16. The FTIR study confirmed the stable nature of maraviroc in the drug-loaded mucoadhesive microspheres. All the maraviroc microspheres showed good mucoadhesive property ranging from 04-73 % in the in-vitro wash off test after 8 hours. The Crystallinity of maraviroc was found to be reduced in prepared mucoadhesive microspheres, which were confirmed by XRD studies. The mechanism of maraviroc release from the mucoadhesive microsphere was found to be anomalous and super case-II transport type. Stability studies were carried out for the best formulation F16 indicates that there is no change in entrapment efficiency and percentage mucoadhesion of the formulation. Conclusion: The results obtained in this research work clearly indicated a promising potential of control release maraviroc mucoadhesive microspheres containing HPMC K100 as a rate controlling polymer for the effective treatment of AIDS/HIV patients. Keywords: Pectin, HPMC K4, HPMC K15M, HPMC K100, Maraviroc, Mucoadhesive microspheres. INTRODUCTION Oral controlled drug delivery systems continue to be the most accepted and popular one among all the drug delivery systems as it offers several advantages over the conventional drug delivery systems like; Improving patient’s compliance and convenience due to reduction of frequency of administration [1]. The problem commonly encountered with the controlled release delivery system is the inability to restrain and localize the dosage form at the gastrointestinal tract, due to the rapid gastrointestinal transit phenomenon [2]. In order to overcome this limitation, it has been proposed, to coupling the bioactives to microparticulate systems an important part of novel drug delivery [3]. However, the success of microparticulate carrier system is limited due to their limited residence time at the site of absorption [4]. It can be executed by coupling mucoadhesion characteristics to microparticulate by using mucoadhesive polymers and developing mucoadhesive microspheres [5]. Mucoadhesive microspheres have advantages like efficient absorption and improved bioavailability of the bioactives due to high surface to volume ratio, an intimate contact with the mucus membrane and drug targeting to the absorption site [6]. Maraviroc is a new class of anti HIV drug known as CCR5 antagonists and only oral entry inhibitor approved for the treatment of HIV 1inf ection [7]. Maraviroc poorly absorbed from lower gastrointestinal tract and the oral bioavailability after a single 300-mg oral dose is reported to be 33% with biological half life of 10.6±2.7 h. Administration of conventional dosage form suffers from certain drawbacks like first pass metabolism, variation of absorption and fluctuation in the plasma drug level [8]. In our previous investigation [9], sodium alginate mucoadhesive microspheres of maraviroc controlled the drug release for 8 hrs. To prolong the maraviroc release, improve mucoadhesion, bioavailability and to reduce dosing frequency, a suitable formulation was required with a controlled rate to treat anti HIV patients. In the present study, mucoadhesive microspheres were developed using a hydrophilic polymer, Hydroxypropyl methylcellulose (HPMC K4M, K15M and K100) and pectin in combination with sodium alginate. MATERIALS AND METHODS Materials Maraviroc was a gift sample from Hetro Pharma Ltd, Hyderabad. Sodium alginate, HPMC different grades, pectin polymers were received as the gift sample from Cadila Pharma, Ahmedabad, India. All other ingredients used were of analytical grade. Formulation of Maraviroc mucoadhesive microspheres The Maraviroc mucoadhesive microspheres were prepared by Ionotropic external gelation technique [10, 11], the composition of various formulations was mentioned in Table1. Maraviroc and mucoadhesive polymers were individually passed through sieve number 60. The required quantities of mucoadhesive polymers were dissolved in purified water to form a homogenous polymer solution. Maraviroc was added to the polymer solution and mixed thoroughly with stirrer at 400 rpm to form a homogeneous dispersion. The resulting homogeneous dispersion was sonicated for 30 min to remove any air bubbles. For the formation of microspheres the dispersion was then extruded manually drop wise into aluminum sulphate solution (10%) using a polyethylene syringe (needle size 24 G). The extruded droplets were retained in the aluminium sulphate solution for 30 min to complete the curing reaction and to produce spherical rigid maraviroc microspheres [9]. The obtained microspheres were collected by decantation, washed repeatedly with distilled water to remove excess aluminum impurity and dried at 45 °C for12 h. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 5, 2015 Innovare Academic Sciences