EVALUATION OF ANTIULCER ACTIVITY OF MUCOADHESIVE MICROGRANULES CONTAINING RANITIDINE HYDROCHLORIDE IN EXPERIMENTAL RATS Original Article ENDANG DIYAH IKASARI 1* , ANANG BUDI UTOMO 1 , ANASTASIA SETYOPUSPITO 1 , DHIMAS ADHITYAASMARA 1 , HANNY SETYOWATI 2 1 Yayasan Pharmasi College of Pharmacy, Semarang, Indonesia, 2 Received: 21 Sep 2016, Revised and Accepted: 15 Nov 2016 Reseach and Development Department, Borobudur Natural Industry, Semarang, Indonesia Email: eri_ung@yahoo.co.id ABSTRACT Objective: Ranitidine hydrochloride is a competitive inhibitor of histamine H2-receptors, the drug of choice in the treatment of ulcer. The drug has a short biological half-life of approximately 2–3 h, thus a sustained release dosage form of ranitidine HCl is desirable. The aim of this study was to formulate and in vitro evaluate micro granules of ranitidine HCl using 8% aloe vera powder due to cytoprotective effects. Methods: Micro granules were prepared by wet granulation method using aloe vera powder as bio-adhesive polymer. The animals were albino male Wistar rats, divided into 4 groups. One group as a control group, the second group as placebo, third groups received ranitidine without aloe vera, and fourth groups as the treated group received ranitidine micro granules. The damage of ulceration was induced with absolute ethanol, dosing at 1 ml/200 g animal body weight. The microscopic observation was done at the first and third day after treatment. Results: At the first day, the reference and treated group showed the lower ulcer number score mean and ulcer diameter score mean than placebo group. The ulcer index and curative value of reference group were better than treated group, 51.3% and 29.7% respectively. But, at the third day, ulcer index and curative value of treated group possessed better result than reference group, confirming that aloe vera acts as mucoadhesive polymer and gives the release of drug in a sustained manner. Conclusion: Aloe vera powder (Aloe vera (L.) Webb) can be used to formulate micro granules for the prolonged delivery of ranitidine HCl. The micro granules containing in ranitidine dose of 0,04 mg/kg body weight reduce the ulceration induced by absolute ethanol Keywords: Aloe vera powder, Microgranules, Ranitidine HCl, Ulceration, Macroscopic view © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: INTRODUCTION Ranitidine hydrochloride is a competitive inhibitor of histamine H2- receptors, drug of choice in the treatment of duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), and erosive esophagitis [1]. The recommended adult oral dosage of ranitidine is 150 mg twice daily or 300 mg once daily. A conventional dose of 150 mg can inhibit gastric acid secretion up to 5 h but not up to 10 h. An alternative dose of 300 mg leads to plasma fluctuations; thus a sustained release dosage form of ranitidine HCl is desirable [2]. There are a number of approaches that can be used to prolong gastric retention time, one of them is polymeric bioadhesive systems. Studied by Maru and Singh [3], aloe vera gel can act as natural polymer bioadhesive in many biomedical applications, including drug delivery systems because of their polysaccharide contents. This substance can be found in the parenchymal tissues of Aloe vera [4]. Therefore, the objective of this study is to examine the influence of 8% of aloe vera powder applied as mucoadhesive agent containing in ranitidine micro granules. MATERIALS AND METHODS The materials http://dx.doi.org/10.22159/ijcpr.2017v9i1.16605 The materials used were Aloe vera (Aloe vera (L.) Webb) powder, aqua destilata, FDC green, ethanol 96% (technical grade), sodium chloride (technical grade), ranitidine hydrochloride (pharmaceutical grade), polyvinylpyrrolidone K-30 (pharmaceutical grade), lactose (pharmaceutical grade), carbopol 934 P (pharmaceutical grade), acid hydrochloride (analytical grade), formaldehyde (analytical grade), ethanol absolute (analytical grade). The instruments The instruments used were an oven (Binder), tray, mixer, ceramic mortar, sieve no. 60 mesh, drying apparatus, pH meter (Hanna instrument), moisture content (G-Won Hitect Co. LDT, RRC), stopwatch, spectrophotometer UV-Vis mini 1240 (Shimadzu), dissolution apparatus type I basket (Veego VDA 6-DR), freeze dryer, water restraint, oral injection spuit, glass apparatus, surgical apparatus, analytical scales, and digital camera. Preparation of Aloe vera powder Aloe vera (Aloe vera (L.) Webb) which has been identified were washed, then cutted, and peeled. The aloe vera was heated by water (at a temperature of 70 °C for 10 min) to get al. oe vera gel. The gel was filtered and blended into aloe vera pulp, then dried using freeze dryer (at a temperature of 0 °C and pressure of 4.58 torr) by adding dextrin 15%. Next, the obtained dried powder was sieved through the sieve no 60 mesh. The characteristics were tight, white- brownish, odourless, tasteless, and loose powder [5]. From 6.6872 kg aloe vera pulp was obtained 436 grammes of aloe vera powder. Therefore the yield was 6.52%. Formulation of micro granules containing with ranitidine HCl Micro granules were prepared in a ceramic mortar by the modified wet granulation technique. Ranitidine HCl, 8% aloe vera powder, Carbopol 934P, PVP K-30, FDC green, and lactose were weighted, then blended and mixed thoroughly. Next, the proper amount of 5% PVP K-30 in ethanol (and FDC green) was gradually added to moisten the powders. The wet granules were sieved no 30 and 40 mesh, then dried (at a temperature of 35 °C for 25 min). The micro granules were compressed to get the tablet form. Both placebo and Ranitidine without aloe vera was used to compare the antiulcer activity test (fig. 1). International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 9, Issue 1, 2017