FORMULATION, EVALUATION, AND IN VIVO ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF MORINGA GRANULES Original Article HARITH JAMEEL MAHDI ALSAMMARRAIE 1* , NURZALINA ABDUL KARIM KHAN 2 , ROZIAHANIM MAHMUD 3 *1 Department of Applied Chemistry, Faculty of Applied Sciences, University of Samarra, Iraq, 2 Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, USM, Malaysia, 3 Received: 12 Dec 2020, Revised and Accepted: 17 Feb 2021 Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, USM, Penang, Malaysia Email: ph.harith75@gmail.com ABSTRACT Objective: Consumption of crude natural products like plants and herbs for mitigation or treatment of illnesses usually accompanied with inconsistent therapeutic effects because of poor solubility and low bioavailability of active phytochemical(s) in addition to product instability. To overcome all of above mentioned drawback ethanol extract of Moringa oleifera leaf was formulated as standardised solid dosage form. Methods: Different types of materials as an adsorbent, surfactant and other necessary excipients were tested to be use in formulation of Moringa granules utilising wet granulation method. The formulated Moringa granules was then evaluated for organoleptic properties and physical characteristics, in vitro dissolution test, compatibility, drug content, heavy metal tests and microbial limit tests. Additionally, the in vivo anti- inflammatory against Carrageenan-induced paw oedema and anti-arthritic activity against CFA-induced arthritis were also assessed. Results: 95% ethanol extract of M. oleifera leaves was successfully formulated as standardised granules for oral administration utilising simple and low- cost techniques. Dissolution rate for the marker compounds was increased by an average of 1.076 fold. Animal groups given the prepared Moringa granules showed an improvement in the anti-inflammatory activity and the anti-arthritic activity compared to animal groups given crude extract at the same dose level. Additionally, all the treatment groups showed a significant difference at P<0.05 and P<0.01 compared to control group. Conclusion: To the best of our knowledge, this work was the first to use gum Arabic in the formulation of a standardised botanical pharmaceutical dosage form of M. oleifera crude extract. Additionally, formulation of Moringa granules apparently improves the drug release profile and bioactivity compare to Crude Moringa extract. Keywords: Moringa oleifera, Moringa granules, Organoleptic properties, Anti-inflammatory, Anti-arthritic © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021v13i3.40478. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION The interest in botanical products has been regenerated because of the discovery of many novel natural bioactive phytochemicals [1]. However, the therapeutic potential of these compounds is often limited by their poor solubility, low bioavailability and product instability [2]. In this regard, pharmaceutical scientists should explore delivery systems that can enhance drug solubility and bioavailability and improve product stability. The complexity of phytoconstituents and the indecision about the phytochemical(s) responsible for bioactivity are the most challenging problems in formulation and evaluation of herbal products. Moringa oleifera Lam is well-known and most widely cultivated species of Moringaceae, which is a mono-generic flowering plant family that comprises 13 species. M. oleifera has been founded in many tropic and sub-tropic regions worldwide. The plant is referred to by a number of names such as horseradish tree, drumstick tree, ben oil tree, miracle tree, and “Mother’s Best Friend”. The leaf of M. oleifera is the most valuable part of the plant used as food and traditional medicine source. Large number of nutrients as such proteins, minerals and fibres that affords an important role in the human diet as well as it is a valuable nutritive, healing and socioeconomic potentials [3]. An online survey indicates a large number of M. oleifera medicinal and dietary supplement products, alone or in herbal combinations, available in the global markets. The products are mostly in oral dosage form as tablets, capsules, tea bags, elixir, syrup and leaf powder for decoction. Our survey and that conducted by [4] revealed that almost all of the reviewed products shared one or more features of the following variable in product composition, not standardised against a bioactive phytochemical marker(s) and inconsistence in medicinal indications and uses despite originating from the same plant part and using the same dose strength and same manufacturing processes. In this study, an ethanol extract of M. oleifera leaves had been formulated as a standardised granules, evaluated for their organoleptic properties, physical and chemical characteristics, and subjected to in vitro dissolution test. Additionally, in vivo bioactivity of the formulated granules as anti-arthritis and anti- nociceptive were also evaluated. To the best of our knowledge, this the first time that ethanol extract of Moringa oleifera leaves was formulated as a solid dosage form with standardised content of marker compounds, standardised drug release rate and improved bioactivity. MATERIALS AND METHODS Chemicals and reagents Astragalin (Kaempferol-3-O-glucoside) 98% purity, Extrasynthese (Genay, France); Cryptochlorogenic acid (4-O-Caffeoylquinic acid) 98% purity, Chemfaces (Wuhan, China); Ethanol 95%, Fisher Scientific (Selangor, Malaysia). λ-Carrageenan, Indomethacin, Complete Freund’s Adjuvant (CFA) (1 mg/ml) of heat killed dried M. tuberculosis (strain H37Ra, ATCC 25177) suspended in 1.5 ml mannide monooleate and 8.5 ml, and Tween (Polysorbate) 20, 40, and 80all purchased from Sigma-Aldrich, St., MO, USA. Gum Arabic and HPMC, Methocel K100M CR were purchased from Colorcon Ltd, New Hampshire, USA. Magnesium stearate, RandM Marketing, Essex, UK; Microcrystalline cellulose (Avicel PH200) 200, FMC BioPolymer, Newark DE, USA. Equipment and instruments BUCHI R-114 rotary vacuum evaporator, BUCHI Labortechnik AG (Flawil, Switzerland); Drying oven, Memmert GmbH and Co. (Schwabach, Germany); Shimadzu HPLC system, Shimadzu Corporation (Kyoto, Japan); Digital micrometer, Mitutoyo, ID- C1012EXBS, Kawasaki, Japan; Electrolab ETD-1020 Tap Density International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Issue 3, 2021