VOL 33 (4) 2022: 666–679 | RESEARCH ARTICLE 666 Indonesian Journal of Pharmacy Indonesian J Pharm 33(4), 2022, 666-679 | journal.ugm.ac.id/v3/IJP Copyright © 2022 by Indonesian Journal of Pharmacy (IJP). The open access articles are distributed under the terms and conditions of Creative Commons Attribution 2.0 Generic License (https://creativecommons.org/licenses/by/2.0/). Favourable Drug-Lead Pharmacokinetic Features for Designing Gallic Acid-Standardized Syzygium Polyanthum Aqueous Extract-Based Product Hassan Fahmi Ismail 1 , Anis Fadhlina 2 , Siti Nurazwa Zainol 3 , Archan Kumar Mamillapalli 4 , Vijayabalaji Venkatesan 4 , Rajesh Eswarappa 4 , Renuka Pillai 4 and Fadzilah Adibah Abdul Majid 1 * 1. Institute of Marine Biotechnology, 21030 Universiti Malaysia Terengganu, Malaysia. 2. Institute of Food Security and Sustainable Agriculture, Universiti Malaysia Kelantan, 17600 Jeli, Kelantan. 3. Proliv Life Sciences Sdn Bhd, D-1-15, Residensi Bistaria, Jln Ulu Kelang, Taman Ukay Bistari, 68000 Ampang, Selangor Darul Ehsan, Malaysia 4. Aurigene Pharmaceutical Services Limited, Bollaram Road, Miyapur, Hyderabad-500 049, Telangana, India. ABSTRACT Submitted: 17-12-2021 Revised: 20-06-2022 Accepted: 02-12-2022 *Corresponding author SettingsFadzilah Adibah Abdul Majid Email: f.adibah@umt.edu.my In this study, Syzygium polyanthum was standardized against gallic acid (GA), and a complete pharmacokinetic test was conducted using in vitro and in vivo models against this phytochemical. High-performance liquid chromatography showed that GA is a major phytochemical in aqueous extract of S. polyanthum. It exhibited a low equilibrium solubility and physiochemical stability at pH 2.0 and 7.4, but it deteriorated rapidly at pH 9.2. It showed low permeability toward Caco-2 intestinal absorption with eight times slower absorption in oral than intravenous administration. GA was unstable in mouse, rat, and dog plasma sera with in vitro half-lives (t1/2) of 60, 53, and 56 min, respectively, but was relatively stable in human plasma serum (t1/2 = 185 min). Approximately 5.6% of GA (10 µM) bound to the human plasma proteins. GA was stable in mouse, rat, dog, and human microsomal extracts with in vitro microsomal intrinsic clearance values of 72, 68, 6, and 22 µL/min/mg, respectively. GA selectively inhibited or stimulated the activity of the tested CYP450 enzymes. The in vivo oral bioavailability of GA was 54%, with short elimination half-life and a high volume of distribution. Thus, the mention pharmacokinetic features of GA must be considered during the development of GA-based products to yield the optimum dosage and pharmacological effect. Keywords: Gallic acid, Syzygium polyanthum, aqueous extract, pharmacokinetic. INTRODUCTION Syzygium polyanthum or Eugenia polyantha is distributed in Malaysia, India, Vietnam, Indonesia, Thailand, and Singapore. In Malaysia, it has a common name of “Salam.” It has been traditionally used as remedies for various types of illnesses. The leaves of this plant are traditionally used for treating itchy skin, abdominal pain, high blood pressure, diabetes, and gastritis. In Indonesia and India, the leaves of this plant can be used as an ingredient in curry and soups and can even be eaten raw. Roots and fruits of S. polyanthum are traditionally used to counteract hangover symptoms (Lelono et al., 2009; Sumono & Sd, 2008; Grosvenor et al., 1995; Ismail & Ahmad, 2019). These traditional claims were scientifically justified through numerous studies on the leaves, fruits, roots, stem, and barks of S. polyanthum. Many studies focused on the leaves because of their numerous bioactivities, such as antimicrobial (Kusuma et al., 2011; Hamad et al., 2017; Grosvenor et al., 1995; Fitri, et al., 2017; Mohamed et al., 1996), antioxidant (Kusuma et al., 2011; Wong, et al., 2006; Perumal et al., 2012; Har & Intan, 2012; Darusman et al., 2013; Othman et al., 2014; Safriani, et al., 2015; Widyawati et al., 2016; Hidayati et al., 2017), antihypertensive (Ismail et al., 2013; Ismail & Ahmad, 2017; Ismail et al., 2018), antidiarrheal