Novel gastroretentive formulation of an Ayurvedic churna for peptic ulcers: Optimization and evaluation

Year 2024, Volume: 28 Issue: 6, 2251 - 2262, 28.06.2025

Priya Shah , Sheetal Acharya , Kilambi Pundarikakshudu Maitreyi N. Zaveri

https://doi.org/10.29228/jrp.899

Abstract

Avipattikar churna is well known Ayurvedic formulation in India for Amalpitta. Voluminous dose leading to poor patient compliance, less residence time in stomach and less stability are the major limitations of the Churna. Thus, the objective of research work was to develop a novel gastroretentive floating drug delivery system of Avipattikar churna. The churna was prepared and evaluated for phytochemical analysis. The main constituents, Jalap, and Clove, contained scopoletin and eugenol as active markers. A floating tablet of Avipattikar churna was optimized using a 32 factorial design, with HPMC K4M and HPMC K100M concentrations as independent factors and floating lag time (FLT) and % release of scopoletin and eugenol at 1 h, at 4 h and at 8h as dependent variables. The optimized formulations were evaluated by physical parameters. The optimized formulation was selected based on factorial design and numerical desirability Index values. In-vitro dissolution study was performed for optimized formulation and compared with marketed Avipattikar churna. Release mechanisms of markers were determined using various kinetic models and DD solver. The stability studies followed ICH guidelines. The preliminary trial batches were formulated by using direct compression method. 15% of the mixture of HPMC K100M and HPMC K4M was finalised based on the factorial design results and desirability index. Optimized formulation showed FLT of 88 ± 0.3 sec, with cumulative eugenol release at 1h (18.78%), 4h (60.23%), and 8h (95.36%). Scopoletin cumulative release was 21.43%, 68.51%, and 89.34% at 1h, 4h, and 8h, respectively. In a release kinetics, formulation showed diffusion mechanism followed by anomalous diffusion. The formulation was stable as revealed by 3 months accelerated stability studies as per ICH guidelines. From the experiments, 15% of HPMC K100M and HPMC K4M gave shorter floating lag time, good consistency and extended the duration of drug release over time frame of 8h. The formulation was found to be stable.

Keywords

Gastroretentive floating tablet , Avipattikar churna (An Ayurvedic classical formulation) , 32Factorial design , Drug release

References

• [1] Anonymous. The Ayurvedic Pharmacopoeia of India: Ministry of Health and Family Welfare, Department of AYUSH, Government of India, India; 2007.
• [2] Raju D, Ilango K, Chitra V, Ashish K. Evaluation of Anti-ulcer activity of methanolic extract of Terminalia chebula fruits in experimental rats. Int J Pharm Sci Res. 2009;1(3):101.
• [3] Khandare R, Gulecha V, Mahajan M, Mundada A, Gangurde H. Evaluation of antıulcer actıvıty polyherbal formulatıon. Int J Pharm Res Dev.-Online 2009.
• [4] Zaveri M, Patel V. Gastroprotective effects of Polyherbal Ayurvedic Formulation: An Avipattikar churna. Am J PharmTech Res. 2011;1(4):219-231.
• [5] al-Yahya MA, Rafatullah S, Mossa JS, Ageel AM, Parmar NS, Tariq M. Gastroprotective activity of ginger zingiber officinale rosc., in albino rats. Am J Chin Med. 1989;17(1-2):51-56. https://doi.org/10.1142/s0192415x89000097.
• [6] Santin JR, Lemos M, Klein-Júnior LC, Machado ID, Costa P, de Oliveira AP, Tilia C, de Souza JP, de Sousa JP, Bastos JK, de Andrade SF. Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn Schmiedebergs Arch Pharmacol. 2011;383(2):149-158. https://doi.org/10.1007/s00210-010-0582-x
• [7] Sabale VP, Gadge GG. Factorial design approach to fabricate and optimize floating tablets based on combination of natural polymer and rice bran wax. Beni-Suef Univ J Basic Appl Sci. 2022;11(1):1-12. https://doi.org/10.1186/s43088-021-00186-9
• [8] Shinkar DM, Aher PS, Kothawade PD, Maru AD. Formulation and in vitro evaluation of fast dissolving tablet of verapamil hydrochloride. Int J Pharm Sci. 2018;10:93-99. https://doi.org/0.22159/ijpps.2018v10i10.28714
• [9] Reddy PS, Bose PSC, Saritha D, Sruthi V. Formulatıon and evaluatıon of colon targeted matrıx tablet usıng natural tree gums. Int J Pharm Sci. 2018;10(9):92-97. https://doi.org/10.22159/ijpps.2018v10i9.27255
• [10] Makwana A, Sameja K, Parekh H, Pandya Y. Advancements in controlled release gastroretentive drug delivery system: A review. J Drug Deliv Ther. 2012;2(3). https://doi.org/10.22270/jddt.v2i3.164
• [11] Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63(3):235-259. https://doi.org/10.1016/s0168-3659(99)00204-7
• [12] Patel N, Patel V, Yeole P. Studies on formulation and evaluation of ranitidine floating tablets. Indian J Pharm Sci. 2005;67(6):703-709.
• [13] Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opin Drug Deliv. 2006;3(2):217 33. https://doi.org/10.1517/17425247.3.2.217
• [14] Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastroretentive dosage forms. J Control Release. 2003;90(2):143-162. https://doi.org/ 10.1016/s0168-3659(03)00203-7
• [15] Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled-release system for gastric retention. Pharm Res. 1997;14:815-819. https://doi.org/ 10.1023/a:1012171010492
• [16] Ram HA, Lachake P, Kaushik U, Shreedhara C. Formulation and evaluation of floating tablets of liquorice extract. Pharmacognosy Res. 2010;2(5):304. https://doi.org/ 10.4103/0974-8490.72329
• [17] Djebbar M, Chaffai N, Bouchal F. Development of floating tablets of metformin HCl by thermoplastic granulation. Part II: In vitro evaluation of the combined effect of acacia gum/HPMC on Biopharmaceutical performances. Adv Pharm Bull. 2020;10(3):399. https://doi.org/10.34172/apb.2020.048
• [18] Hiremath PS, Saha RN. Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies. Aaps Pharmscitech. 2008;9:1171-1178. https://doi.org/ 10.1208/s12249-008-9159-0
• [19] Vora C, Patadia R, Mittal K, Mashru R. Risk based approach for design and optimization of stomach specific delivery of rifampicin. Int J Pharm. 2013;455(1-2):169-181. https://doi.org/10.1016/j.ijpharm.2013.07.043
• [20] Shah P, Pundarikakshudu K, Patel K, Zaveri M. Simultaneous estimation of eugenol and scopoletin by UV spectroscopic method using in-house Avipattikar churna. J Young Pharm. 2022;15(1):92-97. https://doi.org/ 10.5530/097515050521
• [21] Singh B, Kapil R, Nandi M, Ahuja N. Developing oral drug delivery systems using formulation by design: Vital precepts, retrospect and prospects. Expert Opin Drug Deliv. 2011;8(10):1341-1360. https://doi.org/10.1517/17425247.2011.605120
• [22] Suksaeree J, Monton C, Charoenchai L, Chankana N. Microwave-assisted drying of Prasakanphlu herbal granules and formulation development of Prasakanphlu tablets: Design of Experiments approach. Adv Trad Med. 2023:1-12. https://doi.org/10.1016/j.cep.2021.108726
• [23] Singh B, Kumar R, Ahuja N. Optimizing drug delivery systems using systematic" design of experiments." Part I: fundamental aspects. Crit Rev Ther Drug Carrier Syst. 2005;22(1):27-105. https://doi.org/10.1615/critrevtherdrugcarriersyst.v22.i1.20
• [24] Shah PP, Mashru RC, Rane YM, Thakkar A. Design and optimization of mefloquine hydrochloride microparticles for bitter taste masking. AAPS PharmSciTech. 2008;9:377-389. https://doi.org/ 10.1208/s12249-008-9052-x
• [25] Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. https://doi.org/10.1016/S0928-0987(01)00095-1
• [26] Wagner JG. Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. J Pharm Sci. 1969;58(10):1253-1257. https://doi.org/10.1002/jps.2600581021
• [27] Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25-35. https://doi.org/10.1016/0378-5173(83)90064-9
• [28] Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145-1149. https://doi.org/10.1002/jps.2600521210
• [29] Abdul Rasool BK, Sammour R. DDSolver Software application for quantitative analysis of ın vitro drug release behavior of the gastroretentive floating tablets combined with radiological study in rabbits. Curr Drug Deliv. 2022;19(9):949-965. https://doi.org/ 10.2174/1567201819666220304203014
• [30] EMA ICH Q1A (R2) Stability Testing of New Drug Substances and Products - Scientific Guideline. Available online: ICH Q1A (R2) Stability Testing of New Drug Substances and Drug Products - Scientific Guideline | European Medicines Agency (EMA) (accessed on 29 March 2023).