Co-Milling: A Successful Approach to Enhance Solubility of a Poorly Soluble Antihypertensive Drug
The aim of the work was to enhance the solubilization of Olmesartan-medoxomil (OM) and formulate stable, rapidly-dissolving-tablet formulations. OM, on the other hand, is classified as Biopharmaceutics Classification System (BCS) Class II drug, which indicates that it is characterized by water-insolubility. Therefore, increasing its solubilization has the potential to boost its bioavailability. For the OM evaluation, a new HPLC technique was invented and then validated in accordance with international standards. The formulation of tablets involved co-milling with certain superdisintegrants, specifically croscarmellose sodium (Ac-Di-Sol) and crospovidone in varying percentages, followed by mixing with pH-adjusting substances such as calcium carbonate to increase solubilization in cases where the drug is soluble in alkaline. Following the evaluation of the created formulations, the optimized formulations were selected for further stability assessment. Co-milling process with crospovidone greatly improved the olmesartan release. The optimized formulations were OD11 and OD12, which exhibited fast disintegration, and the release exceeded 90% within 10 min, while the release for Olmesartan medoxomil pure standard was 9.8% after 10 min. The OD11 and OD12 were chosen for further stability assessment and revealed good stability behavior, as the study on optimized formulations revealed that the degradation was less than 5% after storage for six months at 40 °C and 75% relative humidity. Some formulations exhibited good results in terms of disintegration and release. The results of the formulations (OD11 and OD12) suggested that co-grinding with crospovidone may increase the solubilization of OM to greater than 90% after 10 minutes.
Alan, S., Yu, L. & BChir, M.B. in Brenner and Rector's The Kidney, 2020
Al-Shdefat, R. (2020). Solubility determination and solution thermodynamics of olmesartan medoxomil in (PEG-400 + water) cosolvent mixtures. Drug Dev Ind Pharm., 46 (12), 2098-2104. https://doi.org/10.1080/03639045.2020.1847136
Arun, B., Narendar, D. & Veerabrahma K. (2018). Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation, Artificial Cells, Nanomedicine, and Biotechnology, 46(1), 126-137. https://doi.org/10.1080/21691401.2017.1299160
Bayoumi, A.A. (2018). Enhancement of Solubility of A Poorly Soluble Antiplatelet Aggregation Drug by Cogrinding Technique. Asian J Pharm Clin. Res, 11, 340-344. https://doi.org/10.22159/ajpcr.2018.v11i10.27136
Choursiya, A. & Pandit, D. (2021). Formulation and Evaluation of Fast Dissolving Tablets of Lansoprazole by Solubility Enhancement Technique. Current Research in Pharmaceutical Sciences, 11(2), 54-64. https://doi.org/10.24092/CRPS.2021.110203
Dhakal, B., Thakur, J.K., Mahato, R.K., Rawat, I., Rabin, D.C. & Chhetri, R.R., et al. (2022). Formulation of Ebastine Fast-Disintegrating Tablet Using Coprocessed Superdisintegrants and Evaluation of Quality Control Parameters. Scientific World Journal. 19, 9618344. https://doi.org/10.1155/2022/9618344
FDA (November, 2014) Expiration Dating and Stability Testing for Human Drug Products. Retrieved on April 4, 2022 from https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/expiration-dating-and-stability-testing-human-drug-products
González, R., Peña, M.Á. & Torrado, G. (2022). Formulation and Evaluation of Olmesartan Medoxomil Tablets. Compounds, 2 (4), 334-352. https://doi.org/10.3390/compounds2040028
Hari, K., Rajeswari, S. & Ramanamurthy, V.K. (2018). Preparation and Evaluation of Orally Disintegrating Tablets of Drotaverine Hydrochloride Using Sublimation Technique. Int J Pharm Pharm Sci, 10, 85-95. https://doi.org/10.22159/ijpps.2018v10i5.24503
ICH. International Conference on Harmonization, Validation of Analytical Procedures: Text and Methodology, Q 2 (R1). ICH, 2005.
ICH Q1A (R2) Stability testing of new drug substances and drug products - Scientific guideline (2003)
Karuna, D.S., Sowjanya, L., Ubaidulla, U., Rathnam, G. (2014). Formulation and Evaluation of Triple Drug Combination of Olmesartan Medoximal, Amlodipine Besylate and Hydrochlorothiazide Tablets, International Journal of Advanced Pharmaceutics, 4(2),146-153.
Kassem, A.M., Mohamed, I.M. & Mohamed, A.A. (2016). Development and validation of a stability indicating assay for azilsartan kamedoxomil in solid dosage forms. Int. J. of Adv. Res, 4, 1630-1639. https://doi.org/10.21474/IJAR01/1973
Koike, H., Konse, T., Sada, T., Ikeda, T., Hyogo, A., Hinman, D., Saito, H. & Yanagisawa, H. (2003). Annual Report Sankyo Research Laboratories, 55: 1-91.
Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press (2011).
Rahane, R.D. & Rachh, P. (2018). A review on fast dissolving tablet. Journal of Drug Delivery and Therapeutics. 8, 50-55. https://doi.org/10.22270/jddt.v8i5.1888
Rahi, F.A., Mohammed, M.S & Fayyadh, M.S. (2021). Linagliptin and gliclazide di-loaded extended-release nanoparticles: formulation and evaluation. Wiad Lek, 74 (9 cz 2):2315-2322. https://doi.org/10.36740/WLek202109212
Hidayati, N., Sulaiman, T & Nurhaini, R. (2020). Optimization formula of fast disintegrating tablets Ketoprofen β-cyclodextrin inclusion complex with sodium starch glycolate and crospovidone as the superdisintegrants. J Phys Conf Ser. 1517, 012047. https://doi.org/10.1088/1742-6596/1517/1/012047
Huang, Y., Cao, L., Parakhonskiy, B.V. & Skirtach, A.G. (2022). Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications. Pharmaceutics, 14, 909. https://doi.org/10.3390/pharmaceutics14050909
Saab, M. & Mehanna, M.M. (2019). Disintegration time of orally dissolving films: various methodologies and in-vitro/in-vivo correlation. Pharmazie, 74(4), 227-230. https://doi.org/10.1691/ph.2019.8231
Sumaiyah, S., Mentari, J. & Suryanto S. (2019). The Effect of Crospovidone on the Dissolution Profile of Amlodipine Besylate from Fast Orally Dissolving Film. Open Access Maced J Med Sci., 7, 3811-3815. https://doi.org/10.3889/oamjms.2019.510.
The Pharmacopoeia of United States of America", 43th Ed., National Formulary 38, Mack publishing Co. Easton, vol. 2, Electronic version (2019).
World Health Organization (1996) Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms. Retrieved on April 4, 2022 from https://www.paho.org/hq/dmdocuments/2008/6_Annex_5_report_34.pdf
Vaughan, A.S., Coronado, F., Casper, M., Loustalot, F. & Wright, J.S. (2022). County-Level Trends in Hypertension-Related Cardiovascular Disease Mortality-United States, 2000 to 2019external icon. J Am Heart Assoc, 11(7), e024785. https://doi.org/10.1161/jaha.121.024785