FORMULATION OF SUSTAINED RELEASE CORE AND COAT TABLETS OF LOVASTATIN AND OLEANOLIC ACID: AN IN VITRO AND IN VIVO ANALYSIS

SATISH V. MANDAVE; NARENDRA KUMAR PANDEY; SACHIN KUMAR SINGH; BIMLESH KUMAR; SAURABH SINGH; DILEEP SINGH BAGHEL

doi:10.22159/ajpcr.2025v18i4.54038

Authors

SATISH V. MANDAVE Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India https://orcid.org/0009-0000-4435-1302
NARENDRA KUMAR PANDEY Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India https://orcid.org/0000-0003-0821-7653
SACHIN KUMAR SINGH Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
BIMLESH KUMAR Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India https://orcid.org/0000-0001-8072-5172
SAURABH SINGH Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India https://orcid.org/0000-0002-8474-6007
DILEEP SINGH BAGHEL Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India https://orcid.org/0000-0002-5370-3741

DOI:

https://doi.org/10.22159/ajpcr.2025v18i4.54038

Keywords:

Core and coat, Oleanolic acid, Lovastatin, HPMC, Croscarmellose sodium

Abstract

Objectives: This research aimed to develop core and coat tablets to enhance the therapeutic efficacy of antilipidemic drugs for treating high cholesterol and triglyceride levels in the blood.

Methods: The core and coat tablets were formulated using a combination of two antilipidemic drugs: Lovastatin (LV) and oleanolic acid (OA). LV was incorporated into an immediate-release (IR) layer with various superdisintegrants, while OA formulated into extended-release layer with hydroxypropyl methylcellulose K100.

Results: The core and coat tablets were evaluated for the release profiles of both layers, and excipients were optimized. The IR layer of LV achieved complete release within 60 min, while the release of OA was sustained for up to 12 h. Among the formulations tested, LV9 (95.23%) for immediate release, and OA1 (97.13%) for sustained release, were found to be most suitable when scaled at the desired drug release up to 30 min and 12 h, respectively. Stability studies demonstrated that the optimized formulation remained stable without any degradation for 6 months. Pharmacokinetic and pharmacodynamic studies conducted in rabbit models examined the effects of LV/OA tablets on lipid profiles and body weight. Obesity was induced in the rabbits through a high-fat diet.

Conclusion: The core and coat LV/OA tablets demonstrated significant efficacy in reducing lipid levels and mitigating weight gain compared to the control group.

Downloads

Download data is not yet available.

References

Janani B, Saibaba G, Archunan G, Vidhya K, Karunyadevi J, Angayarkanni J. Purification and cytotoxicity study of lovastatin from soil fungi. Asian J Pharm Clin Res. 2017;10(10):258-62.

Shattat GF. A review article on hyperlipidemia: Types, treatments and new drug targets. Biomed Pharmacol J. 2014;7(2):399-409.

Sharannavar BR, Gadad AP. Transbuccal delivery of spray dried lovastatin from mucoadhesive buccal patches and in vitro characterization. Int J Appl Pharm. 2019;11(5):181-7.

Radha K V., Lakshmanan D. A review: Lovastatin production and applications. Asian J Pharm Clin Res. 2013;6(3):21-6.

Lin C, Wen X, Sun H. Oleanolic acid derivatives for pharmaceutical use: A patent review. Expert Opin Ther Pat. 2016;26(6):643-55. doi: 10.1080/13543776.2016.1182988

Sultana N, Ata A. Oleanolic acid and related derivatives as medicinally important compounds. J Enzyme Inhib Med Chem. 2008;23(6):739-56.

Chang TY, Li BL, Chang CC, Urano Y. Acyl-coenzyme A: Cholesterol acyltransferases. Am J Physiol Endocrinol Metab. 2009;297(1):1-9.

Ayeleso TB, Matumba MG, Mukwevho E. Oleanolic acid and its derivatives: Biological activities and therapeutic potential in chronic diseases. Molecules. 2017;22(11):1915.

Farnier M, Zeller M, Masson D, Cottin Y. Triglycerides and risk of atherosclerotic cardiovascular disease: An update. Arch Cardiovasc Dis. 2021;114(2):132-9. doi: 10.1016/j.acvd.2020.11.006

Somova LO, Nadar A, Rammanan P, Shode FO. Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. Phytomedicine. 2003;10(2-3):115-21.

Tang Y, Teng H, Shi Y, He H, Zhang Y, Yin T, et al. Tablets of paliperidone using compression-coated technology for controlled ascending release. Asian J Pharm Sci. 2018;13(2):143-54. doi: 10.1016/j.ajps.2017.09.005

Gaikwad SS, Kshirsagar SJ. Review on tablet in tablet techniques. Beni Suef Univ J Basic Appl Sci. 2020;9(1):1-7.

Maity S, Sa B. Compression-coated tablet for colon targeting: Impact of coating and core materials on drug release. AAPS PharmSciTech. 2016;17(2):504-15.

Shankar KR, Aminabee S, Lakshmi KC, Reddy GR, Shaik R, Tiyagura V, et al. Effect of various sustained release polymers on floating tablets of carvedilol phosphate-A comparative study. Int J Appl Pharm. 2023;15(6):125-31.

Bajpai M, Singh DC, Bhattacharya A, Singh A. Design and in vitro evaluation of compression-coated pulsatile release tablets of losartan potassium. Indian J Pharm Sci. 2012;74(2):101-6.

Esim O, Hascicek C. Preparation and evaluation of compression-coated

tablets for chronopharmaceutical drug delivery. Ankara Univ Eczac Fak Derg. 2023;47(2):508-19.

Neeharika MS, Jyothi BJ. Preparation and evaluation of zafirlukast compression coated tablets for chronotherapeutic drug delivery. J Pharm Res Int. 2021;33:154-66.

Rane AB, Gattani SG, Kadam VD, Tekade AR. Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers. Chem Pharm Bull (Tokyo). 2009;57(11):1213-7.

Kar A, Ahmed AB. Enhancement of solubility and dissolution of ibuprofen by solid dispersion technique and formulation of sustained release tablets containing the optimised batch of solid dispersion. Int J Curr Pharm Res. 2017;9(5):37-44.

Raza A, Shen N, Li J, Chen Y, Wang JY. Formulation of zein based compression coated floating tablets for enhanced gastric retention and tunable drug release. Eur J Pharm Sci. 2019;132(1):163-73. doi: 10.1016/j.ejps.2019.01.025

Sushma M, Pavani S. Development and evaluation of a novel time and PH-dependent colon targeted drug delivery of ornidazole. Asian J Pharm Clin Res. 2021;14(6):108-11.

Sawada T, Kondo H, Nakashima H, Sako K, Hayashi M. Time-release compression-coated core tablet containing nifedipine for chronopharmacotherapy. Int J Pharm. 2004;280(1-2):103-11.

Gangane PS, Mahajan NM, Danao KR, Pawde GN. Formulation and evaluation of chronomodulated pulsatile therapeutic system for early morning surge in blood pressure. Int J Pharm Pharm Sci. 2015;7(6):337-41.

Remuñán C, Bretal MJ, Núñez A, Vila Jato J. Accelerated stability study of sustained-release nifedipine tablets prepared with gelucire. Int J Pharm. 1992;80(1-3):151-9.

Anil KV, Rada SK. QBD approach in the enhancement of oral bioavailability telmisartan fast dissolving tablets employing starch humate as a new superdisintegrant. Int J Appl Pharm. 2025;17(2):468-482.

Elsayed MM, Aboelez MO, Mohamed MS, Mahmoud RA, El- Shenawy AA, Mahmoud EA, et al. Tailoring of rosuvastatin calcium and atenolol bilayer tablets for the management of hyperlipidemia associated with hypertension: A preclinical study. Pharmaceutics. 2022;14(8):1629.

Katnapally PK, Janaki A, Narsimha R, Anreddy RN, Yellu NR. Pharmacokinetics and pharmacodynamics of atorvastatin alone and in combination with lercanidipine in hyperlipidemic rats. J Pharm Res. 2015;2:66-70.