MICRONIZED EUTECTIC MIXTURE OF FENOFIBRIC ACID-SACCHARIN FORMATION FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT

USWATUL HASANAH; LIZA WAHYUNI; ERIZAL ZAINI

doi:10.22159/ijap.2023.v15s1.47514

Authors

USWATUL HASANAH Department of Pharmaceutics, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatra, 25163, Indonesia
LIZA WAHYUNI Department of Pharmaceutics, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatra, 25163, Indonesia
ERIZAL ZAINI Department of Pharmaceutics, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatra, 25163, Indonesia

DOI:

https://doi.org/10.22159/ijap.2023.v15s1.47514

Keywords:

Dissolution enhancement, Eutectic mixture, Fenofibric acid, Microparticles, Saccharin, Spray drying

Abstract

Objective: This study aims to increase the solubility and dissolution rate of fenofibric acid by forming a micronized eutectic mixture of fenofibric acid-saccharin with spray drying technique.

Methods: Suspension of the eutectic mixture was prepared in ethanol: distilled water (3:1) followed by a spray drying method to obtain the microparticles. Microparticles characterization was performed by particle size analysis (PSA), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), FT-IR spectroscopy, and scanning electron microscopy (SEM). Solubility test was carried out in CO₂-free distilled water, meanwhile the dissolution rate study was conducted in phosphate buffer solution at pH 6.8.

Results: The results showed the mean of the samples’ particle size was 72.29±7.33 µm. Compared to the intact fenofibric acid, the micronized eutectic mixture sample has a decreased melting point, fusion enthalpy, and crystallinity without any wavenumber shifted in the FT-IR spectra. The solubility of micronized eutectic mixture was 2.2 times higher than intact fenofibric acid, while the amount of micronized eutectic mixture dissolved at 60 min was 11.7 times higher.

Conclusion: It can be concluded that the spray-dried micronized eutectic mixture of fenofibric acid-saccharin was having the ability to enhance the dissolution of fenofibric acid.

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References

Sun T, Hall ML, Isbester PK. White heat BR. Fenofibric acid polymorph; methods of making; and methods of use thereof. United states application publication. Vol. 56(4); 2009.

Shukla AK, Bishnoi RS, Dev SK, Khumar M, Fenin V. Biopharmaceutical classification system: tool-based prediction for drug dosage formulation. Adv Pharm J. 2017;2(6):204-10.

Windriyati YN, Sumirtapura YC, Pamudji JS. Comparative in vitro and in vivo evaluation of fenofibric acid as an antihyperlipidemic drug. Turk J Pharm Sci. 2020 Apr 1;17(2):203-10. doi: 10.4274/tjps.galenos.2019.27147, PMID 32454781.

Hens B, Brouwers J, Corsetti M, Augustijns P. Gastrointestinal behavior of nano- and microsized fenofibrate: in vivo evaluation in man and in vitro simulation by assessment of the permeation potential. Eur J Pharm Sci. 2015;77:40-7. doi: 10.1016/j.ejps.2015.05.023.

Anggraini D, Umar S, Arifin H, Zaini E. Dissolution rate enhancement and physicochemical characterization of a fenofibric acid–nicotinamide eutectic mixture. Trop J Nat Prod Res (TJNPR). 2021 Sep 1;5(9):1614-8. doi: 10.26538/tjnpr/v5i9.

Zaini E, Azhari D, Fitriani L. Identification and characterization of solid binary system of quercetin-nicotinamide. Orient J Chem. 2016 Jun 1;32(3):1545-50. doi: 10.13005/ojc/320330.

Saurav A, Kaushik M, Mohiuddin SM. Fenofibric acid for hyperlipidemia. Expert Opin Pharmacother. 2012;13(5):717-22. doi: 10.1517/14656566.2012.658774, PMID 22404421.

Nikalje AP. Nanotechnology and its applications in medicine. Med Chem. 2015;5(2):81-9. doi: 10.4172/2161-0444.1000247.

Yousaf AM, Mustapha O, Kim DW, Kim DS, Kim KS, Jin SG. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Int J Nanomedicine. 2016;11:213-21. doi: 10.2147/IJN.S97496, PMID 26834471.

Fitriani L, Afriyanti I, Afriyani A, Ismed F, Zaini E. Solid dispersion of usnic acid–HPMC 2910 prepared by spray drying and freeze drying techniques. Orient J Chem. 2018;34(4):2083-8. doi: 10.13005/ojc/3404048.

Rowe R, Sheskey P, Quinn M. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009.

Umar S, Bandaro NP, Anggraini D, Zaini E. Multicomponent crystal of fenofibric acid-saccharin: characterization and antihyperlipidemic effectiveness. Adv Health Sci Res. 2021;40:104-9. doi: 10.2991/ahsr.k.211105.015.

Sosnik A, Seremeta KP. Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers. Adv Colloid Interface Sci. 2015;223:40-54. doi: 10.1016/j.cis.2015.05.003, PMID 26043877.

Rabiej S. A comparison of two X-ray diffraction procedures for crystallinity determination. Eur Polym J. 1991 Jan 1;27(9):947-54. doi: 10.1016/0014-3057(91)90038-P.

Zaini E, Khairun Nisak R, Dwi Utami R, Fitriani L, Ismed F. Effect of milling on physicochemical properties of usnic acid isolated from Usnea sp. Orient J Chem. 2017 Dec 1;33(6):3031-6. doi: 10.13005/ojc/330641.

Hiendrawan S, Veriansyah B, Tjandrawinata RR. Solid-state properties and solubility studies of novel pharmaceutical co-crystal of itraconazole. Int J Appl Pharm. 2018;8(10):5.

Variankaval N, McNevin M, Shultz S, Trzaska S. High-throughput screening to enable salt and polymorph screening, chemical purification, and chiral resolution. In: Comprehensive organic synthesis. 2nd ed; 2014.

Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012;2012:195727. doi: 10.5402/2012/195727. PMID 22830056.

Schafroth N, Arpagaus C, Jadhav UY, Makne S, Douroumis D. Nano and microparticle engineering of water-insoluble drugs using a novel spray-drying process. Colloids Surf B Biointerfaces. 2012 Feb 1;90:8-15. doi: 10.1016/j.colsurfb.2011.09.038, PMID 22019455.

Bain DF, Munday DL, Smith A. Solvent influence on spray-dried biodegradable microspheres. J Microencapsul. 1999 Jan 1;16(4):453-74. doi: 10.1080/026520499288915, PMID 10420331.