Dissolution Rate Enhancement and Physicochemical Characterization of a Fenofibric Acid–Nicotinamide Eutectic Mixture
doi.org/10.26538/tjnpr/v5i9.14
Keywords:
Fenofibric acid, Nicotinamide, Eutectic mixture, Solubility, Dissolution ratesAbstract
Fenofibric acid is a potent lipid-lowering agent that is used clinically in severe hypertriglyceridemia, primary hyperlipidemia, and mixed dyslipidemia. Fenofibric acid is a poorly soluble drug which is classified as a Biopharmaceutical Classification System (BCS) class II. The purpose of the present study was to improve the solubility and dissolution rate of the poorly soluble drug fenofibric acid (FA) by the formation of a simple eutectic mixture with nicotinamide (NIC). A simple eutectic mixture of FA and NIC was prepared using the solvent-drop grinding method. A binary phase diagram of FA and NIC in various molar ratios was constructed by thermal analysis differential scanning calorimetry (DSC). Solid-state characterization was carried out using powder X-ray diffraction (PXRD) analysis, differential scanning calorimetry, Fourier transform-infrared spectroscopy analysis, scanning electron microscopy analysis, and apparent solubility test. The in vitro dissolution rate of the simple eutectic mixture in an aqueous medium was determined using a type I USP apparatus. The binary phase diagram demonstrated that FA and NIC form a simple eutectic mixture at a molar ratio of 0.3:0.7. The eutectic mixture melted at an endothermic peak of 112.9°C. The PXRD pattern of the eutectic mixture was representative of each intact component (FA and NIC). SEM microscopic analysis showed that new crystal habits were formed. The solubility and dissolution rate of FA from the eutectic mixture were improved significantly compared to intact FA.
References
Alagona Jr P. Fenofibric acid: a new fibrate approved for use in combination with statin for the treatment of mixed dyslipidemia. Vasc Health Risk Manag. 2010; 6 (1): 351-362.
Papich MG, Martinez MN. Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls. The AAPS J. 2015; 17(4): 948-964.
Kim KS, Kim JH, Jin SG, Kim DW, Kim DS, Kim JO, Yong CS, Cho KH, Li DX, Woo JS, & Choi HG. Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer. Arch Pharm Res. 2016; 39(4): 531–538.
Yousaf AM, Ramzan M, Shahzad Y, Mahmood T, Jamshaid M. Fabrication and in vitro characterization of fenofibric acid-loaded hyaluronic acid–polyethylene glycol polymeric composites with enhanced drug solubility and dissolution rate. Int J Polym Mater Polym Biomater. 2019; 68(9): 510-515.
Cink RD, Paterson JB, Gao JY, Long MA, Morris JB, Rosenberg J. Salts of fenofibric acid and pharmaceutical formulations thereof. US Patent Published online 2004.
Windriyati YN, Sumirtapura YC, Pamudji JS. Dissolution enhancement and physicochemical characterization of fenofibric acid in surface solid dispersion with croscarmellose sodium. Marmara Pharm J. 2019; 23(2): 315-325.
Suhery WN, Sumirtapura YC, Pamudji JS, Mudhakir D. Development and characterization of self-nanoemulsifying drug delivery system (Snedds) formulation for enhancing dissolution of fenofibric acid. J Res Pharm. 2020; 24(5): 738-747.
Cherukuvada S and Nangia A. Eutectics as improved pharmaceutical materials: design, properties and characterization. Chem Commun. 2014; 50(8): 906-923.
Sunita S, Budhwar V, Choudhary M. Pharmaceutical Eutectics: A Promising Drug Delivery System. Res J Pharm Technol. 2020; 13(11) 5515-5523.
Brahamdutt B, Narwal S, Kumar A, Chaudhary M, Budhwar V. Formulation of Eutectic mixture of Curcumin with Salicylic Acid for improving its Dissolution Profile. Res J Pharm Technol. 2021; (October 2020): 1875-1879.
Haneef J and Chadha R. Antioxidant-Based Eutectics of Irbesartan: Viable Multicomponent Forms for the Management of Hypertension. AAPS PharmSciTech. 2018; 19(3): 1191-1204.
Fernandes RP, de Carvalho ACS, Ekawa B, do Nascimento ALSC, Pironi A M, Chorilli M, & Caires FJ. Synthesis and characterization of meloxicam eutectics with mandelic acid and saccharin for enhanced solubility. Drug Dev Ind Pharm.
Zaini E, Rachmaini F, Armin F, Fitriani L. Preparation and characterization of binary mixture of efavirenz and nicotinamide. Orient J Chem. 2015; 31(4): 2271-2276.
Patel RD, Raval MK, Bagathariya AA, Sheth NR. Functionality improvement of Nimesulide by eutectic formation with nicotinamide: Exploration using temperaturecomposition phase diagram. Adv Powder Technol. 2019; 30(5): 961-973.
Zaini E, Wahyuni YS, Halim A, Yuliandra Y. Preparation of eutectic mixture of ketoprofen and nicotinamide for enhanced dissolution rate. Int J Pharm Sci Rev Res. 2015;
(1): 161-164.
Stojanovska PM, Geskovski N, Petrushevski G,
Chachorovska M, Krsteska L, Ugarkovic S, & Makreski P.
Solid-state interaction of ibuprofen with magnesium stearate
and product characterization thereof. Drug Dev Ind Pharm.
; 46(8): 1308–1317.
Dalal N, Buckner IS, Wildfong PLD. Experimental
Determination and Theoretical Calculation of the Eutectic
Composition of Cefuroxime Axetil Diastereomers. AAPS
Pharm Sci Tech. 2017; 18(7): 2570-2578.
Erizal, Cahyati SY, Nurono SS, Halim A. Effect of milling
on solid state transformation of sulfamethoxazole. Int J
Pharmacol. 2008; 4(2): 140-144.
Saha S, Desiraju GR. Acid···Amide Supramolecular Synthon
in Cocrystals: From Spectroscopic Detection to Property
Engineering. J Am Chem Soc. 2018; 140(20): 6361-6373.
Pereira-da-Silva MA and Ferri FA. Scanning Electron
Microscopy. In: Oliveira ON de, Róz JFM, Da FLLL, Luzia
A, eds. Nanocharacterization Techniques. Elsevier; 2017. 1-
p.
Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S.
Formulation design for poorly water-soluble drugs based on
biopharmaceutics classification system: basic approaches
and practical applications. Int J Pharm. 2011; 420(1): 1-10.
Chaturvedi K, Shah HS, Nahar K, Dave R, Morris KR.
Contribution of Crystal Lattice Energy on the Dissolution
Behavior of Eutectic Solid Dispersions. Am Chem Soc
Omega. 2020; 5(17): 9690-9701.
Haneef J, Ali S, Chadha R. Emerging Multi-Drug Eutectics:
Opportunities and Challenges. AAPS Pharm Sci Tech. 2021;
(2): 66.
Chadha R, Sharma M, Haneef J. Multicomponent solid forms
of felodipine: preparation, characterisation, physicochemical
and in-vivo studies. J Pharm Pharmacol. 2017; 69(3): 254-
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
