Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation
DOI:
https://doi.org/10.37285/ijpsn.2020.13.5.7Abstract
Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension. From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.
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Keywords:
Fenofibrate, Solid dispersions, solvent casting, In vitro dissolution, DSC, XRD, Oral bioavailability, Pharmacokinetics
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Ahuja N, Katare P and Singh B (2007). Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur J Pharm Biopharm 65: 26-38.
Arun B and Narendar D (2015). Enhancement of solubility and dissolution rate of trandolapril sustained release matrix tablets by liquisolid compact approach. Asian J Pharma 9(4): 290-297.
Badens E, Majerik V and Horváth G (2009). Comparison of solid dispersions produced by supercritical antisolvent and spray-freezing technologies. Int J Pharm 377: 25-34.
Bankar PV and Mahatma OP (2012). Improved dissolution rate of leflunomide using hydroxypropyl- β-cyclodextrin inclusion complexation by freeze-drying method. Int J Drug Deliv 4: 498-506.
Benita S (2005). Microencapsulation: Methods and Industrial Applications, Second ed., CRC Press, USA.
Caliph SM, Charman WN and Porter CJH (2000). Effect of short, medium, and long chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph cannulated and non-cannulated rats. J Pharm Sci 89: 1073-1084.
Cavalli R, Caputo O, Carlotti ME, Trotta M, Scarnecchia C and Gasco MR (1997). Sterilization and freeze-drying of drug-free and drug loaded solid lipid nanoparticles. Int J Pharm 148: 47-54.
Chella N, Daravath B, Kumar D and Tadikonda RR (2014). Formulation and pharmacokinetic evaluation of polymeric dispersions containing valsartan. Eur J Drug Metab Pharmacokinet 41: 517-526.
Craig DQM (2002). The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 231: 131-144.
Dhirendra K, Lewis S, Udupta N and Atin K (2009), Solid dispersions: a review. Pak J Pharm Sci 22: 234-246.
Ding B, Chen H, Wang C, Zhai Y and Zhai G (2013). Preparation and in vitro evaluation of apigenin loaded lipid nanocapsules. J Nanosci Nanotechnol 13: 6546-6552.
Ettireddy S and Dudhipala N (2017). Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine. Int J Pharm Sci Nanotech 10(3): 3752-3757.
Guay D (2008). Micronized fenofibrate: a new fibric acid hypolipidemic agent. Ann Pharmacother 33: 1083-1103.
Johnson PH and Nale P (2001). Pharmacist’s Drug Handbook, Springhouse Corporation and American Society of Health-System Pharmacists, USA.
Kathroj N, Dudhipala N and Veerabrahma K (2017). Development of olmesartan medoxomil optimized nanosuspension using Box-Behnken design to improve oral bioavailability. Drug Dev Ind Pharm 43(7): 1186-1196.
Leuner C and Dressman J (2000). Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50: 47-60.
Mennini N, Maestrelli F, Cirri M and Mura P (2016). Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and larginine aimed to improve the drug solubility. J Pharm Biomed Anal 129: 350-358.
Ming-Thau S, Ching-Min Y and Sokoloski TD (1994). Characterization and dissolution of fenofibrate solid dispersion systems. Int J Pharm 103: 137-146.
Modi A and Tayade P (2006). Enhancement of dissolution profile by solid dispersion (Kneading) technique. AAPS Pharm Sci Tech 7: E1-E6.
Narendar D, Arjun N, Dinesh S and Karthik J (2016). Biopharmaceutical and Preclinical Studies of efficient oral delivery of zaleplon as semisolid dispersions with self-emulsifying lipid surfactants. Int J Pharm Sci Nanotech 9(1): 3102-3111.
Narendar D, Chinna Reddy P, Sunil R and Madhusudan Rao Y (2012). Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers. Int J Drug Deli 4: 462-469.
Narendar D and Kishan V (2015). Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Dev Ind Pharm 41(12): 1968-77.
Narendar D and Kishan V (2016). Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Delivery 23(2): 395-404.
Narendar D and Kishan V (2017). Improved anti-hyperlipidemic activity of rosuvastatin calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. Euro J Pharm Biopharm 110 (1): 47-57.
Palem CR, Narendar D, Satyanarayana G and Varsha BP (2016). Development and optimization of Atorvastatin calcium-cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design Int J Pharm Sci Nanotech 9(2): 3170-3181.
Perrut M, Jung J and Leboeuf F (2005). Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes: part I: micronization of neat particles. Int J Pharm 288: 3-10.
Pitta S, Dudhipala N, Narala A and Veerabrahma K (2018). Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm 44(3): 484-492.
Sam M, David JB,, Luca C and Lisbeth I (2019). Application of permeation enhancers in oral delivery of macromolecules: an update. Pharmaceutics 11(1): 41.
Sandeep V, Narendar D, Arjun N and Kishan V (2016). Lacidipine Loaded Solid Lipid Nanoparticles for Oral Delivery: Preparation, Characterization and In vivo Evaluation, Int J Pharm Sci Nanotech 9: 3524-3530.
Schurr PE, Schultz JR and Parkinson TM (1972). Triton-induced hyperlipidemia in rats as an animal model for screening hypolipidemic drugs. Lipids 7: 68-74.
Serajuddin A (1999). Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharmacol Sci 88: 1058-1066.
Serajuddin ABT (2007). Salt Formation to Improve Drug Solubility. Adv Drug Deliv Rev 59(7): 603-616.
Suvarna G, Narender D and Kishan V (2015). Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles. Int J Pharm Sci Nanotech 8(1): 2779-2785.
Tang N, Lai J, Chen Y, Lu Y and Wu W (2009). Fenofibrate solid dispersion pellets prepared by fluid-bed coating: physical characterization, improved dissolution and oral bioavailability in beagle dogs. J China Pharm Sci 18: 156-161.
Teslev A (2014). Towards the application of solid dispersions for improving the biopharmaceutical characteristics of drugs, Pharm. Technol. 2: 18-21.
Thirumalesh C, Dinesh S, Narendar D and Nagaraj B (2020). T Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharma nanotech 8(2): 148-160.
Thirupathi G, Swetha E and Narendar D (2017). Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats. Drug res 67(03): 163-169.
Vasconcelos T, Sarmento B and Costa P (2007). Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 12: 1068-1075.
Venkatanaidu K, Arun B and Narendar D (2015). Fabrication of efavirenz freeze dried nanocrystals: formulation, physic-chemical characterization, in vitro and ex vivo evaluation. Adv Sci Engineer Med 7(5): 385-392.
Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, Higaki K and Kimura T (2003). Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm 267: 79-91.
Yoshihashi Y, Iijima H, Yonemochi E and Terada K (2006). Estimation of physical stability of amorphous solid dispersion using differential scanning calorimetry. J Therm Anal Calorim 85: 689-692.
Zhang Y, Che E, Zhang M, Sun B, Gao J, Han J and Song Y (2014). Increasing the dissolution rate and oral bioavailability of the poorly water-soluble drug valsartan using novel hierarchical porous carbon monoliths. Int J Pharm 473: 375-383.
