Dissolution Enhancement of Eplerenone using Solvent Melt Method

Author(s): Vijay Agarwal*, Vipin Kumar, Pankaj K. Sharma

Journal Name: Drug Delivery Letters

Volume 11 , Issue 1 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Eplerenone (EPL) is a BCS class II drug, thus, having poor water solubility. The poor water solubility of this drug leads to poor dissolution and ultimately shows poor bioavailability. To overcome this problem, the solid dispersion of EPL was prepared in this study.

Methods: This was accomplished by using the solvent melt method as the solid dispersion technique. In this method, Pluronic F-68 and F-127 were used as the carrier and different formulations were prepared using varying ratios of a drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of drug solution and carrier was prepared at 70°C, using the digital magnetic stirrer. The resultant mixture was dried at 40°C in a hot air oven and optimized EPL-solid dispersion was undergone for their characterization using drug content, drug entrapment efficiency (%) and drug loading content (%), Scanning Electron Microscopy (SEM), Infra-Red spectroscopy, Differential Scanning Calorimetry (DSC), stability study and in-vitro dissolution studies.

Results: The result indicated that there was no interaction between EPL and Pluronics (Pluronic F-68 & F-127), and optimized formulation (P127-2) of EPL-solid dispersion had encapsulation efficiency > 95%. Experimental work also showed that optimized formulation has 31.7% of drug loading content which was greater than other existing solid dispersion having less than 30% of drug loading content. Out of different batches, the optimized batch exhibits the faster dissolution rate in comparison to other batches. It released the almost total amount of drug (98.96%) in 30 minutes. The stored ESM-solid dispersion also exhibited remarkable stability and remains in a solid state, when it was exposed to 25°C/60% relative humidity and room temperature (38ºC) for two months. Such stability was confirmed by DSC method. The DSC thermogram of optimized formulation exhibited a melting endotherm at an onset temperature of 160°C, a peak temperature of 165°C and a heat of fusion of 25.68 J/gm. Similarly, the DSC thermogram of the physical mixture of bulk EPL/- pluronic F-127 also exhibited the onset of temperature at 165°C, and a peak temperature at 171°C. Thus, the result indicated that both samples showed almost similar DSC pattern and no sample altered its state after the treatment of temperature and humidity used in stability testing. SEM study was also performed in this research and the result indicated that the particle size of optimized formulation was varied, having irregular matrices due to the porous nature of the carrier.

Conclusion: Based on different findings, it can be concluded that the solvent melt method could be a potential method for preparing the solid dispersion of EPL like BCS class-II Drugs and will be able to solve the dissolution and solubilization related problem of poorly soluble drugs.

Keywords: Solid dispersion, eplerenone, pluronics, dissolution enhancement, solubility, solvent melt.

[1]
Nikghalb, L.A.; Singh, G.; Singh, G.; Kahkeshan, K.F. Solid dispersion : Methods and polymers to increase the solubility of poorly soluble drugs. J. Appl. Pharm. Sci., 2012, 2(10), 170-175.
[2]
Tran, P.; Pyo, Y.C.; Kim, D.H.; Lee, S.E.; Kim, J.K.; Park, J.S. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics, 2019, 11(3), 1-26.
[http://dx.doi.org/10.3390/pharmaceutics11030132] [PMID: 30893899]
[3]
Chaudhary, A.; Nagaich, U.; Gulati, N.; Sharma, V.; Khosa, R. Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications. J. Adv. Pharm. Educ. Res., 2012, 2(10), 32-67.
[4]
Pawar, A.R.; Choudhary, P.D. Novel techniques for solubility, dissolution rate and bioavailability enhancement of class II and IV drugs. Asian J. Biomed. & Phar. Sci., 2012, 2(13), 9-14.
[5]
Mohammed, S.S.; Pranush, K.V.; Reddy, G.V. Improvement of solubility of omeprazole magnesium by solid dispersion and slugging method. Asian Journal of Research in Biological and Pharmaceutical Science., 2013, 1(2), 83-89.
[6]
Sharma, P.; Kapoor, A.; Bhargava, S. A review on: Solubility enhancement by implementing solid dispersion technique for poorly water soluble drug. Res. J. Pharm. Biol. Chem. Sci., 2012, 3, 847-860.
[7]
Rajmalle, K.; Zameerruddin, M.; Jadhav, S.; Kadam, V.; Bharkad, V. Recent approaches solubility and dissolution enhancement of atorvastatin: A review. World J. Pharm. Sci., 2014, 3, 534-344.
[8]
Dhirendra, K.; Lewis, S.; Udupa, N.; Atin, K. Solid dispersions: A review. Pak. J. Pharm. Sci., 2009, 22(2), 234-246.
[PMID: 19339238]
[9]
Sapkal, S.B.; Shinde, S.A.; Darakhe, R.A.; Shrikhande, V.N. solid dispersion of valsartan for solubility improvement using β cyclodextrin. J. Bioequivalence Bioavailab., 2018, 5(6), 313-319.
[10]
Savjani, K.T.; Gajjar, A.K.; Savjani, J.K. Drug solubility: Importance and enhancement techniques. ISRN Pharm., 2012, 2012, 195727.
[http://dx.doi.org/10.5402/2012/195727] [PMID: 22830056]
[11]
Khadka, P.; Ro, J.; Kim, H.; Kim, I.; Kim, J.T.; Kim, H.; Cho, J.M.; Yun, G.; Lee, J. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian J. Pharm. Sci., 2014, 9, 304-316.
[http://dx.doi.org/10.1016/j.ajps.2014.05.005]
[12]
Tam, T.S.; Wu, M.H.; Masson, S.C.; Tsang, M.P.; Stabler, S.N.; Kinkade, A.; Tung, A.; Tejani, A.M. Eplerenone for hypertension. Cochrane Database Syst. Rev., 2017, 2, CD008996.
[PMID: 28245343]
[13]
Chatziralli, I.; Vlachodimitropoulou, A.; Daoula, C.; Vrettou, C.; Galani, E.; Theodossiadis, G.; Theodossiadis, P. Eplerenone in the treatment of central serous chorioretinopathy: A review of the literature. Int. J. Retina Vitreous, 2018, 4, 33.
[http://dx.doi.org/10.1186/s40942-018-0137-8] [PMID: 30250750]
[14]
Argade, P.S.; Magar, D.D.; Saudagar, R.B. Solid dispersion: Solubility enhancement technique for poorly water soluble drugs. J. Adv. Pharm. Educ. Res., 2013, 3(4), 427-439.
[15]
Shrestha, S.; Sudheer, P.; Bharani, S.; Soans, S.D.A. Review: Solid dispersion, a technique of solubility enhancement. J. Pharma Res., 2017, 16(1), 25-31.
[http://dx.doi.org/10.18579/jpcrkc/2017/16/1/112470]
[16]
Sultana, S.; Saifuddin, A.H.M. Review article: Solid dispersion currently practiced in pharmaceutical field. Int. J. Adv. Res. Technol., 2016, 5(3), 170-175.
[17]
Yadav, B.; Tanwar, Y.S. Applications of solid dispersions. J. Chem. Pharm. Res., 2015, 7(2), 965-978.
[18]
Neil, M.J.O. The Merck IndexMerck Research Laboratories, White House Station: NJ, 2006.
[19]
Sweetman, S.C. Martindale - The Complete drug Reference, Vol-I; Pharmaceutical press: London, 2007.
[20]
Kurmi, R.; Mishra, D.K.; Jain, D.K. Solid Dispersion: A novel means of solubility enhancement. J. Crital. Rev., 2016, 3(1), 1-8.
[21]
Khames, A. Formulation and characterization of eplerenone nanoemulsion liquisolids, an oral delivery system with higher release rate and improved bioavailability. Pharmaceutics, 2019, 11(1), 1-18.
[http://dx.doi.org/10.3390/pharmaceutics11010040] [PMID: 30669353]
[22]
Ozdemir, S.; Celik, B.; Sumer, B.; Acar, E.T.; Uner, M. Eplerenone nanoemulsion for treatment of hypertension. Part I: Experimental design for optimization of formulations and and physical characterization. J. Drug Deliv. Sci. Technol., 2018, 45, 357-366.
[http://dx.doi.org/10.1016/j.jddst.2018.03.011]
[23]
Naik, G.N.; Sunder, R.S. Enhancement of solubility and dissolution profile of eplerenone by liquisolid compacts using novel excipients. Int. J. Pharm. Sci. Res., 2020, 11(6), 2892-2898.
[24]
Kendre, P.N.; Chaudhari, P.D. Effect of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer on bioadhesion and release rate property of eplerenone pellets. Drug Dev. Ind. Pharm., 2017, 43(5), 751-761.
[http://dx.doi.org/10.1080/03639045.2016.1220570] [PMID: 27494543]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 11
ISSUE: 1
Year: 2021
Published on: 07 October, 2020
Page: [71 - 80]
Pages: 10
DOI: 10.2174/2210303110999201007164919
Price: $25

Article Metrics

PDF: 15
HTML: 1