Background:
Eplerenone (EPL) is a BCS class II drug, thus, having the poor water solubility. The poor water
solubility of this drug leads to the poor dissolution and ultimately shows the 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 was used as the carrier and different formulations were prepared using the varying in ratio of a
drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of drug solution and carrier were prepared at 70oC, using the digital
magnetic stirrer. The resultant mixture was dried at 40oC in 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 Calorimetery (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 have 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 of other batches. It released the almost total amount of drug (98.96%) in 30 minutes. The
stored ESM-solid dispersion also exhibited their remarkable stability and remains in solid state, when it was exposed to
25oC/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 onset temperature of 160oC, a peak
temperature of 165oC and a heat of fusion of 25.68 J/gm. Simirly, DSC thermogram of physical mixture of bulk
EPL/pluronic F-127 also exhibited the onset of temperature at 165oC, and a peak temperature at 171oC. Thus, result
indicated that both sample showed the almost similar DSC pattern and no one sample alter their state after the treatment of
temperature and humidity used in stability testing. SEM study was also performed in this research and result indicated that
the particle size of optimized formulation was varied and having the irregular matrices due to porous nature of the carrier.
Conclusion:
Based on different findings it can be concluded that 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.
Approaches of increasing oral bioavailability of class ii active pharmaceutical ingredients in accordance with the biopharmaceutical classification system
