Dissolution Enhancement of Eplerenone using Solvent Melt Method

Abstract

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.

Eplerenone repurposing in management of chorioretinopathy: Mechanism, nanomedicine‐based delivery applications and future trends

“…Their results reported massive enhancement in EPL bioavailability in vivo, with 1276.26% greater relative bioavailability for the pellet formulation with EPL loaded solid dispersion compared to that of the pellets containing plain EPL 72 . In another study, Agrawal et al 73 succeeded to prepare EPL solid dispersions using a carrier mixture of Pluronic F127 and Pluronic F68 via the solvent melt method. Their results confirmed that the optimized solid dispersion exhibited fast dissolution with almost 98.96% drug dissolved in 30 minutes.…”

“…In-situ gel mainly applied for drugs with fast elimination rate (short elimination half-life). EPL was prepared in an oral in situ gel formulation, 74 using different polymers such as sodium alginate, calcium carbonate, sodium citrate, xanthan gum, guar gum and karaya gum. The in situ gel system prepared using guar gum as a polymer was reported to achieve successful sustainment of EPL release.…”