Abstract
Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.
Highlights
Absorption of a drug from oral route majorly depends up on the dissolution of the drug from the formulations into GI fluids followed by its permeation
Saturation solubility study indicates that ambrisentan was poorly soluble in water, showing 7.347±0.003 μg/ml of solubility in distilled water
A linear increase in the solubility of drug was seen with an increasing concentration of hydrophilic carriers in water
Summary
Absorption of a drug from oral route majorly depends up on the dissolution of the drug from the formulations into GI fluids followed by its permeation. Bioavailability of drugs from oral route depends on their solubility as well as permeability. In order to achieved desired pharmacological response, the solubility of the drug is one of the important parameter [1, 2]. Low bioavailability of the drugs are generally associated with poor aqueous solubility which is turn required the higher dose and repeated administration of drug. Bioavailability of poorly water-soluble drugs can be increased by increasing its aqueous solubility and dissolution rate [3]. Solid dispersion is one of the widely utilized technology in the improvement of the solubility, dissolution and bioavailability of poorly water-soluble drugs [4, 5]
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