Physicochemical Characterization and Dissolution Study of Solid Dispersions of Ketoconazole with Nicotinamide

Abstract

Purpose: The aim of the present study was to improve the solubility and dissolution rate of a poorly watersoluble drug ketoconazole using solid dispersion technique. Methods: Solid dispersions of ketoconazole were prepared in ratios of 90 : 10, 70 : 30, 50 : 50, 30 : 70 and 10 : 90 by the melting method using nicotinamide as carrier. These solid dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy to ascertain if there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure ketoconazole, physical mixtures and solid dispersions. Results: Solubility studies indicated that nicotinamide increased significantly the solubility of ketoconazole in water. The Gibbs free energy (D DG°t r ) values were negative indicating the spontaneous nature of ketoconazole solubilization, and it decreased with increase in concentration of the carrier, demonstrating that the reaction became more favorable as the concentration of the carrier increased. The cumulative release of ketoconazole within 120 min from solid dispersion at a drug-tonicotinamide ratio of 10 : 90 (w/w) was 6 times higher than the pure drug in phosphate buffer of pH 6.8. Conclusion: Solid state characterization indicated that there is no interaction between ketoconazole and nicotinamide in the solid state. In contrast to the very slow dissolution rate of pure ketoconazole, the dispersion of the drug in nicotinamide considerably enhanced the dissolution rate. The drug dissolution rate was highest at a drug-tonicotinamide ratio of 10 : 90 (w/w).

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

“…The absorbance of ketoconazole was recorded against a blank solution of methanol at 231 nm to avoid any interference. 16 The entrapment efficiency was calculated using the following equation:…”

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“…The value of gas constant (R) is 8.31 J/K/mol and T is temperature in degree Kelvin. [16] Preparation of PM PM of OLM and Poloxamaer 407 were prepared by simple mixing method using glass morter and pestle in different ratios such as (1:0.5 PM1, 1:1 PM2, 1:1.5 PM3, 1:2 PM4 w/w).…”

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

“…Because of low crystallization tendency and strong drug-carrier interaction, solid dispersion of ketoconazole in HPMC-AS outperformed all others (18). Solid dispersion of ketoconazole in nicotinamide improves its solubility and dissolution (19). Solid dispersions of atorvastatin calcium were prepared in Soluplus® (20), modified locust bean gum (21), polyvinylpyrrolidone vinyl acetate (22), and poly(ethylene glycol) 6000 (23) to improve its solubility, dissolution, and bioavailability.…”