Thermal, spectroscopic, and dissolution studies of ketoconazole–Pluronic F127 system

Abstract

One strategy for improving the dissolution of poorly water soluble drugs is to prepare solid dispersions such as binary mixtures with hydrophilic carriers. These mixtures are generally characterized by better solubility than those of the individual components from which they are formed. In the present study, solid dispersions of ketoconazole (KET) with Pluronic F127 (PLU) were prepared by the grinding method. Solid-liquid equilibria in the system being studied were investigated by differential scanning calorimetry. A phase diagram for the whole range of compositions was constructed. The investigation revealed that ketoconazole and Pluronic F127 form a simple eutectic system containing 4.4 % w/w of ketoconazole at the eutectic point. The results of Fourier transform infrared spectroscopy and X-ray powder diffractometry studies of obtained mixtures suggest that there is no drugcarrier interaction and both components are crystalline in the solid dispersion with the whole range of composition. The prepared mixtures show an appreciable improvement of the dissolution rate of KET in 0.5 % w/v sodium lauryl sulfate. The improvement of the dissolution rate of drug is additionally increased by effective solubilization.

Development and optimization of ketoconazole oral strips by means of continuous hot-melt extrusion processing

“…In an early investigation, the group found that the addition of plasticizers, such as triethyl citrate, PEG 2000/8000, or acetyltributyl citrate, allowed the manufacture of thin, flexible and stable films when hydroxypropyl cellulose (HPC) was used as film forming polymer . It was shown that the increase in the molecular weight of HPC decreased the release of drugs from extruded films, which resulted in dissolution profiles exhibiting zero‐order drug release …”

“…Due to its very poor water solubility (17 μg/ml) and high permeability, KTZ is classified as biopharmaceutics classification system (BCS) class II drug. Increasing the solubility of KTZ is a challenging task as it significantly reduces the oral bioavailability of the drug and thus the therapeutic effectiveness . We report, to the best of our knowledge, a new case to manufacture KTZ‐based oral strips using inorganic excipients via a continuous HME processing and the physicochemical characterization of the developed strips where the novelty of this article lies.…”

“…[13] It was shown that the increase in the molecular weight of HPC decreased the release of drugs from extruded films, which resulted in dissolution profiles exhibiting zero-order drug release. [14,15] Ketoconazole (KTZ) is an antifungal agent mainly used for the treatment of local and systemic fungal infections in various forms (e.g. oral tablets, topical creams, gels, aerosols, suspensions and shampoos).…”

“…Increasing the solubility of KTZ is a challenging task as it significantly reduces the oral bioavailability of the drug and thus the therapeutic effectiveness. [15] We report, to the best of our knowledge, a new case to manufacture KTZ-based oral strips using inorganic excipients via a continuous HME processing and the physicochemical characterization of the developed strips where the novelty of this article lies. The distribution of the drug particles on the surface of the manufactured oral strips is also investigated as well as the strips' hydration/swelling, mucoadhesion and mechanical properties.…”

Physicochemical characterization and dissolution studies of acyclovir solid dispersions with Pluronic F127 prepared by the kneading method

“…It was recently shown by our group and other authors that Pluronic F127 can be used successfully as a carrier for dissolution rate improvement of poorly water-soluble drugs, including simvastatin (18) and ketoconazole (19)(20)(21)(22). The aim of this study was to increase acyclovir dissolution rate by preparing physical mixtures and solid dispersions of anhydrous acyclovir form I (ACV) with Pluronic F127 (PLU).…”