ABSTRACT
Proton magnetic resonance spectroscopy ((1)HNMR) studies on inclusion compounds of zaleplon with hydroxypropyl-ß- cyclodextrin (HPßCD) were carried out in order to elucidate the strength and binding mode of association. Chemical shift measurements revealed that inclusion complexes of zaleplon and HPßCD were formed by penetration of aromatic rings into the HPßCD cavity from the wider rim side with deep penetration of the amide-substituted ring while inclusion of the cyano-substituted pyrazole ring was shallow. A higher magnitude of ΔδH-3' and ΔδH-5' protons of HPßCD indicated higher stability of the lyophilized product than the kneaded one. Even from the values of ΔδH-5'/ΔδH-3', it could be concluded that zaleplon deeply penetrated inside the HPßCD cavity in the lyophilized product as compared to the kneaded product. The stoichiometry of the inclusion complexes was assessed to be a 1:1 molar ratio with an AL-type of phase solubility curve and a stability constant of 57.89 ± 1.82 M-1, according to Higuchi and Connors. In the case of dissolution experiments, a lyophilized product displayed a higher release rate of zaleplon (DE30: 77.64 ± 5.74) than the kneaded complex and physical mixture.
Subject(s)
Protons , Solubility , Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform InfraredABSTRACT
Solid dispersions of the poorly water-soluble drug ezetimibe were prepared with a surfactant, Pluronic 188 in different ratios and characterized by FTIR, XRD, DSC and dissolution studies. The melting method was employed to prepare the solid dispersions whereas a physical mixture (1:3) was prepared by co-grinding the individual components in a mortar. Physical studies demonstrated a significant reduction in crystallinity with a possibility of presence of amorphous character of drug in the solid dispersions of ezetimibe. Among all binary systems studied, the 1:3 proportion of ezetimibe: Pluronic 188 showed fastest dissolution rate (DE90: 73.38% +/- 3.95) suggesting optimum ratio of the surfactant used.
Subject(s)
Anticholesteremic Agents/chemistry , Azetidines/chemistry , Calorimetry, Differential Scanning , Ezetimibe , Kinetics , Poloxamer/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , Surface-Active Agents/chemistry , X-Ray DiffractionABSTRACT
The objective of the present work was to improve the dissolution rate of a poorly water-soluble drug, bicalutamide, by a solid dispersion technique. The solid dispersion systems of bicalutamide were prepared with poloxamer F68 in 1:1, 1:3, and 1:5 ratios using the melting method. The interaction of drug with polymer was evaluated by TLC, FTIR, and powder XRD. The results of powder XRD showed a significant decrease in the crystallinity of drug in the binary systems of bicalutamide. All binary systems of bicalutamide showed faster dissolution than pure drug alone (p < 0.001). However, among all binary systems studied, 1:1 proportion of bicalutamide : poloxamer was found to be excellent for dissolution enhancement (DP30: 99.98% +/- 3.9) of bicalutamide. The higher ratios of poloxamer F68 (1:3 and 1:5) had retarded the release of drug from their corresponding binary systems which might be due to its gelling property in higher concentration.
Subject(s)
Anilides/chemistry , Nitriles/chemistry , Tosyl Compounds/chemistry , Chemistry, Pharmaceutical , Chromatography, Thin Layer , Excipients , Kinetics , Poloxamer/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
A simple, sensitive, rapid, accurate and precise spectrophotometric method has been developed for the estimation of bicalutamide in bulk and pharmaceutical dosage forms. Bicalutamide shows maximum absorbance at 272 nm with molar absorptivity of 2.3399×10(4) l/mol/cm. Beer's law was obeyed in the concentration range of 1.5-18 µg/ml. The limit of detection and limit of quantification were found to be 0.1 and 0.4 µg/ml, respectively. Results of analysis were validated statistically and by recovery studies.
