Proton magnetic resonance ((1)HNMR) spectroscopy and physicochemical studies of zaleplon-hydroxypropyl-ß-cyclodextrin inclusion compounds.

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.

3D QSAR investigations on locomotor activity of 5-cyano-N1,6-disubstituted 2-thiouracil derivatives.

Three dimensional quantitative structure activity relationship (3D QSAR) investigations were carried out on a series of 5-cyano-N1,6-disubstituted 2-thiouracil derivatives for their locomotor activity. The structures of all compounds were built on a workspace of VlifeMDS3.5 molecular modeling software and 3D QSAR models were generated by applying a partial least square (PLS) linear regression analysis coupled with a stepwise variable selection method. Both derived models were found to be statistically significant in terms of regression and internal and external predictive ability (r(2) = 0.9414 and 0.8511, q(2) = 0.8582 and 0.6222, pred_r(2) = 0.5142 and 0.7917). The QSAR models indicated that both electrostatic and steric interaction energies were contributing significantly to locomotor activity of thiouracil derivatives.

Improvement in the dissolution profile of diacerein using a surfactant-based solid dispersion technique.

In an attempt to improve the dissolution rate of poorly aqueous soluble diacerein (DCN), solid dispersions (SDs) were prepared with a surfactant Pluronic® F 127 (PXMR) at drug to polymer ratios of 1:0.5, 1:1.5, and 1:2.5 (w/w) by an ordinary melting technique. The interaction of DCN with PXMR in all solid binary systems was evaluated by thin layer chromatography (TLC), Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) studies. TLC indicated an absence of chemical interaction of DCN with PXMR whereas FTIR studies demonstrated an existence of strong hydrogen bonding between them. A uniform molecular dispersion of DCN was observed in DSC thermograms, and this finding was further supported by loss of the crystalline and irregular shape of DCN detected in SEM photomicrographs. Dissolution studies were promptly conducted to examine the release rate performance of DCN from all binary systems. The drug dissolution properties of binary systems improved significantly in comparison to crystalline DCN. The rate and extent of DCN release were observed to be strongly dependent on the proportion of PXMR present within the formulations.

Preparation and physicochemical characterization of surfactant based solid dispersions of ezetimibe.

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.

Determination of Montelukast Sodium and Bambuterol Hydrochloride in Tablets using RP HPLC.

An accurate, specific and precise assay level gradient reverse-phase high-performance liquid chromatographic method was developed for simultaneous determination of montelukast sodium and bambuterol hydrochloride in tablet dosage form. An inertsil ODS C-18, 5 mum column having 250x4.6 mm I.D. in gradient mode, with mobile phase A, containing 0.025 M sodium phosphate buffer: methanol (85:15) and mobile phase B, containing acetonitrile:methanol (85:15) was used at different time intervals. The flow rate was 1.5 ml/min and effluent was monitored at 218 nm. The retention times of montelukast sodium and bambuterol hydrochloride were 21.2 min and 5.8 min respectively. The linearity for both the drugs was in the range of 0.25-0.75 mg/ml with correlation coefficients of 0.9999 and 0.9996 for montelukast sodium and bambuterol hydrochloride, respectively.

Spectrophotometric estimation of ropinirole hydrochloride in tablets.

A simple, sensitive, rapid, accurate and precise spectrophotometric method has been developed for estimation of ropinirole hydrochloride in bulk and tablet dosage forms. Ropinirole hydrochloride shows maximum absorbance at 250 nm with molar absorptivity of 8.703x10(3) l/mol.cm. Beer's law was obeyed in the concentration range of 5-35 mug/ml. Results of analysis were validated statistically and by recovery studies.

Development and characterization of bicalutamide-poloxamer F68 solid dispersion systems.

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.

Solid-state characterization and dissolution properties of bicalutamide-beta-cyclodextrin inclusion complex.

The solid-state properties and dissolution profile of bicalutamide beta-cyclodextrin (betaCD) inclusion complex were investigated. The phase solubility profile of bicalutamide with beta-cyclodextrin was classified as A(L)-type. Stability constant with 1:1 molar ratio was calculated from the phase solubility diagram and the aqueous solubility of bicalutamide was found to be enhanced by 86% for beta-cyclodextrin. Binary systems of bicalutamide with betaCD were prepared by the kneading method. The solid-state properties of the complex were characterized by differential scanning calorimetry, Fourier transformation-infrared spectroscopy and X-ray powder diffractometry. It could be concluded that bicalutamide could form an inclusion complex with beta-cyclodextrin. The dissolution profile of the inclusion complex was determined and compared with those of bicalutamide alone and its physical mixture. The dissolution rate of bicalutamide was significantly increased bycomplexation with betaCD, as compared with pure drug and physical mixture.

Spectrophotometric estimation of bicalutamide in tablets.

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.