Mohammad S. Suleiman

Improvement of the in vitro dissolution characteristics of famotidine by inclusion in β-cyclodextrin

Abstract An inclusion complex between famotidine and β-cyclodextrin was prepared by mixing the two components in a millimolar ratio in distilled water and heating under reflux for l h followed by stirring at room temperature for 5 days. Phase-solubility studies revealed the formation of a 1:1 complex of the AL type with a rate constant of 74.96 M−1. The formation of the complex in the solid state was confirmed by infrared spectroscopy and differential scanning calorimetry. The inclusion complex was shown by X-ray powder diffraction to be significantly less crystalline than any of the pure components. More significantly, the dissolution rate of the complex from constant surface-area discs was determined to be about twice and six times higher than that of the physical mixture and the pure drug, respectively.

A rapid and sensitive high-performance liquid chromatographic method for the determination of diclofenac sodium in serum and its use in pharmacokinetic studies

Abstract— A rapid, and sensitive high‐performance liquid chromatographic method has been developed for the determination of diclofenac sodium in serum using flufenamic acid as the internal standard. Serum protein was precipitated with acetonitrile. The drugs were eluted from a 5 μm C‐8 reversed‐phase column at ambient temperature with a mobile phase consisting of acetonitrile‐water (50:50% v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL min−1 with UV detection at 280 nm. Each analysis required no longer than 10 min. Quantitation was achieved by the measurement of the peak‐height ratio and the relative and absolute recoveries varied from 90 to 98%. Detection limits for diclofenac sodium in serum is 25 ng mL−1. Intraday coefficients of variation (CV) ranged from 2.47 to 4.61 % and interday CVs from 3.52 to 7% at three different concentrations. Preliminary stability tests showed that diclofenac sodium is stable for at least 2 weeks in serum after freezing. The method is applied for the determination of the pharmacokinetic parameters of diclofenac after administration of two formulations (enteric‐coated tablet and slow‐release tablet), to a healthy male volunteer.

Characterization of a diflunisal polyethylene glycol solid dispersion system

Abstract This work involves the study of the nature of a possible interaction of diflunisal and polyethylene glylol (PEG) in solution and the solid state. Dynamic and equilibrium solubility studies, solvent power calculation and heat of solution determination were used to elucidate the mechanism of interaction in solution. Differential scanning calorimetric studies, infrared spectroscopy and hot stage microscopy were used to elucidate the mechanism of interaction in the solid state. From these studies it was concluded that no chemical interaction takes place between diflunisal and PEG neither in solution nor in the solid state. The increased solubility of diflunisal when dispersed in PEG could be attributed to one or more of several factors such as local solubilization action, reduction in particle size of the drug, alteration of the surface characteristics of the drug particles, increased thermodynamic activity and the high affinity of the drug to the polymer solution.

Isolation and physicochemical characterization of solid forms of glibenclamide

Abstract Two polymorphs and two pseudo-polymorphs of glibenclamide were obtained by crystallization from a number of solvents. They were characterized by thermal microscopy, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, infrared spectroscopy, and dynamic and equilibrium solubility studies. Substantial differences were detected between the polymorphs and pseudo-polymorphs. Particularly, the pentanol and toluene solvates were significantly different with regard to dissolution rate and equilibrium solubility from each other and from the two polymorphs.

Characterization of glibenclamide glassy state

Abstract Glibenclamide crystals were converted to the glassy state by cooling the melt on an ice bath. The glass state formation was confirmed by differential scanning calorimetry (DSC) measurements. Further evidence was provided by other techniques such as infrared spectroscopy (IR), X-ray powder diffraction, equilibrium solubility and dissolution studies. X-ray diffraction patterns of pulverized glassy glibenclamide stored up to 4 months at room temperature indicated no transformation to the crystalline state. The IR studies showed that the characteristic peaks of glibenclamide at 3310, 3100, 1725 and 1610 cm −1 decreased in intensity in the glassy state which was attributed to the partial transformation of the most stable keto form to the enol form during glass formation. storing glassy glibenclamide at different temperatures resulted in a decrease in its equilibrium solubility. This decrease was attributed to the partial transformation of the glassy form to a crystalline form. The kinetics of the transformation process were pseudo first order in nature. Dissolution studies showed that glassy glibenclamide exhibits a higher dissolution rate than either crystalline glibenclamide or a commercially available product (Daonil).

A RAPID HIGH‐PERFORMANCE LIQUID CHROMATOGRAPHY ASSAY OF GLIBENCLAMIDE IN SERUM

A rapid high‐performance liquid chromatography (HPLC) determination of glibenclamide in human serum is described. Serum samples to which flufenamic acid had been added as internal standard were treated with aceto‐nitrile as a protein precipitant. After centrifugation, separation and recon‐stitution, the redissolved residue was eluted from 5 μ Spherisorb C‐8 reversed phase column at ambient temperature using a mobile phase consisting of acetonitrile‐water (45: 55 v/v) at pH 3·7‐3·8 and pumped at a flow rate 2 ml/min. The effluent was monitored at 230 nm. The analysis time was no longer than 12min. A linear relationship between the peak height ratio (glibenclamide/flufenamic acid) and concentration was obtained in the range 20–400 ng/ml. A typical calibration curve has a regression equation y= 0·0035x + 0·015 (r = 0·9999). The detection limit of glibenclamide in serum was 20 ng/ml. The mean recovery of drug from serum samples spiked with known amounts of glibenclamide was 96·77%. Within‐day and between‐day coefficients of variation were 1·6‐4·0% and 1·4‐3·5%, respectively. Stability testing indicated that glibenclamide was stable for at least 10 days in serum — 20°C. The method developed was applied to determine some pharmacokinetic parameters after the oral administration of 5 mg glibenclamide tablets to a human volunteer.

IN VITRO AND IN VIVO EVALUATION OF SUSTAINED-RELEASE AND ENTERIC-COATED MICROCAPSULES OF DICLOFENAC SODIUM

AbstractThis work examines the release of diclofenac sodium from ethylcellulose (EC) microcapsules made up of different drug to polymer ratios. The release process was found to follow the Higuchi square root equation and not the zero-order or first order equations. However, for drug to polymer ratio of 1:1, a critical time (θ) was reached beyond which the release rate was lower than that predicted on the basis of the Higuchi square root equation. Dissolution experiments in 0.1N HCL revealed that less than 1.5% of the encapsulated drug was released in 6 h. This finding indicates the suitability of the EC microcapsules for enteric-coated preparations. The in vitro release of diclofenac sodium from microcapsules of different drug to polymer ratios was compared with that from a commercial sustained-release product. A distinct similarity between the release profile of the commercial product with that obtained for the 1:2 drug to polymer microcapsules was noted. The in vivo work included determination of the se...

A Stability-Indicating Hplc Analysis of Famotidine and Its Application to Kinetic Studies

Abstract A stability-indicating HPLC analytical method has been developed for the determination of the H2-receptor antagonist, famotidine in the presence of its degradation products. the method utilizes reversed phase chromatography with UV detection and internal calibration techniques. the mobile phase was comprised of 84% ammonium acetate buffer (pH 2.9) and 16% acetonitrile and pumped at a flow rate of 1.5 ml/min. Quantitation was performed by measuring the peak height ratio of drug to internal standard (salicylic acid). the limit of famotidine detection was determined to be 10 ng (0.4 ug/ml) with a signal to noise ratio of 3:1. Within day coefficient of variation of the method was 2.22% (2.5 μg/ml) and 0.82% (10 μg/ml). Between day coefficient of variation based on the slopes of daily prepared standard curves was 4.70%. the developed method was used to determine the drug content of famotidine tablets. Further, it was used to investigate the kinetics of degradation of the drug in an acidic solution.

Kinetics of the acid-catalyzed hydrolysis of famotidine

Abstract The kinetics of hydrolysis of famotidine were studied in 0.01–0.10 M hydrochloric acid solutions of 2 mg/ml using a stability-indicating high-performance liquid Chromatographic assay with ultraviolet detection. The hydrolysis followed pseudo-first order kinetics with respect to famotidine concentration. The observed rate constant was found to depend on hydrogen ion concentration and was not influenced by the ionic strength. The specific hydrogen ion catalytic rate constant was calculated to be 3.427 M −1 · h −1 at 37° C. The temperature dependence of famotidine hydrolysis was investigated in 0.1 M hydrochloric acid solutions having an ionic strength of 0.2 in the temperature range 37–55° C. The activation energy was determined to be 63.7 kJ/mol. The impact of the acid-catalyzed hydrolysis on the stability of famotidine in the stomach was discussed. It was estimated that in the gastric pH 1–2 and with a gastric emptying half-life of 50 min in normal young adults about 5.3–35.8% of an oral dose of famotidme would undergo degradation in the stomach. This percentage might be even increased to 12.0–57.8% in the elderly.

Stability-indicating high-performance liquid chromatographic assay for the determination of metoclopramide hydrochloride in pharmaceutical dosage forms

A simple, reliable and selective high-performance liquid chromatographic method for the determination of metoclopramide hydrochloride in pharmaceutical dosage forms has been developed and evaluated. The drug and the internal standard (phenobarbitone) were eluted from a 5-micron C8 reversed-phase column at ambient temperature with a mobile phase consisting of phosphate buffer (10 mM)-methanol-acetonitrile (50 + 28 + 22) adjusted to pH 4.8 with orthophosphoric acid. The mobile phase was pumped at a flow-rate of 1.5 ml min-1 and the effluent was monitored spectrophotometrically at 214 nm. The retention times of the internal standard and metoclopramide hydrochloride were 3.0 and 7.5 min, respectively. Quantification was achieved by measuring the peak-height ratio of the drug to the internal standard. A linear relationship was found over the range 1-10 micrograms ml-1. Within-day coefficients of variation (CVs) ranged from 0.50 to 1.70% and between-day CVs from 0.68 to 4.07% at three different concentrations. The developed procedure was compared with the current BP method for the assay of metoclopramide hydrochloride in tablets. The proposed method was also used to study the stability of metoclopramide hydrochloride.