Mutaz S. Salem

Formulation and Release Behavior of Diclofenac Sodium in Compritol 888 Matrix Beads Encapsulated in Alginate

Sustained-release polymer beads containing diclofenac sodium (DNa) dispersed in Compritol 888 and encapsulated in calcium alginate shell were prepared utilizing 23 factorial design. The effect of sodium alginate concentration, drug:Compritol 888 weight ratio and CaCl2 concentration on drug content (%), time for 50% and 80% of the drug to be released, and mean dissolution time (MDT) were evaluated with analysis of variance (ANOVA). An increase in the level of all these factors caused retardation in the release, and t50%, t80%, and MDT were increased. The drug release was dependent on the pH of the release media. A formula that gives a release comparable to commercial products was prepared.

Characterization of famotidine polymorphic forms

Famotidine, crystallized from different solvents and solvent mixtures, was found to exist in three crystal forms, A, B, and C, depending on the solvent system used. This was confirmed by differential scanning calormimetry (DSC), infra-red (IR) spectroscopy, X-ray powder diffraction, thermomicroscopy, scanning electron microscopy and equilibrium solubility. The A, B, and C forms which melt at 171.3°C, 166.4°C and 160.9°C, respectively, were obtained in pure form by crystallization, as indicated from their DSC thermograms. The B form, which is the commercial form of famotidine, is probably the most stable and has therefore the lowest aqueous solubility (0.55 mg/ml). The solubility of the A form (0.82 mg/ml) is comparable to that of the C form (0.85 mg/ml).

Mucoadhesive Dosage form of Lidocaine Hydrochloride: I. Mucoadhesive and Physicochemical Characterization

The aim of this study was to characterize a buccal mucoadhesive film using lidocaine and its hydrochloride salt (LDHCL) as a model drug. Buccal films were developed using carbopol 971P as a mucoadhesive polymer, and glycerol as a plasticizer. Scanning Electron Microscope, Differential Scanning Calorimetry, X-ray powder diffraction, and Fourier Transform Infra Red techniques were used to characterize the mucoadhesive films. Bioadhesive properties were evaluated using the Universal Instron Instrument with chicken pouch as a model tissue. LDHCL and its base were present in carbopol 971P films in a molecular dispersion state without exerting any effect on the glass transition of these films. The mucoadhesive force between the chicken pouches and the film containing glycerol did not change by time during the tested period (1–20 min), while increased with increasing the amount of glycerol (10–40% w/w of polymer content). Furthermore, a linear increase in the mucoadhesive force was accompanied by the increase in the film thickness, while a linear decrease followed by plateau was obtained when loading the patch with LDHCL at concentration above 1 mg/cm2. Loading carbopol film with lidocaine base, in a concentration up to 6 mg/cm2 decreased linearly the mucoadhesive properties, which could be attributed to salt formation between the acidic carboxylic moiety of carbopol and basic lidocaine.

Potential mucoadhesive dosage form of lidocaine hydrochloride: II. In vitro and in vivo evaluation.

ABSTRACT The aim of this study was to develop a controlled release buccal mucoadhesive delivery system for systemic delivery of lidocaine hydrochloride as a model drug. In vitro release and buccal permeation as well as in vivo permeation of LDHCL patches were evaluated. The drug release and the permeability of the drug through porcine buccal mucosa were evaluated using Franz diffusion cell. In vivo evaluation of patches was carried out on rabbits as an animal model. Patches were designed in two fashions, bi-layer (BLP; LDHCL, carbopol, glycerin, pentration enhancer, and Tween 20 as the first layer; and EVA as the second layer) and triple layer (TLP; LDHCL, carbopol and glycerin as the first layer; carbopol, glycerin, pentration enhancer and pluronic F-127 as the middle layer; and EVA as the third layer) patches, respectively. Presence of oleic acid as PE in the formulation significantly enhanced the in vitro permeability of LDHCL (p < 0.05), while propylene glycol monolaurate as PE suppressed it (p < 0.05). The in vivo evaluation in rabbits showed that TLP had significantly higher Cmax and AUC0–8 (p < 0.05) than BLP. Furthermore, TLP showed a well-controlled drug plasma concentration over 6 hr which was significantly longer than BLP (p < 0.05). Patches were well adhered to buccal mucosa of the rabbits over the 8-hr study period. It was postulated that the hypothetical release mechanism of the drug and oleic acid from TLP was controlled by their diffusion through the swollen polymer network and micelled gel.

High-performance liquid chromatographic determination of methotrexate in plasma

A procedure for the determination of methotrexate in human plasma is reported. The analysis involved extraction of methotrexate as an ion pair in ethyl acetate. Reconstituted residue was analyzed using reverse phase C-18 column and a mobile phase consisting of acetate buffer (87%), methanol (6.5%), and acetonitrile (6.5%). The methotrexate recovery range was 95–97%. Theophylline was used as internal standard with a recovery of 96%. The intraday coefficient of variation for the assay ranged from 1.8–3.0%, while interday variation coefficient range was 3.5–3.7%. The method is selective, reproducible, and covers a wide range of methotrexate concentrations in patients plasma.

High Pressure Liquid Chromatographic Analysis of Orphenadrine Citrate and Acetaminophen in Pharmaceutical Dosage Forms

Abstract An ion pair reversed phase high pressure liquid chromatographic method for the analysis of orphenadrine citrate (I) and acetaminophen (II) was developed. The mobile phase consisted of 20mM sodium-1-octane sulfonate in 50mM phosphate buffer (pH=3.0), mixed with 22.5% organic solvents (50:50, acetonitrile: methanol). The method is simple, reliable and could be adapted for quality control purposes.

Determination of factors affecting kinetics of solid-state transformation of fluconazole polymorph II to polymorph I using diffuse reflectance Fourier transform spectroscopy

Background: It was of interest to investigate the factors affecting kinetics of transformation of fluconazole polymorph II (the metastable form) to fluconazole polymorph I (the stable form) using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Method: Fluconazole polymorphs I and II both were prepared by crystallization in dichloromethane. The two forms were characterized using differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, solubility, and DRIFTS. Transformation of polymorph II to polymorph I was also studied under different isothermal temperatures using DRIFTS. Kinetic analyses of the data were done using model-dependent and model-independent methods. Eighteen solid-state reaction models were used to interpret the experimental results. Results: Based on statistics, the Prout–Tompkins model provided the best fit for the transformation. The activation energy (Ea) value derived from the rate constants of the Prout–Tompkins model was 329 kJ/mol. Model-independent analysis was also applied to the experimental results. The average values calculated using both methods were not significantly different. Factors affecting kinetics of transformation such as mechanical factors, relative humidity, and the effect of seeding were also studied. Mechanical factors, which included trituration and compression, proved to enhance transformation rate significantly. Relative humidity proved to transform both polymorphs to monohydrate form. The presence of seed crystals of polymorph I was proved not to affect the transformation process of polymorph II to polymorph I. Effect of solvent of crystallization (dichloromethane) was studied. A significant change of the rate of transformation was proved in the presence of solvent vapors, and a change on the mechanism was proposed.

High Pressure Liquid Chromatographic Analysis and Dissolution of Famotidine in Tablet Formulation

Abstract A reversed phase high pressure liquid chromatographic method was developed for the quantitation of famotidine in tablet formulation using a mobile phase consisting of 0.1M phosphate buffer (84%), acetonitrile (11%) and methanol (5%) at a pH of 6.5. The detection wavelength was set at 285 nm. The method is precise and adaptable for quality control purposes. The use of the analytical method hi studying tablet dissolution is described.

Evaluation of Hydroxyethyl Esters of Mefenamic Acid and Diclofenac as Prodrugs

AbstractHydroxyethyl esters of diclofenac and mefenamic acid were prepared with the aim of obtaining enzymatically labile prodrugs, and their stability was evaluated in aqueous buffer solutions of pH 7.4, 1 N HCl, and also in human plasma. The hydrolytic degradation of diclofenac ester in aqueous buffer solutions was slow, as shown by t1/2 values greater than 22 hr, while rapid enzymatic hydrolysis occurred in the plasma (t1/2 = 1.12 hr). However, the mefenamic acid ester showed a relatively higher stability in buffer solutions (t1/2 greater than 38 hr at pH 10) as well as in the plasma (t1/2 = 7.28 hr) compared with the diclofenac ester. Therefore, the mefenamic acid ester would not be considered suitable as a prodrug.

Determination of the mechanism of uptake of organic vapors by chitoasn.

It was of interest to investigate the possible interactions that might occur between chitosan and various compounds of different polarities using solvent vapor sorption and Fourier Transform Infrared Spectroscopy (FTIR). The sorption system was composed of a gas inlet, a 2 meter gas cell and a gas outlet. The experimental set up allowed quantification of the free vapor and therefore the amount of the sorbed vapor by chitosan powder. The BET equation was applied to the experimental data to obtain the apparent monolayer sorption capacity (Sm) and the parameter C, which is related to the heat of interaction. Results demonstrated that the surface areas obtained for chitosan from the BET analyses for heptane, 1,4-dioxane and methanol were 421, 379 and 58 m2/g, respectively. These values were extremely higher than the value obtained from nitrogen vapor adsorption isotherm (4.56 m2/g). The difference is attributed to the partitioning of these compounds into the chitosan particles. The large difference in the Sm values between the nonpolar (heptane and 1,4-dioxane) and the semipolar compounds (methanol) also suggested that the polarity of the solvent might have a significant effect on the partitioning of the these compounds into the chitosan particles. The results obtained from this study also confirmed what was previously described regarding the ability of chitosan to act as a ‘fat magnet’ or a ‘fat sponge’.