Mohamed A. Etman

Thermodynamics of paracetamol solubility in sugar-water cosolvent systems

Abstract The solubility of paracetamol in different concentrations of sorbitol, glucose and sucrose solutions was studied at 20 and 37°C. There was an appreciable decrease in solubility of the drug at both temperatures, the effect generally being more apparent at the lower temperature as reflected by the solubility ratios. Sorbitol exhibited the greatest effect followed by glucose then sucrose. Thermodynamic parameters were calculated and showed the nonspontaneity of the solubility process (positive free energy values). Entropy changes were positive or of small negative values, while enthalpy changes were positive and of relatively small values. Such results are compatible with the occurrence of hydrophobic interactions that led to a reduction in the solubility of the antipyretic agent. However, the effect of sugar concentration on the thermodynamic parameters was not the same with the three sugars tested, suggesting differences in their solvency characteristics.

Effect of milk and food on the bioavailability of ketoprofen in man

Abstract The influence of milk and of a standard breakfast on ketoprofen bioavailability from commercial capsules was studied in 4 healthy volunteers. The drug was administered as a single oral dose of 50 mg. Evaluation of the absorption rate was done by means of urinary excretion measurements. Eight urine samples were collected over a 24-h period following ketoprofen administration and the drug urine concentrations were determined by HPLC. The data were statistically analyzed by the t -test for paired observations. Milk significantly reduced the extent of ketoprofen absorption, while both the rate and extent of absorption were significantly reduced by food.

Preparation and evaluation of fast-release mephenamic acid microspheres.

Mephenamic acid is characterized by low solubility, which affects its dissolution rate and bioavailability. The objective of this study was to develop fast-release microspheres of ammonium salt of the drug (AMM) by emulsion congealing.The effect of polymer, drug to polymer ratio, surfactant, type and volume of oil phase, stirring rate, microsphere size, encapsulation efficiency and stability of the microspheres were investigated. The results pointed out a good yield (69–98%) and encapsulation efficiency (71–100%). Optimum conditions include moderate molecular weight PEG, inclusion of Tween 20 and/or Span 80, high ratio of PEG (1 : 4, drug : PEG), use of mineral oil and high stirring rate (2000 rpm). Dissolution efficiency ranged between 57% and 90%. Effect of ageing on drug content and release revealed that the microspheres prepared remained stable throughout 1 year of storage. The described method was simple, efficient and resulted in stable microspheres with enhanced drug release.

In vitro adsorption of mepyramine maleate onto some adsorbents and antacids

Abstract The adsorption of mepyramine maleate on bentonite, charcoal, magnesium oxide, magnesium carbonate, magnesium trisilicate, bismuth carbonate and kaolin, was investigated. Maximum adsorption was found with charcoal followed by bentonite while kaolin and bismuth carbonate showed minimum adsorption. The results also showed that as the weight of the adsorbent increases the amount of drug adsorbed per gram decreased. Behaviour of charcoal and bismuth carbonate followed Langmuir and Freundlich isotherms. The present study also revealed that firstly, it is contraindicated to coadministrate mepyramine maleate with the tested adsorbents and antacids; secondly, cetrimide can be added to formulated antidotes for improving their adsorption efficiency.

Simultaneous determination of four hormonal compounds in oral contraceptive tablet formulations by high performance liquid chromatography

ABSTRACT A rapid, accurate, and precise HPLC method has been developed for simultaneous determination of four contraceptive hormonal compounds namely ethinylestradiol (EE), drospirenone (DR), gestodene (GS), and levonorgestrel (LV) in oral contraceptive tablet dosage form. The chromatographic separation was achieved on a C18 (150 × 4.6 mm, 5μ) column; the mobile phase consists of acetonitrile: water (50:50, v/v) pumped at a flow rate of 1.0 mL/min; and UV detection was set at 200 nm. The limit of detection was 0.0086 µg/mL for (EE), 0.0397 µg/mL for (GS), 2.80 µg/mL for (DR), and 0.229 µg/mL for (LV), whereas the limit of quantitation (LOQ) was 0.028 µg/mL for (EE), 0.132 µg/mL for (GS), 9.500 µg/mL for (DR), and 0763 µg/mL for (LV), respectively. The correlation coefficient (r) values of the four compounds ranged from 0.99995 to 0.99999. The method was validated as per ICH guidelines and USP 34 for estimation of (EE), (DR), (GS), and (LV) in commercially available tablet dosage form. The validation results were found satisfactory. The proposed method can be useful in quality control of bulk manufacturing and pharmaceutical dosage forms. GRAPHICAL ABSTRACT

Effect of metoclopramide on ketoprofen pharmacokinetics in man

Abstract The effect of oral administration of metoclopramide (10 mg) on the absorption of ketoprofen from a capsule dosage form (50 mg) was studied in four healthy subjects in a cross-over design. The plasma concentrations of ketoprofen were determined by a HPLC technique. The results demonstrated a marked decrease in drug levels during coadministration with metoclopramide in the first 2 h post-dose. Metoclopramide resulted in markedly lower AUC and C max values with a longer T max of ketoprofen in comparison with the corresponding values for the drug alone. The results suggest that the gastric phase of ketoprofen absorption is the determinant step of the process. Rapid transit of the capsule, due to metoclopramide, reduces the time required for adequate dissolution and absorption.

In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

Objectives: The objectives of this study were to assess the bioavailability of an optimized mephenamic acid (MFA) microspheres (test) against a Ponstan® capsule (reference) in healthy volunteers, and to establish a correlation with in vitro parameters. Subjects andMethods: Four subjects received the test and reference (250 mg MFA each) in a randomized crossover design, separated by a 1-week washout period. The drug was analyzed in plasma by a specific high-performance liquid chromatographic method. The relevant pharmacokinetic parameters [maximum plasma concentration (Cmax), time of peak concentration (Tmax), area under plasma concentration-time curves from 0 to 12 h (AUC0–12) and area under plasma concentration-time curves from zero to ∞ (AUC0–∞)] were calculated from the plasma drug concentration-time data. Results: The test product exhibited faster absorption (Tmax of 1.87 ± 0.482 vs. 2.14 ± 0.20 h; Cmax of 5.91 ± 0.604 vs. 3.58 ± 0.671 µg/ml) when compared to the reference. The relative bioavailability of the test compared to the reference capsule was 172%. Good correlations were established between the in vitro 90% dissolution (T90) and each of the AUC0–12 and Tmax, as well as between the percentage of drug released and plasma concentrations. Conclusion: The formulation of MFA microsphere with polyethylene glycol improved the dissolution rate and bioavailability of MFA, as evidenced by a higher Cmax, AUC0–12 and AUC0–∞, and shorter Tmax values. Good correlations between T90 and both AUC0–12 and Tmax as well as between the percentage of drug released and plasma concentrations were achieved.