In vitro/in vivo correlation of fast release mephenamic acid microspheres in humans

The objectives of this study were to assess the bioavailability of an optimized mephenamic acid [MFA] microspheres [test] against a Ponstan[R] capsule [reference] in healthy volunteers, and to establish a correlation with in vitro parameters. 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 [C[max]], time of peak concentration [T[max]], area under plasma concentration-time curves from 0 to 12 h [AUC[0-12]] and area under plasma concentration-time curves from zero to infinity [AUC[0-infinity]] were calculated from the plasma drug concentration-time data. The test product exhibited faster absorption [T[max] of 1.87 +/- 0.482 vs. 2.14 +/- 0.20 h; C[max] of 5.91 +/- 0.604 vs. 3.58 +/- 0.671 micro g/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 AUC[0-12] and T[max], as well as between the percentage of drug released and plasma concentrations. The formulation of MFA microsphere with polyethylene glycol improved the dissolution rate and bioavailability of MFA, as evidenced by a higher C[max], AUC[0-12] and AUC[0-infinity], and shorter T[max] values. Good correlations between T90 and both AUC[0-12] and T[max] as well as between the percentage of drug released and plasma concentrations were achieved

Dissolution rate enhancement of sparingly soluble drugs by surface adsorption of surfactants

A simple reproducible method of the dissolution rate enhancement by surface adsorption of surfactants onto surfaces of sparingly water soluble drugs was described. It is more economic, applied for any hydrophobic drug, no organic solvent is required for preparing the drug crystals, the necessity of the solubility of the drug is solvent. Some factors affecting the adsorption characteristics of the surfactants on the tested drugs, such as types of surfactants, on the tested drugs such as types of surfactants, effect of temperature and effect of solvent composition during preparing of drug crystals were investigated. Washing of the treated samples was also investigated to study its effect on the dissolution behavior of the prepared crystals. The dissolution rate behavior of the non-treated commercial drugs was studied in 0.1% aqueous surfactant solutions and compared with the results obtained of treated samples prepared by different methods. The obtained results revealed that all the surfactant treated crystals gave an enhancement of the dissolution rate. It was considered that the method of preparation to the crystals might be partially responsible for the observed behavior

In-vitro uptake of xanthine bases by charcoal A preliminary approach to the adsorption rate study

Xanthine bases were found to be adsorbed on charcoal at a varying degree. The adsorption of these bases may be attributed mainly to the hydrophobic interaction forces. Theophylline was found to be adsorbed more than caffeine onto charcoal. Theophylline and theobromine were found to be adsorbed from acidic medium more than caffieine which was found to be more adsorbed in alkaline solution than the other two xanthines. The amount of the drug adsorbed onto charcoal was found to be influenced by temperature, concentrations of either xanthines or charcoal and the dielectric constant of the solvent used. The solubility and viscosity determinations of the drugs in ethanol-water systems of different dielectric constants have been carried out and were found to be affected by the solvent compositions. Parallel correlations were observed between the results of both solubility and viscosity. Minimum adsorption of the tested drugs was occurred from solvent gave either maximum solubility or maximum viscosity. In general, the higher the dielectric constant of the medium, the higher would be the amount of the drug adsorbed and the lower of both solubility and viscosity. It was observed that, for each xanthine bases, there was certain dielectric constant value where minimum adsorption was occurred and any deviation around this value will increase the amount of the base adsorbed. This behavior may be attributed to the maximum solute-solvent interaction at this attributed to the maximum solute-solvent interaction at this value or may be due to the high viscosity of the medium at this value

Nitrofurantoin II Correlation of in vivo bioavailability to in vitro dissolution of nitrofurantoin tablets aged at different relative humidities and elevated temperatures

The results of the present study on the stored nitrofurantoin tablets by measuring the amount of unchanged drug excreted in the urine of seven subjects revealed that there is a best in vivo and in vitro correlation. The various in vivo values considered included the mean cumulative amounts excreted at different times, the mean amount excreted at the peak time [mg], and the peak time [hr]. The in vitro values tested included time for a give percentage of the drug to be dissolved, the dissolution rate constant, and the t50%. Tablets which have been stored at 100% relative humidity gave the least amount of unchanged nitrofurantoin excreted in the urine. Subjects administered nitrofurantoin tablets of other treatment conditions, gave the same patterns in decreasing the amount of drug excreted in urine, but to a lesser degree compared to the controlled tablets. This investigation suggests that the in vitro drug release can be employed to predict the absorption characteristics of nitrofurantoin tablets which possesses dissolution rate-limited absorption mechanism