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

Comparative bioavailability of norfloxacin tablets based on blood and urine data

To assess the bioavailability of norfloxacin from urinary excretion relative to plasma concentration. Twelve healthy volunteers [22-33 years] participated in the study. Each received a previously developed [M], a local [L] and a multinational [Noroxin] tablet [Ref], 400 mg each, according to a random balanced three-way crossover design on 3 different days. Blood samples were collected over a 12-hour period and urine over a 24-hour period. Norfloxacin concentrations were analyzed by a validated HPLC method. An initial estimate of bioequivalence of the three products was obtained using analysis of variance on transformed data and based on confidence interval calculation. Elimination pharmacokinetic parameters [half-life and renal clearance] calculated from plasma concentration and urinary excretion data [mean values, n = 36] were comparable to reported values for norfloxacin. Interproduct differences in elimination parameters [mean values, n = 12] were statistically insignificant [F values, ANOVA]. Strong association was found between the mean of plasma concentration and urinary excretion rates for many volunteers [F values, regression analysis]. Relative bioavailability values calculated for the local and previously developed products relative to Noroxin were higher than 85% based on area under the curve and urinary excretion. Bioequivalence could not be established among the three tested products based on calculated 90% confidence intervals. Urinary excretion of norfloxacin may be a useful noninvasive tool for bioavailability assessment of norfloxacin oral formulations

Formulation and stability of directly compressed ibuprofen tablets

Different formulations of ibuprofen tablets were prepared by direct compression at 8 to 24 kN, employing lactose and dicalcium phosphate [Di-Cafos] as direct compressible vehicles [DCV]. For enhancing drug dissolution, hydrophilic materials, partially hydrolyzed gelatin [PHG], polyvinyl pyrrolidine [PVP] and urea were utilized in the formulations as simple and as ball-mill ground mixtures with the drug [1: 1]. The tablets were tested after manufacture and during storage, at room temperature [RT] and at 40C or dissolution, disintegration time [DT], friability, hardness and drug content. Stability of ibuprofen in the different formulations were determined using a newly developed stability-indicating method HPLC. The fresh tablets fulfilled the USP XXIII specifications of dissolution for urea as a simple mixture. The dissolution of tablets stored at RT conformed with the pharmacopoeial limits, except gelatin/Di-Cafos tablets. At 40C, only PVP/lactose tablets failed the dissolution test. The hardness of the freshly prepared tablets exhibited the highest hardness values in addition to maximum sensitivity towards increase of compression force [8-24 kN], yet with longer DT

Evaluation of ball-mill ground mixtures of hydrophilic carriers and phenytoin

Phenytoin [P] powder was ground with several hydrophilic carriers; namely, avicel, lactose, gelatin, partially hydrolyzed gelatin and urea, using a ball-mill to enhance drug dissolution. The effect of mechanical treatment on the physicochemical properties of P was investigated by scanning calorimetry microscopy [SEM], different scanning calorimetry [DSC], infrared spectroscopy [IR] and X-ray diffractometry [X-ray]. Simple and ground mixtures of P with each carrier [in 1:1 and 1:4 ratios] were prepared. Dissolution of P and the different mixtures in 1% sodium lauryl sulfate [SLS] was found to be non-discriminative. When water was used as the dissolution medium, instead of 1% SLS, the ground mixtures exhibited higher dissolution rates. The effect of the carriers in this respect could be arranged as follows: Lactose > urea > avicel > gelatin. Grinding of P with lactose to less extent with other carriers resulted in the loss of DSC-peak symmetry of P. The defined IR absorption b and s in the fingerprint region of P were also obliterated to variable extents by the various carriers, especially with lactose. The results suggested the possibility of P-carrier interactions with higher tendency in case of lactose, through H-bond and van der Waals forces