Preparation and evaluation of furosemide containing orally disintegrating tablets by direct compression.

The purpose of this research was to develop and prepare orally disintegrating tablets (ODTs) containing furosemide by direct compression method. Furosemide, microcrystalline cellulose (MCC), low-substituted hydroxypropylcellulose LH-11 (L-HPC), aspartame, sodium stearyl fumarate were used for ODT formulation. MCC and L-HPC were used in ratios of 1:9 (ODT1) and 1:4 (ODT2). The results of the quality control parameters obtained for bulk powders (angle of repose, compressibility index, Hausner ratio, bulk density and volume, apparent density and volume, swelling of superdisintegrants and powder moisture) were taken as an indication of good compressibility of tablets. Both ODT1 and ODT2 disintegrated within 15 s and fulfilled the required disintegration time given by the European Pharmacopoeia (3 min). The average weight variation was less than 5% for both tablets. The friability of the tablets was less than 1%. Wetting time of both tablets was in the range of 12-21.7 s. Water absorption ratio was 1.41±0.03 for ODT1 and 1.96±0.10 for ODT2. Dissolution studies revealed that more than 85% of furosemide was dissolved in 15 min from both ODTs. Based on cell culture studies, permeability of furosemide was low (Papp=1x10-5 cm/s) but increased when prepared in the ODT form (ODT1: Papp=2x10-5 cm/s; ODT2: Papp=3.6x10-5 cm/s). Collectively, all these results showed that ODT formulations of furosemide were developed successfully. To improve patient compliance, ODT approach can be suggested for development and manufacturing of furosemide ODTs.

Hepatic disposition of trimethoprim and sulfamethoxazole.

Hepatic disposition of trimethoprim (TMP) and sulfamethoxazole (SMX) and the liver distributional volumes were investigated in the in situ perfused rat liver preparation. Perfusion experiments were conducted using Krebs-bicarbonate buffer delivered via the portal vein (15 ml/min) in a single-pass mode. Erythrocytes (intravascular marker) and Evans blue (extracellular marker) were used for the estimation of liver distributional volumes, and desiccation and freeze-drying methods were used for the estimation of liver water content. TMP and SMX were administered together as a bolus in the presence (1%) and absence of protein. Although SMX profiles displayed a characteristic sharp peak followed by a slower eluting tail in all cases, TMP profiles were dependent on protein; in the absence of protein, the early sharp peak was replaced by a flatter profile with a later peak. Fractional effluent recovery (F; 0.77 vs. 0.82) and hepatic clearance (CL(H); 3.44 vs. 2.70 ml/min) for TMP were not influenced by albumin; with SMX, F increased (0.32 vs. 0.60) and CL(H) decreased (10.2 vs. 6.0 ml/min) with an increase in the perfusate protein concentration. Hepatic extraction of TMP was low (<0.30), whereas it was intermediate (<0.70) for SMX. In addition, distributional volumes and total water content of the liver were successfully determined.

Potential use of freeze-drying technique for estimation of tissue water content.

Desiccation and freeze-drying methods were used for the estimation of water content of various rat tissues. In the desiccation method, the tissue samples were cut into small pieces and subsequently dried at 40 degrees C to constant weight. In the freeze-drying method, the prefrozen tissue samples were freeze-dried (-50 degrees C) for 24 h. Tissue water contents obtained by the desiccation and freeze-drying methods were very similar, with no significant difference between them. Regardless of the method, the highest tissue water content was found in testes (0.841 +/- 0.010 ml/g for freeze-drying and 0.865 +/- 0.002 ml/g for desiccation); the lowest values were obtained in bone (0.254 +/- 0.007 ml/g for freeze-drying and 0.267 +/- 0.003 ml/g for desiccation). Upon correction for the water content of residual tissue blood, regardless of the drying method, significant differences were found between corrected and uncorrected tissue water values of all tissues. However, for a given method, the difference between the tissue water contents was not significant after correcting for residual blood. The water content values for all tissues (except bone) agree well with those published previously and obtained by desiccation. All these clearly suggest that the freeze-drying method can be used as an alternative to desiccation for estimation of tissue water content.