ABSTRACT
The main objective of this study was to prepare colon-specific pellets of budesonide, using pectin as film coating. Pellet cores of budesonide were prepared by extrusion / spheronization technique. Pectin, in different ratios was combined with Eudragit RS30D, Eudragit NE30D or Surelease to produce film coating. The dissolution profiles of pectin coated pellets were investigated in pH of 1.2 [2 h], pH of 7.4 [4 h] and pH of 6.8 in the absence as well as presence of rat cecal contents [18 h]. Finally the selected formulation was evaluated on trinitrobenzenesulfonic acid [TNBS] induced ulcerative colitis in rat model, in comparison with conventional UC treatments. The dissolution profiles of pectin coated pellets showed that the release of budesonide in presence of rat cecal content depended on adjuvant polymer, the ratio of pectin to polymer and film thickness. Coated pellets, prepared out of pectin and Surelease at a ratio of 1:3 at coating level of 35% [w/w], could increase budesonide release statistically in presence of rat cecal content, while they released no drug in pH of 1.2 and 7.4. Animal experiments revealed the therapeutic efficacy of pectin/Surelease-coated pellets of budesonide in alleviating the conditions of TNBS-induced colitis model as reflected by weight gain, as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis. This confirmed the ability of the optimized formulation for targeted drug delivery of budesonide to colon
ABSTRACT
A sensitive, accurate and rapid reverse phase HPLC method was developed to quantitate plasma levels of metronidazole in order to conduct a comparative bioavailabllity studies. The drug and internal standard were added to plasma samples, vortexed and then zinc sulfate solution was added in order to precipitate the plasma proteins. Samples were centrifuged at 3000 rpm for 10 min. The supernatant layer was separated and analyzed on a phenyl [300 X 4.6mm] column, with 5% acetonitrile in 0.1 M KH [2] PO[4] buffer [pH = 4.5] at 324 nm. The standard curve covering 0.15-30 micro g/ml concentration range, was linear [r [2] = 0.9999], relative errors were within 2.48 to 9.15% and the CV% ranged from 2.999 to 10.796. The method is suitable for bioavailability, pharmacokinetic, and bioequivalent studies in human. The in-vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailabllity was compared using the total area under the plasma level versus time curve [AUC [0-48], AUC [0-infinity], peak plasma concentration [C[max]] and time to [C[max] [T[max]]. No statistically significant difference was found between the AUC [0-infinity], C[max] and T[max] values of the test and reference, Flagyl [R] [p > 0.05]. The 90% CI for the ratio of the AUC [0-infinity], [0.94-1.07] and C[max] [0.88-1.03] and the logarithmically transformed AUC[0-infinity] [0.99-1.01] and C[max] [0.94-1.01] values of the generic product over those of Flagyl [R] was calculated to be within the acceptable limit of 0.80-1.20 and 0.80-1.25, respectively. It was, therefore, concluded that the generic metronidazole was bioequivalent with the innovator formulation