Biodegradable hydrophilic gelatin microspheres containing the anticancer drug methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20 microns) were prepared by polymer dispersion technique and crosslinked with glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of free-flowing powder. About 80 per cent of MTX was incorporated in gelatin microspheres of different sizes. The in vitro release of MTX was investigated in two different media, namely simulated gastric and intestinal fluids. The release profiles indicated that gelatin microspheres released MTX in a zero-order fashion for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal fluid. The rate of release of MTX decreased with increase in the particle size of the microspheres. MTX release was faster in gastric fluid when compared to intestinal fluid.

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This study evaluated the accuracy of esophageal biopsy for the diagnosis of nonerosive reflux disease (NERD) in adults. Thirty-five patients with reflux symptoms and a normal endoscopy were prospectively evaluated using esophageal biopsies, 24-h ambulatory pH monitoring and symptomatic response 4 weeks after an increase in antireflux therapy. Biopsies were scored for the total number of typical histologic reflux features seen. Patients were considered to have NERD if both pH-metry was positive and step-up therapy was successful. Biopsies were then compared to this predefined gold standard. Biopsy was most sensitive (62%) but poorly specific (27%) when one or more histologic reflux features were seen. A threshold of three or more histologic features improved the specificity (91%) but reduced sensitivity (31%). Response to step-up therapy was associated with 100% sensitivity and 100% negative predictive value when compared to biopsy and pH-metry as an alternate combined gold standard. In conclusion, biopsy is insensitive in diagnosing NERD but reasonably specific if three or more typical histologic reflux features are present.

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SYNOPSISMultiple unit delivery dosage forms of biodegradable gelatin microspheres containing the anticancer drug methotrexate (GMM) of various mean particle sizes (1-5, 5-10, and 15-20 pm) were prepared by t h e polymer dispersion technique and were crosslinked with glutaraldehyde. The GMM were coated with biodegradable natural polymers, namely alginate (AGMM) and chitosan (CGMM), which differ in their pH sensitivity, to obtain two different types of pH dependent delivery systems for oral delivery of methotrexate (MTX). The in vitro release profiles of MTX from AGMM and CGMM were determined in simulated gastric medium, intestinal medium, and in media simulating gastrointestinal tract conditions. The effect of the concentration of coating polymer and particle size on the release rate of MTX from both AGMM and CGMM were also studied. Both AGMM and CGMM provided controlled release of MTX following a zero-order release pattern in gastric and intestinal fluids for prolonged periods of time. The release rate of MTX decreased with an increase in concentration of the coating polymer as well as an increase in particle size of the microspheres. Both AGMM and CGMM showed good potential as pH dependent multiple unit delivery systems for the controlled release of MTX in oral administration.