methylcellulose and phosphoric-acid

The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7μm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel.

Topics: Administration, Oral; Animals; ATP Binding Cassette Transporter, Subfamily B; Benzopyrans; Biological Availability; Capsules; Drug Carriers; Isoquinolines; Lactose; Male; Mesylates; Methylcellulose; Paclitaxel; Phosphoric Acids; Polymers; Powders; Rats; Rats, Sprague-Dawley; Silicon Dioxide; Solubility; Tetrazoles

The purpose of this study was to compare the effects of experimentally derived surfactant-containing acid gel with those of different surface-conditioning agents on microleakage of unfilled and filled sealants applied to permanent teeth following noninvasive and invasive procedures.. Four main groups of surface-conditioning agents (NRC; NRC + Prime&Bond NT; Email Preparator Blue; and experimental acid gel) were subdivided into 16 subgroups (n = 8). Subgroups were designed according to the surface preparation procedures applied (noninvasive and invasive) and fissure sealants used (Helioseal and Helioseal F). After application of the test materials, the specimens were subjected to thermocycling and then immersed in 0.5% basic fuchsin dye. Following sectioning, specimens were examined under a stereomicroscope and microleakage scores were assigned.. Subgroups 9 (Email Preparator Blue + Helioseal), 11 (invasive + Email Preparator Blue + Helioseal), 13 (experimental acid gel + Helioseal), and 15 (invasive + experimental acid gel + Helioseal) showed no microleakage. The differences between those subgroups and subgroups 1 (NRC + Helioseal), 2 (NRC + Helioseal F), 3 (invasive + NRC + Helioseal), 4 (invasive + NRC + Helioseal F), 5 (NRC + Prime&Bond NT + Helioseal), and 6 (NRC + Prime&Bond NT + Helioseal F) were statistically significant.. Email Preparator Blue and surfactant-containing experimental acid gel, combined with an invasive/noninvasive surface preparation procedure and Helioseal, significantly prevented microleakage.

Topics: Acid Etching, Dental; Analysis of Variance; Composite Resins; Dental Cavity Preparation; Dental Leakage; Gels; Humans; Maleates; Materials Testing; Methylcellulose; Phosphoric Acids; Pit and Fissure Sealants; Polymethacrylic Acids; Polysorbates; Statistics, Nonparametric; Surface-Active Agents