The influence of ultrasound on percutaneous absorption of ketorolac tromethamine was studied in vitro across rat skin. Sonication was carried out with a continuous mode, at an intensity of 1-3 W/cm2 and a frequency of 1 MHz for 30 min. A significant increase in permeation of ketorolac through rat skin was observed with the applied sonication at 3 W/cm2 when compared with permeation at 1 and 2 W/cm2. Enhanced ketorolac penetration at 3 W/cm2 can be explained by the mechanical and/or thermal action of ultrasound waves. The distance of the ultrasound probe from the skin surface did not influence the flux of the drug. Pretreatment of skin by 5% d-limonene in ethanol for 2 hr followed by sonication at 3 W/cm2 (30 min) significantly enhanced the permeation of ketorolac when compared with passive flux with or without enhancer pretreatment.

The effectiveness of the combination of thermosensitive liposomes of plumbagin and hyperthermia is described. Small-sized, thermosensitive liposomes were prepared by thin film hydration and subsequent sonication. The liposomes were characterized for size, phase transition temperature, in vitro drug release and stability. The results of particle size analysis indicated that almost 90% of the vesicles were below 0.19 microm size. The phase transition temperature of the liposomes as determined by differential scanning calorimetry was found to be 41.32 degrees C. The results of in vitro release studies in phosphate buffered saline + mouse plasma indicated that maximum drug release (51.25%) occurred at 42 degrees C compared to the less than 9% release at 37 degrees C. Better stability profile was observed when the plumbagin liposomes were stored at 4 degrees C. When combined with localised hyperthermia (43 degrees C, 30 min or 1 h), liposomal plumbagin administered intravenously to C57BL/6J mice bearing melanoma exhibited better anticancer activity as compared to animals treated with an equivalent dose of free plumbagin with or without hyperthermia, which was evident by enhanced volume doubling time and growth delay.

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In this study, a novel approach for compression of matrix pellets into disintegrating tablets has been studied in an attempt to overcome the issues pertaining to rupture of polymer coat during compression of reservoirtype pellets. Extended release matrix pellets were prepared by the extrusion/spheronization technique using commercially available aqueous dispersions of ethyl cellulose, acrylic polymers and sodium alginate at 10%, 20% and 30%w/w levels. Sertraline hydrochloride was used as the model drug and an in vitro release profile of 12 h was targeted. Tablets containing matrix pellets were prepared by the direct compression process. Acceptance Value, a pharmacopeial test, was applied to study the uniformity of drug distribution. Effect of compression force (2-6 kN), extrusion screen aperture size, diluent blend composition and pellet percentage on drug release and acceptance value were studied. As polymer is uniformly distributed within each pellet, the drug release pattern from uncompressed pellets was comparable to compressed tablets. Surface morphological changes due to calcium chloride treatment were observed using Scanning electron microscopy. The pellet segregated from the surface of the tablet was found to be flattened in the direction of applied compression force with minor deformities. In conclusion, matrix pellets can constitute an alternative approach to reservoir-type pellets in obtaining disintegrating tablets for extended delivery of drugs.Uniterms: Pellets/extended release/evaluation. Pellets/obtention. Pellets/compression. Extrusion/spheronization technique.Nesse trabalho, estudou-se nova abordagem para a compressão de matrizes de péletes em comprimidos desintegrantes, com o intuito de resolver os problemas relativos à ruptura do polímero de revestimento durante a compressão dos péletes do tipo reservatório. Matrizes de péletes de liberação estendida foram preparadas pela técnica de extrusão/esferonização, utilizando dispersões aquosas comercialmente disponíveis de etil celulose, polímeros acrílicos e alginato de sódio a 10%, 20% e 30% p/p. O cloridrato de sertralina foi utilizado como fármaco modelo e focalizou-se no perfil de liberação in vitro de 12 horas. Os comprimidos contendo matrizes de péletes foram preparados pelo processo de compressão direta. O valor de aceitação, teste farmacopéico, foi aplicado para estudar a uniformidade de distribuição do fármaco. O efeito da força de compressão (2-6 kN), o tamanho da abertura de extrusão, a composição da mistura diluente, a porcentagem de pélete na liberação de fármaco e o valor de aceitação foram estudados. Como o polímero é uniformemente distribuído dentro de cada pélete, o padrão de liberação do fármaco dos péletes não-comprimidos foi comparável àquele dos comprimidos. As mudanças morfológicas da superfície devidas ao tratamento com cloreto de cálcio foram observadas utilizandose a microscopia eletrônica de varredura. O pélete segregado da superfície do comprimido mostrou-se plano em direção à força de compressão aplicada com menores defor...

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae0?t were 604.24 ? 348.73 ?g and 627.36 ? 327.99 ?g, while the mean Rmax were 193.87 ? 114.68 ?g/h and 202.00 ? 107.83 ?g/h for the test and reference formulations, respectively. The Tmax of the test and reference tablets were 1.26 ? 0.58 h and 1.26 ? 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae0?t and Rmax of alendronic acid, were between 0.86?1.00 and 0.85?1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.