Sferični kristali celekoksiba za poboljšanje topljivosti, oslobađanja i mikromeričnih svojstava

Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3), with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and in vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal possesses a good spherical shape with smooth and regular surface.U radu je opisana priprava sferičnih aglomerata sa celekoksibom koristeći polivinilpirolidon (PVP), aceton, vodu i kloroform. Aglomerati su karakterizirani diferencijalnom pretražnom kalorimetrijom (DSC), rentgenskom difrakcijom (XRD), IR spektroskopijom i pretražnom elektronskom mikroskopijom (SEM). IR i DSC su pokazale odsutnost bilo kakvih interakcija između ljekovite tvari i aditiva. XRD je pokazala smanjenje kristaliničnosti u aglomeratima. Aglomerati su pokazali značajno poboljšana mikromerična svojstva u odnosu na čisti lijek. Udio lijeka u njima bio je između 93.89 ± 2.26 i 97.32 ± 1.29%. Topljivost u vodi i oslobađanje ljekovite tvari iz aglomerata povećalo se skoro dva puta. Topljivost i in vitro oslobađanje se povećava s povećanjem koncentracije PVP (od 2,5 do 10%). SEM studije su pokazale da kristali imaju pravilan sferični oblik te glatku i pravilnu površinu

Sferični kristali celekoksiba za poboljšanje topljivosti, oslobađanja i mikromeričnih svojstava

Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3), with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and in vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal possesses a good spherical shape with smooth and regular surface.U radu je opisana priprava sferičnih aglomerata sa celekoksibom koristeći polivinilpirolidon (PVP), aceton, vodu i kloroform. Aglomerati su karakterizirani diferencijalnom pretražnom kalorimetrijom (DSC), rentgenskom difrakcijom (XRD), IR spektroskopijom i pretražnom elektronskom mikroskopijom (SEM). IR i DSC su pokazale odsutnost bilo kakvih interakcija između ljekovite tvari i aditiva. XRD je pokazala smanjenje kristaliničnosti u aglomeratima. Aglomerati su pokazali značajno poboljšana mikromerična svojstva u odnosu na čisti lijek. Udio lijeka u njima bio je između 93.89 ± 2.26 i 97.32 ± 1.29%. Topljivost u vodi i oslobađanje ljekovite tvari iz aglomerata povećalo se skoro dva puta. Topljivost i in vitro oslobađanje se povećava s povećanjem koncentracije PVP (od 2,5 do 10%). SEM studije su pokazale da kristali imaju pravilan sferični oblik te glatku i pravilnu površinu

Influence of peptide dendrimers and sonophoresis on the transdermal delivery of ketoprofen

The aim of this study was to determine the individual and combined effects of peptide dendrimers and low frequency ultrasound on the transdermal permeation of ketoprofen. Arginine terminated peptide dendrimers of varying charges (4(+), 8(+) and 16(+), named as A4. A8 and A16 respectively) were synthesized and characterized. Ketoprofen was subjected to passive, peptide dendrimer-assisted and sonophoretic permeation studies (with and without dendrimer application) across Swiss albino mouse skin, both in vitro and in vivo. The studies revealed that the synthesized peptide dendrimers considerably increased the transdermal permeation of ketoprofen and displayed enhancement ratios of up to 3.25 (with A16 dendrimer), compared to passive diffusion of drug alone in vitro. Moreover, the combination of peptide dendrimer treatment and ultrasound application worked in synergy and gave enhancement ratios of up to 1369.15 (with ketoprofen-A16 dendrimer complex). In vivo studies demonstrated that dendrimer and ultrasound-assisted permeation of drug achieved much higher plasma concentration of drug, compared to passive diffusion. Comparison of transdermal and oral absorption studies revealed that transdermal administration of ketoprofen with A8 dendrimer showed comparable absorption and plasma drug levels with oral route. The excised mouse skin after in vivo permeation study with dendrimers and ultrasound did not show major toxic reactions. This study demonstrates that arginine terminated peptide dendrimers combined with sonophoresis can effectively improve the transdermal permeation of ketoprofen. (C) 2017 Elsevier B.V. All rights reserved

Peptide dendrimer-conjugates of ketoprofen: synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery

The aim of this study was to evaluate skin delivery of ketoprofen when covalently tethered to mildly cationic (2or 4) peptide dendrimers prepared wholly by solid phase peptide synthesis. The amino acids glycine, arginine and lysine formed the dendrimer with ketoprofen tethered either to the lysine side-arm (N) or periphery of dendrimeric branches. Passive diffusion, sonophoresis- and iontophoresis-assisted permeation of each peptide dendrimer-drug conjugate (D1–D4) was studied across mouse skin, both in vitro and in vivo. In addition, skin toxicity of dendrimeric conjugates when trialed with iontophoresis or sonophoresis was also evaluated. All dendrimeric conjugates improved aqueous solubility at least 5-fold, compared to ketoprofen alone, while also exhibiting appreciable lipophilicity. In vitro passive diffusion studies revealed that ketoprofen in its native form was delivered to a greater extent, compared with a dendrimer-conjugated form at the end of 24\ua0h (Q(μg/cm): ketoprofen (68.06\ua0±\ua03.62)\ua0>\ua0D2 (49.62\ua0±\ua02.92)\ua0>\ua0D4 (19.20\ua0±\ua00.89)\ua0>\ua0D1 (6.45\ua0±\ua00.40)\ua0>\ua0D3 (2.21\ua0±\ua00.19). However, sonophoresis substantially increased the skin permeation of ketoprofen-dendrimer conjugates in 30\ua0min (Q(μg/cm): D4 (122.19\ua0±\ua07.14)\ua0>\ua0D2 (66.74\ua0±\ua03.86)\ua0>\ua0D1 (52.10\ua0±\ua03.22)\ua0>\ua0D3 (41.66\ua0±\ua03.22)) although ketoprofen alone again proved superior (Q: 167.99\ua0±\ua09.11\ua0μg/cm). Next, application of iontophoresis was trialed and shown to considerably increase permeation of dendrimeric ketoprofen in 6\ua0h (Q(μg/cm): D2 (711.49\ua0±\ua039.14)\ua0>\ua0D4 (341.23\ua0±\ua016.43)\ua0>\ua0D3 (89.50\ua0±\ua04.99)\ua0>\ua0D1 (50.91\ua0±\ua02.98), with a Qvalue of 96.60\ua0±\ua05.12\ua0μg/cmfor ketoprofen alone). In vivo studies indicated that therapeutically relevant concentrations of ketoprofen could be delivered transdermally when iontophoresis was paired with D2 (985.49\ua0±\ua043.25\ua0ng/mL). Further, histopathological analysis showed that the dendrimeric approach was a safe mode as ketoprofen alone. The present study successfully demonstrates that peptide dendrimer conjugates of ketoprofen, when combined with non-invasive modalities, such as iontophoresis can enhance skin permeation with clinically relevant concentrations achieved transdermally

Benchmarking natural-language parsers for biological applications using dependency graphs

BACKGROUND: Interest is growing in the application of syntactic parsers to natural language processing problems in biology, but assessing their performance is difficult because differences in linguistic convention can falsely appear to be errors. We present a method for evaluating their accuracy using an intermediate representation based on dependency graphs, in which the semantic relationships important in most information extraction tasks are closer to the surface. We also demonstrate how this method can be easily tailored to various application-driven criteria. RESULTS: Using the GENIA corpus as a gold standard, we tested four open-source parsers which have been used in bioinformatics projects. We first present overall performance measures, and test the two leading tools, the Charniak-Lease and Bikel parsers, on subtasks tailored to reflect the requirements of a system for extracting gene expression relationships. These two tools clearly outperform the other parsers in the evaluation, and achieve accuracy levels comparable to or exceeding native dependency parsers on similar tasks in previous biological evaluations. CONCLUSION: Evaluating using dependency graphs allows parsers to be tested easily on criteria chosen according to the semantics of particular biological applications, drawing attention to important mistakes and soaking up many insignificant differences that would otherwise be reported as errors. Generating high-accuracy dependency graphs from the output of phrase-structure parsers also provides access to the more detailed syntax trees that are used in several natural-language processing techniques

Nanocrystal-Based Topical Gels for Improving Wound Healing Efficacy of Curcumin

Topical curcumin shows poor local availability because of its low aqueous solubility and inadequate tissue absorption. Curcumin nanocrystals were prepared by sonoprecipitation followed by lyophilization to improve surface area and solubility. The formulation was optimized by the Design of Experiment (DoE) approach. The nanocrystals were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), powder x-ray diffraction (PXRD), practical yield and in vitro drug release studies. The nanocrystal-incorporated gel was evaluated for drug content, ex vivo permeation, in vivo skin irritation, and in vivo wound healing activity. Time of sonication and amplitude influenced the optimization of curcumin nanocrystals, but the effect of stabilizer concentrations was not significant beyond 0.5% w/w. SEM images of curcumin nanocrystals revealed irregular and plate-shaped particles with rough surfaces. PXRD patterns of curcumin nanocrystals showed low crystallinity compared to unprocessed curcumin powder. An in vitro drug release study demonstrated significant improvement in the percentage cumulative drug release in the form of nanocrystals compared to the unprocessed curcumin, and the release profile exhibited first-order kinetics. Curcumin nanocrystal gel showed 93.86% drug content and was free of skin irritation potential. Excision wound healing activity in albino rats showed that the curcumin nanocrystal gel exhibited significantly faster wound contraction than curcumin powder-incorporated gel

Nanocrystal-Based Topical Gels for Improving Wound Healing Efficacy of Curcumin

Topical curcumin shows poor local availability because of its low aqueous solubility and inadequate tissue absorption. Curcumin nanocrystals were prepared by sonoprecipitation followed by lyophilization to improve surface area and solubility. The formulation was optimized by the Design of Experiment (DoE) approach. The nanocrystals were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), powder x-ray diffraction (PXRD), practical yield and in vitro drug release studies. The nanocrystal-incorporated gel was evaluated for drug content, ex vivo permeation, in vivo skin irritation, and in vivo wound healing activity. Time of sonication and amplitude influenced the optimization of curcumin nanocrystals, but the effect of stabilizer concentrations was not significant beyond 0.5% w/w. SEM images of curcumin nanocrystals revealed irregular and plate-shaped particles with rough surfaces. PXRD patterns of curcumin nanocrystals showed low crystallinity compared to unprocessed curcumin powder. An in vitro drug release study demonstrated significant improvement in the percentage cumulative drug release in the form of nanocrystals compared to the unprocessed curcumin, and the release profile exhibited first-order kinetics. Curcumin nanocrystal gel showed 93.86% drug content and was free of skin irritation potential. Excision wound healing activity in albino rats showed that the curcumin nanocrystal gel exhibited significantly faster wound contraction than curcumin powder-incorporated gel