Molecular dynamics and physical stability of amorphous nimesulide drug and its binary drug-polymer systems

yesIn this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The re-crystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer. This polymer proved to be the best NMS’s stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS’s re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.The authors J.K., Z.W., K.G. and M.P., are grateful for the financial support received within the Project No. 2015/16/W/NZ7/00404 (SYMFONIA 3) from the National Science Centre, Poland. H.M. and L.T. are supported by Science Foundation Ireland under grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre)

Kinetics of Intrahepatic Hepatitis C Virus (HCV)-Specific CD4+ T Cell Responses in HCV and Schistosoma mansoni Coinfection: Relation to Progression of Liver Fibrosis

The kinetics of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses and their role in progression of fibrosis have not previously been characterized. Subjects with HCV/Schistosoma mansoni coinfection have a more rapid progression of HCV liver fibrosis than do those with HCV infection alone. The present prospective longitudinal study compared the liver histology, HCV-specific intrahepatic and peripheral CD4+ T cell proliferative responses, and cytokines (enzyme-linked immunospot) in 48 subjects with unresolved acute HCV infection with or without S. mansoni coinfection, at 6-10 months after acute infection and at the end of follow-up ( months), and the findings were correlated 96±8.7 to the rate of progression of fibrosis per year. Coinfected subjects had significant worsening of fibrosis, compared with subjects with HCV infection alone. At baseline, subjects with HCV infection alone had stronger multispecific intrahepatic HCV-specific CD4+ T helper 1 responses than did coinfected subjects, who had either no responses or weak, narrowly focused responses, and, over time, these T cell responses were maintained only in the liver. The rate of progression of fibrosis and virus load inversely correlated with intrahepatic HCV-specific CD4+ T cell response. The present prospective analysis indicates that enhancement of progression of liver fibrosis is associated with failure to develop early, multispecific, HCV-specific CD4+ Th1 responses, suggesting that novel therapeutic approaches inducing strong cellular immune responses might limit subsequent liver damage in individuals with chronic hepatitis

Evidence for the existence of powder sub-populations in micronized materials : Aerodynamic size-fractions of aerosolized powders possess distinct physicochemical properties

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: To investigate the agglomeration behaviour of the fine ( 12.8 µm) particle fractions of salmeterol xinafoate (SX) and fluticasone propionate (FP) by isolating aerodynamic size fractions and characterising their physicochemical and re-dispersal properties. Methods: Aerodynamic fractionation was conducted using the Next Generation Impactor (NGI). Re-crystallized control particles, unfractionated and fractionated materials were characterized for particle size, morphology, crystallinity and surface energy. Re-dispersal of the particles was assessed using dry dispersion laser diffraction and NGI analysis. Results: Aerosolized SX and FP particles deposited in the NGI as agglomerates of consistent particle/agglomerate morphology. SX particles depositing on Stages 3 and 5 had higher total surface energy than unfractionated SX, with Stage 5 particles showing the greatest surface energy heterogeneity. FP fractions had comparable surface energy distributions and bulk crystallinity but differences in surface chemistry. SX fractions demonstrated higher bulk disorder than unfractionated and re-crystallized particles. Upon aerosolization, the fractions differed in their intrinsic emission and dispersion into a fine particle fraction (< 5.0 µm). Conclusions: Micronized powders consisted of sub-populations of particles displaying distinct physicochemical and powder dispersal properties compared to the unfractionated bulk material. This may have implications for the efficiency of inhaled drug deliveryPeer reviewe

Changes in Mood States and Biomarkers During Peginterferon and Ribavirin Treatment of Chronic Hepatitis C

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74953/1/j.1572-0241.2008.02106.x.pd

Sferična kristalizacija zdravilnih učinkovin

Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.Sferična kristalizacija je postopek izdelave večjih delcev z aglomeracijo manjših med samo kristalizacijo. Najpogosteje uporabljeni tehniki za izdelavo takšnih delcev sta sferična aglomeracija in kvaziemulzija z difuzijo topila. Sistem z difuzijo amoniaka in kristalo-ko-aglomeracija sta razširitvi teh dveh metod. Z nadzorovanjem procesnih parametrov med kristalizacijo, kot sta temperatura in hitrost mešanja, z izbiro lastnosti in množine topil ter z izbiro pomožnih snovi, lahko vplivamo na nastanek aglomeratov in izdelamo sferične delce želenih velikosti, primerne poroznosti ali trdote. Raziskovalci poročajo, da imajo izdelani delci izboljšane pretočne lastnosti, izboljšane druge fizikalne in mehanske lastnosti zaradi česar so primerni za direktno tabletiranje. V nekaterih primerih lahko ob vgradnji ustreznih pomožnih snovi, ki jih dodamo med procesom sferične kristalizacije, izboljšamo tudi biofarmacevtske lastnosti zdravilnih učinkovin vključno s povečanjem biološke uporabnosti