On the factors influencing the extrusion strain, particle size and dissolution behavior of multiparticulate systems obtained by extrusion/spheronization

International audienceThe increased need for predicting the properties of granular systems has become a growing challenge for the pharmaceutical industry. Experimental design has hastened developments in the field of pharmaceuticals and helped scientists to better understand the behavior of particles in the wet granulation process. In this research, the production of pellets containing binary mixtures of high-dose paracetamol (40, 60 and 80%) and microcrystalline cellulose (Microcel® MC 101) was evaluated. Three commercial grades of the drug at three concentrations each were used. Pellets were prepared by axial and radial extrusion systems and then spheronized. The formulation and process, as input variables, were analyzed using a response surface methodology (RSM). The responses considered as output variables were energy spent on the extrusion, particle size distribution of the granules and the parameters of the Weibull function, time (τd) and shape (β), in terms of dissolution behavior. The results indicated that less energy is spent during the radial extrusion process for commercial-grade paracetamol with 80% of drug and fine particle size. Also, these conditions resulted in a higher percentage of the pellet being in the main size fraction (0.800-1.250 mm) and a larger time required to dissolve 63.2% of the drug (τd). It was observed that the τd value decreased with increasing particle size of the powder formulation. The β parameter was strongly influenced by the drug load and paracetamol grade for both extrusion procedures. The higher the content (percentage) and the smaller the particle size of the drug the higher the β parameter, indicating a parabolic shape changing to sigmoidal shape for the behavior of this parameter. These findings concerning formulations containing paracetamol can be extended to other drugs of equivalent particle size and water-solubility. The RSM tool was able to identify the manner and amplitude of the effects of the input variables on the output variables studied

Dinâmica do setor turístico em Ponta Porã – MS, Brasil

O turismo é um importante setor econômico para a geração de renda e emprego. Apesar do potencial turístico existente no município de Ponta Porã, MS, Brasil, fronteira com Pedro Juan Caballero-Paraguai, a região não é reconhecida no setor. Esse trabalho analisa a dinâmica do mercado de turismo na cidade e busca identificar a existência de aglomeração produtiva, a fim de evidenciar a importância da atividade turística para o município, usando o modelo estrutural diferencial ampliado. Os resultados mostram que o emprego no setor turístico de Ponta Porã cresceu acima da média do estado e que a cidade possui vantagem locacional e especialização no setor. Em relação à existência de aglomeração produtiva de bens e serviços turísticos, os resultados reforçam a existência destas no município e que o mesmo possui condições favoráveis ao desenvolvimento de APL’s de turismo

Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia

IGHV mutational status and ZAP-70 or CD38 expression correlate with clinical course in B-cell chronic lymphocytic leukaemia (CLL). The three markers may be discordant in the single case and there is no consensus on their combined use in clinical practise. This multicenter study investigated this issue. Two-hundred and sixty-two Binet stage A patients were studied for the three markers. Sixty patients were profiled with HG-U133A gene expression chips. Disease progression was determined by time from diagnosis to treatment (TTT). The probability of being treatment-free at 3 years was significantly shorter in patients with unmutated IGHV genes (IGHVunmut 66% vs. 93%, chi square of log-rank = 30, P < 0.0001), ZAP-70 positive (ZAP-70pos 73% vs. 96%, chi square of log-rank = 8.2, P = 0.004) or CD38-positive cells (CD38pos 68% vs. 91%, chi square of log-rank = 21, P < 0.0001). Cox multivariate regression analysis showed that the three markers had an independent predictive value for TTT of similar power. A prognostic system based on presence of none (low-risk), one (intermediate-risk) or two or three (high-risk) markers was generated. Based on such criteria, 56%, 23% and 21% of cases were clustered in low (HR = 1), intermediate [HR = 2.8, 95% confidence interval (CI) 2.4-5.8] and high-risk group (HR = 8.0, 95% CI 3.9-16.2). Specific transcriptional patterns were significantly associated with risk groups

Effects of the Ottonia martiana Miq. (Piperaceae) extract on dog's ocular surface

The anesthetics effects of aqueous extract of Ottonia martiana leaves were studied on the ocular surface of healthy beagle dogs. The dogs were divided in three groups (n=15): control group (CG), proxymetacaine group (PG) and Ottonia group (OG), which were treated with 0.9% saline, 0.5% proxymetacaine hydrochloride ophthalmic solution and O. martiana extract respectively. An oftalmic evaluation was performed before the treatments. Eye drops were instilled at time 0 (T0) and 3 minutes later (T3). Axial corneal sensitivity was evaluated by esthesiometry 5 and 10 minutes after T0. Tear production and intraocular pressure were evaluated 10 minutes after T0. Slit lamp biomicroscopy was performed 10 and 20 minutes after T0 and the eyes were stained with fluorescein 20 minutes after T0. The STT was reduced in PG. Conjunctival hyperemia was observed in 13 animals from PG and constituted the only ocular alteration observed during the study. Esthesiometry revealed a decreased corneal sensitivity for PG and OG. Those results show that the O. martiana extract acts reducing corneal sensitivity in dogs. Moreover, its use does not decrease the tear production and does not cause any clinical ophthalmic alteration