This study was aimed to boost up the dissolution rate of a sparingly aqueous soluble BCS Class II drug pitavastatin (PTV) by solid dispersion (SD) techniques using two hydrophilic polymers poloxamer 407 and hydroxypropylmethylcellulose (HPMC). Low aqueous solubility of PTV is associated with less oral bioavailability, and a real challenge in preparing appropriate dosage form. To enhance the aqueous solubility, physical mixing and SD formulations of PTV were developed by fusion and solvent evaporation methods using two hydrophilic polymers, poloxamer 407 and HPMC. Scanning electron microscopy (SEM) investigation indicated that PTV molecules were homogeneously dispersed in carrier prepared by different formulation methods at 1:2 and 1:3 ratios of PTV: polymer assuming amorphous SD state. The thermogravimetric profiles demonstrated that PTV was stable up to 198°C and began to decompose rapidly with significant weight loss as the temperature was raised over 190°C. Formulations prepared by SD techniques were stable at high temperature. In vitro studies illustrated that cumulative drug release of PTV: HPMC/poloxamer 407 formulations prepared by physical mixing, fusion and solvent evaporation techniques were better compared to pure PTV powder (61.42±0.91%). Among all the approaches, formulations prepared by solvent evaporation and fusion methods displayed higher cumulative releases of PTV than physical mixing formulations. The results of current study clearly indicated that PTV: HPMC/poloxamer 407 (1:2) formulations (S3, S1) developed by solvent evaporation method possess enhanced dissolution profile (96.06%; 95.62%) than the fusion SD formulations (F3; 94.62%, F1; 87.05%). Whereas PTV physical mixing formulations (P2; 82.32%, P4; 80.28%) containing high amount of carrier polymers (ratio 1:3) exhibited superior in vitro dissolution rates than formulations (P3; 68.70%, P1; 71.52%) having less quantity (ratio 1:2) of HPMC/poloxamer 407. It is apparent from the findings of this study that SD formulations (S3, S1, F3, F1) of PTV with HPMC/poloxamer 407 is a very promising approach for improving the in vitro dissolution profile of the sparingly aqueous soluble PTV. Moreover, 1:2 ratio formulations prepared by fusion and solvent evaporation SD approaches were found more effective to upgrade the release rate of PTV than the 1:3 formulations. Dhaka Univ. J. Pharm. Sci. 20(3): 325-336, 2022 (June) Centennial Special Issue
Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations. Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, NCT02477046.
Escherichia coli (E. coli) pathotypes are the most common cause of diarrhea, especially in developing countries. Environmental Enteric Dysfunction (EED) is presumed to be the result of infection with one or more pathotypes and can affect intestinal health and childhood growth. We sought to investigate the association of E. coli pathotypes infection with biomarkers of EED and nutritional status among slum-dwelling malnourished children in Bangladesh. This study comprised a total of 1050 stunted and at risk of stunting children. TaqMan Array Card assays were used to determine the presence of E. coli pathotypes in feces. Prevalence of infection with EAEC was highest (68.8%) in this cohort of children, followed by EPEC (55.9%), ETEC (44%), Shigella/EIEC (19.4%) and STEC (3.2%). The levels of myeloperoxidase and calprotectin were significantly higher in EAEC (P=0.02 and P=0.04), EPEC (P=0.02 and P=0.03) and Shigella/EIEC (P=0.05 and P=0.02) positive participants while, only calprotectin was significantly higher in ETEC (P=0.01) positive participants. Reg1B was significantly higher in participants with EAEC (P=0.004) while, neopterin levels were significantly lower in ETEC (P=0.003) and Shigella/EIEC (P=0.003) positive cases. A significant positive relationship was observed between EAEC and fecal levels of Reg1B (β = 0.28; 95% CI = 0.12, 0.43; p-value<0.001). Besides, ETEC was found to be positively and significantly associated with the levels of calprotectin (β = 0.14; 95 percent CI = 0.01, 0.26; p-value=0.037) and negatively with neopterin (β = -0.16; 95% CI = -0.30, -0.02; p-value=0.021). On the other hand, infection with EPEC was found to be negatively associated with length-for-age (β = -0.12; 95% CI = -0.22, -0.03; p-value=0.011) and weight-for-age (β = -0.11; 95% CI = -0.22, -0.01; p-value=0.037). The study findings suggest that infection with certain E. coli pathotypes (EAEC and ETEC) influences gut health and EPEC is associated with linear growth and underweight in Bangladeshi children.
Background Understanding pathogen-specific relationships with climate is crucial to informing interventions under climate change. Methods We matched spatiotemporal temperature, precipitation, surface water, and humidity data to data from a trial in rural Bangladesh that measured diarrhea and enteropathogen prevalence in children 0-2 years from 2012-2016. We fit generalized additive models and estimated percent changes in prevalence using projected precipitation under Shared Socio-Economic pathways describing sustainable development (SSP1), middle of the road (SSP2), and fossil fuel development (SSP5) scenarios. Findings An increase from 15 degrees C to 30 degrees C in weekly average temperature was associated with 5.0% higher diarrhea, 6.4% higher Norovirus, and 13.0% higher STEC prevalence. Above-median precipitation was associated with 1.27-fold (95% CI 0.99, 1.61) higher diarrhea; higher Cryptosporidium, tEPEC, ST-ETEC, STEC, Shigella, EAEC, Campylobacter, Aeromonas, and Adenovirus 40/41; and lower aEPEC, Giardia, Sapovirus, and Norovirus prevalence. Other associations were weak or null. Compared to the study period, diarrhea prevalence was similar under SSP1 (7%), 3.4% (2.7%, 4.3%) higher under SSP2, and 5.7% (4.4%, 7.0%) higher under SSP5. Prevalence of pathogens responsible for a large share of moderate-to-severe diarrhea in this setting (Shigella, Aeromonas) were 13-20% higher under SSP2 and SSP5. Interpretation Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Under likely climate change scenarios, we projected increased prevalence of diarrhea and enteropathogens responsible for clinical illness. Our findings inform pathogen-specific adaptation and mitigation strategies and priorities for vaccine development.
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