Background Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children. Methods We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old. Results We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months ( P < .001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid. Conclusions Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden.
The present study deals with the formulation and evaluation of Fexofenadine hydrochloride (HCl) loaded sustained release microspheres by emulsion solvent evaporation method with Eudragit RL 100. The effects of percent drug loading on drug encapsulation efficiency, drug content and drug release rate were assessed. In vitro dissolution study was performed spectrophotometrically according to USP paddle method using phosphate buffer (pH 6.8) for 10 hours. The release rate of Fexofenadine HCl from the microspheres was significantly increased with the increase of drug loading. The drug release patterns were simulated in different kinetic orders such as zero order release kinetics, first order release kinetics, Higuchi release kinetics, Korsmeyer-Peppas release kinetics and Hixson-Crowell release kinetics to assess the release mechanism and Higuchi release kinetics was found to be the predominant release mechanism. Morphological changes due to different drug loading were assessed by scanning electron microscopic (SEM) technique. Differential scanning calorimetry and fourier transform infra-red (FT-IR) spectroscopy was performed to evaluate compatibility of drug with the polymer. A statistically significant variation indrug encapsulation efficiency and release rate was observed for variation in drug loading.
Polymeric microspheres of gliclazide were prepared to provide sustained release delivery of gliclazide to aid in continuous therapy with high margin of safety. Gliclazide was microencapsulated with different polymers namely HPMC K100LV, Ethocel (20 cps) and HPMC K100M by emulsion solvent evaporation technique using acetone as internal phase and liquid paraffin as external phase. Seventeen formulations were prepared using different drug loading and polymeric ratio of which nine formulations were prepared by a 3 2 full factorial design. Each formulation was evaluated for flow properties, particle size, surface morphology, drug entrapment efficiency, drug release and compatibility. Yield (%) for every batch of microspheres was measured. Flow properties of the microspheres were examined by determining bulk density, tapped density, Carr's compressibility index, Hausner ratio and angle of repose. Particle size distribution was examined by sieving and particle size analyzer. Surface morphology was determined by scanning electron microscopy (SEM). In-vitro drug release was studied in a paddle type dissolution apparatus (USP Type II Dissolution Apparatus) for a period of 8 hours at 37°C using phosphate buffer ( pH 7.4). FTIR and DSC studies established compatibility of the drug with the polymers. Microspheres prepared with Ethocel (20 cps) and HPMC K100M were free flowing than those prepared only with HPMC K100LV. Entrapment efficiencies were within 75.88-99.69%. Microspheres prepared with Ethocel (20 cps) and HPMC K100M showed more sustained release when compared to microspheres prepared with HPMC K100LV only. Increase in drug loading resulted in increased drug release for the microspheres. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranging from diffusion controlled to anomalous type. Ethocel and HPMC K100M in a ratio of 1:3 exhibited better sustained release properties than 1:1 and 3:1 ratios. The release rate of gliclazide from microspheres prepared with Ethocel (20 cps) and HPMC K100M was less than the release rate of gliclazide from microspheres prepared with HPMC K100LV, demonstrating Ethocel and HPMC K100M as suitable polymeric blend for preparing the controlled release formulation for gliclazide whereas, HPMC K100LV was found not suitable candidate when used alone as a polymer.
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