Formulation of sublingual promethazine hydrochloride tablets for rapid relief of motion sickness

The delivery of antihistaminic agents via the oral route is problematic, especially for elderly patients. This study aimed to develop a sublingual formulation of promethazine hydrochloride by direct compression, and to mask its intensely bitter taste. Promethazine hydrochloride (PMZ) sublingual tablets prepared by direct compression were optimized using Box-Behnken full factorial design. The effect of a taste-masking agent (Eudragit E 100, X1), superdisintegrant (crospovidone; CPV, X2) and lubricant (sodium stearyl fumarate; SSF, X3) on sublingual tablets’ attributes (responses, Y) was optimized. The prepared sublingual tablets were characterized for hardness (Y1), disintegration time (Y2), initial dissolution rate (IDR; Y3) and dissolution efficiency after 30 min (Dissolution Efficiency (DE); Y4). The obtained results showed a significant positive effect of the three independent factors on tablet hardness (P < 0.05), and the interactive effect of Eudragit E 100 and CPV on tablet hardness was significant. Disintegration time was mainly affected by Eudragit E 100 and CPV concentrations. Moreover, IDR was employed to assess the taste masking effect, lower values were obtained at higher Eudragit E 100 concentration despite it was statistically insignificant (p > 0.05). Optimized formulation that was suggested by the software was composed of: Eudragit E 100 (X1) = 2.5% w/w, CPV (X2) = 4.13% w/w, and SSF (X3) = 1.0% w/w. The observed values of the optimized formula were found to be close to the predicted optimized values. The Differential Scanning Calorimetric (DSC) studies indicated no interaction between PMZ and tablet excipients.     

Surgical site infections following gastrointestinal surgery in Palestine: a multicentre,prospective cohort study

Background

Surgical site infection (SSI) is defined as operation-related infections that occur at or near surgical incisions within 30 days after surgery. SSI is the most common postoperative complication and leads to increased morbidity and mortality among surgical patients. In Palestine, prospective multicentre studies on the epidemiology of SSI are lacking. We aimed to describe SSI epidemiology following gastrointestinal surgery in Palestine.

TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing

TRIM7 catalyzes the ubiquitination of multiple substrates with unrelated biological functions. This cross-reactivity is at odds with the specificity usually displayed by enzymes, including ubiquitin ligases. Here we show that TRIM7′s extreme substrate promiscuity is due to a highly unusual binding mechanism, in which the PRYSPRY domain captures any ligand with a C-terminal helix that terminates in a hydrophobic residue followed by a glutamine. Many of the non-structural proteins found in RNA viruses contain C-terminal glutamines as a result of polyprotein cleavage by 3C protease. This viral processing strategy generates novel substrates for TRIM7 and explains its ability to inhibit Coxsackie virus and norovirus replication. In addition to viral proteins, cellular proteins such as glycogenin have evolved C-termini that make them a TRIM7 substrate. The ‘helix-ΦQ’ degron motif recognized by TRIM7 is reminiscent of the N-end degron system and is found in ~1% of cellular proteins. These features, together with TRIM7′s restricted tissue expression and lack of immune regulation, suggest that viral restriction may not be its physiological function.     

Dissolution and bioavailability improvement of bioactive apigenin using solid dispersions prepared by different techniques

Apigenin (APG) is a poorly soluble bioactive compound/nutraceutical which shows poor bioavailability upon oral administration. Hence, the objective of this research work was to develop APG solid dispersions (SDs) using different techniques with the expectation to obtain improvement in its in vitro dissolution rate and in vivo bioavailability upon oral administration. Different SDs of APG were prepared by microwave, melted and kneaded technology using pluronic-F127 (PL) as a carrier. Prepared SDs were characterized using “thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) spectrometer, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM)”. After characterization, prepared SDs of APG were studied for in vitro drug release/dissolution profile and in vivo pharmacokinetic studies. The results of TGA, DSC, FTIR, PXRD and SEM indicated successful formation of APG SDs. In vitro dissolution experiments suggested significant release of APG from all SDs (67.39–84.13%) in comparison with control (32.74%). Optimized SD of APG from each technology was subjected to in vivo pharmacokinetic study in rats. The results indicated significant improvement in oral absorption of APG from SD prepared using microwave and melted technology in comparison with pure drug and commercial capsule. The enhancement in oral bioavailability of APG from microwave SD (319.19%) was 3.19 fold as compared with marketed capsule (100.00%). Significant enhancement in the dissolution rate and oral absorption of APG from SD suggested that developed SD systems can be successfully used for oral drug delivery system of APG.     

Preoperative frailty predicts postoperative outcomes in intestinal-cutaneous fistula repair

BackgroundThe outcomes of operative repair of intestinal-cutaneous fistulas vary widely throughout the literature. We aimed to investigate whether the modified frailty index-5 is a reliable tool to account for physiologic reserve and whether it serves as a predictor of Clavien-Dindo grade IV complications in those with intestinal-cutaneous fistulas undergoing operative repair.MethodsWe queried the American College of Surgeons National Surgical Quality Improvement Program 2006 to 2017 database to include patients who underwent intestinal-cutaneous fistulas repair. The outcome of interest was 30-day Clavien-Dindo grade IV complications. The incidence of 30-day post-operative Clavien-Dindo grade IV complications were evaluated based on calculated modified frailty index-5 score. Multivariable logistic regression analyses were performed to assess the association of Clavien-Dindo grade IV complications and modified frailty index-5.ResultsA total of 3,995 patients were identified who underwent an intestinal-cutaneous fistulas repair. The median age (interquartile range) was 57 years (46, 67), and most patients were female (2,143 [53.7%]), White (3,206 [80.3%]), and 1,512 (38.2%) were obese. After adjusting for relevant covariates such as demographics, comorbidities, and operative details, modified frailty index-5 was independently associated with Clavien-Dindo grade IV complications (odds ratio = 2.81, 95% confidence interval 1.64–4.82; P < .001).ConclusionModified frailty index-5 is an independent predictor of Clavien-Dindo grade IV complications following intestinal-cutaneous fistulas repair. It can be used to account for physiologic reserve, thus reducing the variability of outcomes reported for intestinal-cutaneous fistulas repair.