Preparation of Porous Anhydrous MgCl2 Particles by Spray Drying Process

Polyethylene (PE) is indispensable materials in daily lives. The catalyst is necessary to produce PE. Ziegler-Natta catalysts were mostly used to produce PE which consisted of MgCl2/TiCl4 system. Polyethylene particle was reported to replicate the shape of the catalyst particles or catalyst support particles. Therefore, the MgCl2 supports need to satisfy various requirements regarding particle morphology such as shape, particle size with uniform size distribution as well as the porosity. In this research, the preparation of MgCl2 particles from irregular shape of anhydrous MgCl2 by spray drying method was studied. However, because of the hygroscopic properties of anhydrous MgCl2, all steps of experiment in this work were operated under dry N2 atmosphere. The effect of type of alcohol, ethanol, n-propanol and n-butanol as solvent which was used to dissolve MgCl2 before feeding through the spray drying on the particle properties were investigated. The amount of residual alcohol (alcoholic hydroxyl group content), morphology, specific surface area, porosity and crystallinity were determined by GC method, scanning electron microscope (SEM), N2 sorption analyzer and X-ray diffraction (XRD), respectively. The results revealed that spray drying process can produce the porous anhydrous MgCl2 particles which have rough surface, higher porosity and lower crystallinity than original anhydrous MgCl2

In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide

Background: Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy. Methods and Findings: Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohisto-chemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures. Conclusions: These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective against HIV-1 infection in our algorithm. These data support the use of tenofovir for pre-exposure prophylaxis. © 2010 Rohan et al

vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide

Abstract Background: Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)—if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18–64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP

A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

Objective: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration: ClinicalTrials.gov NCT01232803

Impact of Educational Intervention on Anticoagulation Control Using SAMe-TT22R2 Score-Guided Strategy in Atrial Fibrillation

Background: An educational-behavioral intervention has been shown to improve anticoagulation control with warfarin in atrial fibrillation (AF) patients, but widespread application may not be practical. The SAMe-TT2R2 score was formulated to identify the likelihood of achieving optimal time in therapeutic range (TTR). Objectives: The authors conducted a randomized controlled trial to evaluate the impact of a SAMe-TT2R2 score-guided strategy for an educational-behavioral intervention, compared with usual care on patient's anticoagulation control. Methods: Anticoagulant-naive adult AF patients were randomized to a SAMe-TT2R2 score-guided strategy or usual care. In the SAMe-TT2R2 score-guided strategy group, scores 0 to 2 received usual care, >2 received educational-behavioral intervention plus usual care. All received warfarin targeting international normalized ratio 2.0 to 3.0. Primary outcome was TTR at 12 months. Secondary outcomes included TTR at 6 months, thromboembolic and bleeding events, major adverse cardiovascular events at 12 months, and change in AF knowledge at 6 and 12 months. Results: A total of 320 patients (mean age 69.5 years; 48.8% female) were randomized to a SAMe-TT2R2 score-guided strategy plus usual care (n = 156) or usual care alone (n = 164). Mean CHA2DS2-VASc score and SAMe-TT2R2 score were 3.1 ± 1.4 and 3.3 ± 0.9, respectively. At 12 months, mean TTR was not significantly different between groups (41.0 [95% CI: 36.7-45.2] in the SAMe-TT2R2 score-guided strategy vs 40.2 [95% CI: 35.9-44.4] with usual care, and the difference between the 2 groups was 0.7 [95% CI: −5.2 to 6.6]). There were no significant differences in secondary outcomes. Conclusions: SAMe-TT2R2 score-guided strategy for an educational-behavioral intervention, compared with usual care did not significantly improve outcomes over 12 months. (Thai Clinical Trials Registry identification number TCTR20180711003

NaOH modified WO3/SiO2 catalysts for propylene production from 2-butene and ethylene metathesis

A WO3/SiO2 catalyst is used in industry to produce propylene from 2-butene and ethylene metathesis. Catalysts with various WO3 loading (4% to 10%) were prepared by impregnation and tested for the metathesis of ethene and trans-2-butene. Ion exchange of NaOH onto the WO3/SiO2 catalyst was used to mitigate the acidity of the catalysts in a controlled way. At low WO3 loading, the treatment with large amounts of NaOH resulted in a significant decrease in metathesis activity concomitant with significant W leaching and marked structural changes (XRD, Raman). At higher WO3 loading (6% to 10%), the treatment with NaOH mainly resulted in a decrease in acidity. FT-IR experiments after adsorption of pyridine showed that the Lewis acidic sites were poisoned by sodium. Nevertheless, the metathesis activity remained constant after the NaOH treatment. This suggested that the remaining acidity on the catalyst was enough to ensure the efficient formation of the carbene active sites. Interestingly, Na poisoning resulted in some modification of the selectivity. The mitigation of acidity was shown to favor propene selectivity over the formation of isomerization products (cis-2-butene, 1-butene, etc.). Moreover, treatment with NaOH led to a shorter induction period and reduced coke formation on the WO3/SiO2 catalyst