Stability of Enveloped and Nonenveloped Viruses in a Stable Gelatin Liquid Formulation

The thermal stability of relevant viruses in gelatin liquid formulations for medical research and application is poorly understood. Bovine herpesvirus (BHV) was used as a model virus to examine the molecular weight (MW), concentration and gelatin type and to optimize virus stability in liquid formulations at 25 °C and 4 °C. Using the model virus stable liquid formulation, the stability of multiple enveloped and nonenveloped RNA and DNA viruses, including parainfluenza virus (PIV), reovirus (RV), BHV, and adenovirus (AdV), was monitored over up to a 30-week storage period. The BHV model virus was considered stable after 3 weeks in hydrolyzed gelatin (MW: 4000) with a 0.8 LRV (log10 reduction value) at 25 °C or a 0.2 LRV at 4 °C, compared to the stabilities observed in higher MW gelatin (60000 and 160000) with an LRV above 1. Based on the gelatin type, BHV in B-type gelatin samples were unexpectantly more stable than in A-type gelatin sample. All four viruses exhibited stability at 4 °C for at least 8 weeks, BHV or AdV remained stable for over 30 weeks of storage, and at 25 °C, AdV and RV remained stable for 8 weeks. The results demonstrated that 5% hydrolyzed gelatin can act as a relevant stabilizer for the thermal stability of viruses in medical research and application.

Comparison of three galenic forms of lamivudine in young West African children living with Human Immunodeficiency Virus

Background Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet. Method HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach. Results One hundred and fifty children (age: 2.5 years (1.9–3.2), weight 11.1 (9.5–12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic. Conclusion This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV–1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.

Efficacy Bacillus thuringiensis var. israelensis serotype H-14 (Bti H-14) for control Aedes spp. density in Denpasar, Bali

Background: A liquid bioinsecticide formulation containing Bacillus thuringiensis var. israelensis Serotype H-14 (Bti H-14) was tested in the field in household containers. The aim was to determine the effectiveness of Bti H-14 biolarvicide in controlling the density of Aedes spp. Larvae.Methods: This study was conducted in two phases of testing. First, to test the effective dose with 5 doses, namely (50 ul, 40 ul, 30 ul, 20 ul, and 10 ul) in 2.5 liters of water. Furthermore, the number of deaths was calculated after 24 hours of treatment and control by doing four repetitions. In the second phase, by conducting tests on containers in the household as many as 3171 containers were continuously observed every month, given Bti H-14 for 6 months. Observations were made before and after the application of Bti H-14 on larva density, mosquito density, and dengue cases. Data analysis was performed using paired t-test. Bti H-14 formulation to kill 50% of mosquito larvae (LC50) within 6 hours requires a concentration of 4 µl per liter.Results: Bti H-14 liquid formulation with delta-endotoxin and spores content of 600 ITU per ml or 1.2x109 CFU is effective in reducing larva density in household containers if done regularly.Conclusions: Bti H-14 liquid formulation is proven to be effective and easy to use for the control of Aedes larvae.

Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13–113.6), 98.08% (88.04–109.2), and 97.52% (84.9–112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

Silicon reduces Fusarium Head Blight Development in Barley

Background: Silicon (Si) can directly or indirectly enhance plant resistance to fungal pathogens, but no report is available concerning the effectiveness of Si in decreasing Fusarium Head Blight (FHB) disease on barley (Hordeum vulgare L.). Objective and Methods: The evaluation of Si supplied to barley incorporated into the soil and as a foliar spray against four FHB species under controlled conditions was investigated. In addition, the potential resistance mechanisms related to the reduction of Disease Incidence (DI) and Disease Severity (DS) measured at 7, 14, 21, and 28 days post-inoculation (dpi) were proposed. Four Si concentrations of both a SiO2 powder incorporated into the soil as a solid source, i.e., of 0.00, 0.50, 1.50 and 3.00 g/kg and a liquid formulation of Si as a foliar spray, i.e., of 0.0, 0.8, 1.7 and 3.4 ppm were tested to study their effect on the development of FHB fungi on two barley moderately resistant “MR” and susceptible “S” cultivars. Results: All concentrations of Si did not significantly reduce DI and DS at 7 dpi. The disease reduction was observed with the application of 1.50 g/kg of soil and 1.7 ppm at 14 dpi and increased with time until 28 dpi, however, the other rates had no significant effect. At 28 dpi, solid and foliar treatments reduced DI by 26.6% and 22.9%, respectively, on “MR” cultivar, and by 19.4% and 19.5%, respectively, on “S” cultivar and decreased DS by 20.4% and 19.5%, respectively, on “MR” plants and by 18.8% and 18.4%, respectively, on “S” plants. Conclusion: No effects of Si were observed during the initial infection stage; our results suggest that Si triggers defense processes in barley plants in the latest infection stages to diminish DI and DS by affecting mycotoxins synthesis. Si inputs can be a valuable tool in integrated FHB management by reducing the disease development on barley.

Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.