Evaluation of the losartan solubility in the biowaiver context by shake-flask method and intrinsic dissolution

This study aimed at evaluating the shake-flask use as a universal method to evaluate drug solubility in a biowaiver context as proposed by FDA, EMA and ANVISA. The solubility of losartan was determined in three buffers using the shake-flask method, intrinsic dissolution (ID) and Quantum Chemistry. Moreover, the evaluation of a losartan dissolution profile from coated tablets was conducted. The losartan low solubility in pH 1.2 and high solubility in pH 6.8 were observed using the shake-flask method. However, the solubility results using ID demonstrated its high solubility in pH 1.2 and 6.8. It was not possible to find conclusive results regarding the solubility of the drug in pH 4.5. The studies conducted by Quantum Chemistry provide molecular and electronic data that helped understand the losartan solvation in different pH values. Our experimental results defined that losartan can be classified as a low-solubility drug. In addition, this work shows that shake-flask cannot be a universal method of solubility studies in biowaiver context. Individual analysis will be necessary. The intrinsic dissolution should be considered as a complementary method.     

Effects of psychosocial stimulation on improving home environment and child-rearing practices: results from a community-based trial among severely malnourished children in Bangladesh

ABSTRACT: BACKGROUND: Parenting programmes are effective in enhancing parenting practices and child development. This study evaluated the effects of a intervention with psychosocial stimulation (PS) on the quality of the home environment and mothers' child-rearing practices in a community-based trial with severely malnourished Bangladeshi children. METHOD: Severely underweight children (n = 507), 6-24 months of age, were randomly assigned to five groups: PS; food supplementation (FS); PS + FS; clinic-control (CC); and, hospital-control (CH). PS included fortnightly follow-up visits for six months at community clinics where a play leader demonstrated play activities and gave education on child development and child rearing practices. FS comprised cereal-based supplements (150-300 kcal/day) for three months. All groups received medical care, micronutrient supplements and growth monitoring. Mothers were given the Home Observation for Measurement of the Environment (HOME) inventory and a questionnaire on parenting at baseline and after six months to assess the outcome. RESULTS: 322 children completed the study. After six months of intervention the PS + FS and PS groups benefitted in the total HOME score (depending on the comparison group, effect sizes varied from 0.66 to 0.33 SD) The PS + FS and PS groups also benefitted in two HOME subscales: maternal involvement (effect sizes: 0.8 to 0.55 SD) and play materials, (effect sizes: 0.46 to 0.6 SD), and child-rearing practices scores (effect size: 1.5 to 1.1 SD). The PS + FS group benefitted 4.0 points in total HOME score compared with CH, 4.8 points compared with CC and 4.5 points compared with FS (p < 0.001 for all). The PS group benefitted 2.4 points compared with CH (p = 0.035), 3.3 points compared with CC (p = 0.004), and 2.9 points compared with FS (p = 0.006). Child-rearing practice scores of the PS + FS group improved 7.7, 6.4 and 6.6 points and the PS group improved 8.5, 7.2 and 7.4 points more than CH, CC and FS, respectively (p < 0.001 for all). CONCLUSIONS: Child-rearing practices of mothers of severely malnourished children and the quality of their home environment can be improved through community-based psychosocial stimulation with or without food supplementation. This may be of importance to promote child development.     

Quasi-reversible two-electron reduction of oxygen at iodine submonolayer-coated gold electrode in alkaline media

Oxygen reduction reaction (ORR) was investigated using polycrystalline gold (Au (poly)) electrode modified with chemisorbed iodine (I_(ads)) submonolayer (sub I_(ads)) in O₂-saturated 0.1 M KOH solution. The sub I_(ads) was tailored by potential-dependent partial reductive desorption of I_(ads) from its full monolayer. The Au (1 1 1) facet of the Au (poly) electrode was considered to remain bared at the sub I_(ads)/Au (poly) electrode. The interesting finding of the present study is that (unlike the bare Au (poly) electrode) the sub I_(ads)/Au (poly) electrode exhibited a quasi-reversible two-electron reduction of O₂ in alkaline media. The probable origin of the observed quasi-reversible behavior of the ORR is discussed. Experimental investigations were performed using cyclic and steady-state voltammetric, amperometric and coulometric techniques.