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Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6–10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes. [ABSTRACT FROM AUTHOR]

This paper critically examines Pakistan's sports policy, from the design, development and delivery phases through to its public evaluation. In doing so, we identify and address the emerging trends and associated challenges facing sports organisations in a large politically unstable developing nation. Ten interviews and an analysis of over 15 policy documents, including annual reports, were conducted over the three-year period 2019–2021. This critical case study documents the sport-politics nexus in Pakistan, including the ongoing impact of the 2011 18th constitutional amendment on sport. The key conclusions from this study are that the development and delivery of sport policy, at both a domestic and international level, was negatively affected by administrative inefficiencies in organisational structures and the devolution of the Pakistan Sports Board. A lack of public and private sector investment and an unjust distribution of funds were also found to have hindered the nation's ability to use sport as a vehicle for socio-economic development and soft power projection. In sum, Pakistan's sports policy and underlying structures fall short of modern international sports requirements, and reform is strongly recommended. [ABSTRACT FROM AUTHOR]

Plant oils are very important for domestic and industrial use. Biodiesel can be obtained from plant seed oil. Biodiesel is currently popular and in demand due to the high cost of petroleum and to avoid pollution. It is time to increase plant seed oil production and conduct research to find ways of enhancing its production. We studied two species of oil seed plants, i.e. Ricinus communis and Glycine max, with varying amounts of oil content. Proteins from six categories of enzymes involved in fatty acid biosynthesis were selected for study. The 3D structures were predicted using different structure prediction tools. The structures were validated and selected on the basis of quality factors. The pairs of proteins were compared by pairwise sequence alignment using Clustal W and structural superposition by Chimera Matchmaker. The physiochemical properties were studied by PROTPARAM. In R. communis, eighteen structures were selected from I Tasser, thirteen from Swiss Model, and two from Raptorx. In G. max, twenty structures were selected from I Tasser, nine from Swiss Model, and four from Raptorx. The highest percent identity in pairwise sequence alignment was observed between the two species for biotin carboxylase. Biotin carrier was least identical between these two species. Monogalactosyldiacylglycerol desaturase (FAD5) showed the highest percentage of structural identity between the two species while ER phosphatidate phosphate was least identical. Eight proteins in both species had an instability index below 40. Eight proteins in R. communis and five in G. max were acidic in nature. Fourteen proteins in R. communis and seventeen in G. max were hydrophobic. The aliphatic index of all proteins was above 50 with which conferes good thermal stability. [ABSTRACT FROM AUTHOR]