A Proposed Methodology for In Vitro Evaluation of Bitterness in Drug Solutions and In Vitro Drug Release Samples

Purpose

Ethical and safety concerns, paediatric taste panels and predictivity in early drug development for strategic decisions are some of the reasons for seeking in vitro methods of bitterness evaluation for drugs and drug products. In this study, taste panel studies and in vitro drug release studies have been performed, correlated to each other and proposed as an analytical tool for evaluation of bitterness.

Methods

Bitterness threshold and bitterness scores for different solutions of ondansetron hydrochloride (ONS) were estimated by taste panel studies. In vitro drug release studies on taste-masked drug product in pharmacopoeial apparatus and an in-house-developed apparatus were performed and correlated to drug release studies in oral cavity.

Results

Concentration of 22 μg/ml and below was perceived bitterless by all the volunteers of taste panel. A second-order polynomial equation (y?=?0.6206x ²???0.2011x???0.7796; correlation coefficient R ²?=?0.991) was derived as a relationship between bitterness score and log ONS concentration. Drug release in in-house-assembled apparatus and oral cavity were not statistically different (α?=?0.05) at both 60 and 120 s.

Conclusions

Bitterness threshold and bitterness scores are helpful in evaluation of bitterness in drug solutions and samples obtained from drug release studies.     

Equine trypanosomosis in central and western Punjab: Prevalence,haemato-biochemical response and associated risk factors

The detection of Trypanosoma evansi in blood is intricate, primarily in chronic stage of infection, as the parasitaemia is often low and fluctuating. The climatic conditions of the target area of Punjab (a province of India with a total of 34,000 horses and ponies used for sports and transport) are conducive for the parasite propagation. The objective of present investigation was to assess the prevalence of T. evansi in central and western Punjab by PCR and card agglutination test (CATT/T. evansi) in relation to clinico-haematobiochemical alterations and risk factors associated with latent trypanosomosis. A total of 169 equine blood and serum samples tested by CATT/T. evansi revealed 16 cases positive, with 6.8% from central plain and 13.63% from western zone. To assess the specificity of serological test, PCR₁ was performed using established primer pair TR3 5′-GCG CGG ATT CTT TGC AGA CGA-3′ and TR4 5′-TGC AGA CAC TGG AAT GTT ACT-3′ for T. evansi. PCR₂ applied with primer pair RoTat1.2F: 5′-ATG TCA ACG ATG CCT GTT ACA TTA CGC AC-3′ and RoTat1.2R: 5′-TAA ATA TCA CTG TCA AGA CCT GCT GCG G-3′ to rule out the consensus between the finding of the two PCR assays and agglutination test for T. evansi, which displayed results in concordance with PCR₁. PCR assays showed 1.92 and 1.51% positive samples from central plain and western zone, respectively. With respect to PCR assay, CATT/T. evansi showed 100% sensitivity and 92.1% specificity. Microscopy showed a very low prevalence rate of 0.59% with only one sample positive with teaming parasitaemia. Comparison between sexes revealed higher positivity in mares by the three tests (BSE: 0.95%, PCR: 2.88%, CATT/T. evansi: 14.42%). The haemato-biochemical factors were found to be altered in PCR positive cases, while the mean value of vital parameters lied in normal range in seropositive cases. The female horse (RR = 0.0937, 95% CI = 1.388–190.223%) population was found to be at the highest risk of seropositivity for T. evansi, particularly in the unorganized farms (RR = 19.726, 95% CI = 2.918–400.221%).     

Concurrent balloon dilatation of tricuspid and calcific mitral valve in a patient of rheumatic heart disease

Concurrent percutaneous balloon dilatation of the mitral and tricuspid valve was performed in a 21-year-old female with severe rheumatic calcific mitral stenosis and severe tricuspid stenosis. The mean gradient across the mitral valve decreased from 30 mm Hg to an immediate post-dilatation level of 14 mm Hg and the mitral valve area increased from 0.71 cm2/m2 to 1.2 cm2/m2. The mean gradient across the tricuspid valve decreased from 11.5 mm Hg to 5 mm Hg. Hemodynamic improvement was maintained at a repeat study performed eight days later. Palliative balloon dilatation of two valves, concurrently performed, thus saved the patient from an open heart procedure and a possible valve replacement.     

Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens

We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis.     

Assessment of an irritant gas plume model for epidemiologic study

Previously, we reported the development of a Hazard Prediction and Assessment Capability plume dispersion model of the 2005 Graniteville, South Carolina, USA accidental release of chlorine. Here, we assess this model by spatial and statistical comparison with post-incident observed environmental indicators of exposure and other types of observations. Spatial agreement was found when the model was compared to phytotoxic bleaching and corrosion events observed in 2 km radius around the release site. When spatially compared to locations of injured or killed animals, model predictions of the plume footprint were in relatively good agreement. Model-predicted human casualties differed from observed casualty counts primarily due to the shielding effect of buildings. A statistical comparison of observed dog health outcome-derived exposure vs. model predicted exposure showed relatively good agreement, particularly when a subcohort of indoor dogs was excluded. Evaluation and assessment of the building infiltration effect would further improve the model prior to application in epidemiologic study.