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%).     

Antistress Activity of Tinospora cordifolia and Centella asiatica Extracts

Tinospora cordifolia Miers. and Centella asiatica Linn. were screened for their putative antistress activity in a battery of experiments. Ethanol extracts of both drugs at 100 mg/kg exhibited significant antistress activity in all the parameters studied, compared with diazepam at 2.5 mg/kg.     

Correction: Realization of multi-configurable logic gate behaviour on fluorescence switching signalling of naphthalene diimide congeners

Correction for ‘Realization of multi-configurable logic gate behaviour on fluorescence switching signalling of naphthalene diimide congeners’ by Hridoy Jyoti Bora et al., RSC Adv., 2021, 11, 35274–35279. DOI: 10.1039/d1ra06728a.

The authors regret that there was an error in the sentence in lines 24–27 in the left column on page 35278 of the original article. The text originally read, “Mass spectrometric data Shimadzu UV-Vis spectrophotometer, UV-2600 is used to record the absorption spectra were gained from a THERMO 3000 Exactive Plus Orbitrap Mass Spectrometer”. This sentence should read, “Mass spectrometric data were gained from a THERMO 3000 Exactive Plus Orbitrap Mass Spectrometer. Shimadzu UV-Vis spectrophotometer, UV-2600 is used to record the absorption spectra”.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Newer variants of progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders characterized by defects in bile secretion and presentation with intrahepatic cholestasis in infancy or childhood. The most common types include PFIC 1 (deficiency of FIC1 protein, ATP8B1 gene mutation), PFIC 2 (bile salt export pump deficiency, ABCB11 gene mutation), and PFIC 3 (multidrug resistance protein-3 deficiency, ABCB4 gene mutation). Mutational analysis of subjects with normal gamma-glutamyl transferase cholestasis of unknown etiology has led to the identification of newer variants of PFIC, known as PFIC 4, 5, and MYO5B related (sometimes known as PFIC 6). PFIC 4 is caused by the loss of function of tight junction protein 2 (TJP2) and PFIC 5 is due to NR1H4 mutation causing Farnesoid X receptor deficiency. MYO5B gene mutation causes microvillous inclusion disease (MVID) and is also associated with isolated cholestasis. Children with TJP2 related cholestasis (PFIC-4) have a variable spectrum of presentation. Some have a self-limiting disease, while others have progressive liver disease with an increased risk of hepatocellular carcinoma. Hence, frequent surveillance for hepatocellular carcinoma is recommended from infancy. PFIC-5 patients usually have rapidly progressive liver disease with early onset coagulopathy, high alpha-fetoprotein and ultimately require a liver transplant. Subjects with MYO5 B-related disease can present with isolated cholestasis or cholestasis with intractable diarrhea (MVID). These children are at risk of worsening cholestasis post intestinal transplant (IT) for MVID, hence combined intestinal and liver transplant or IT with biliary diversion is preferred. Immunohistochemistry can differentiate most of the variants of PFIC but confirmation requires genetic analysis.     

Chondromyxoid fibroma: A fine-needle aspiration diagnosis

A 25-yr-old female presented with a slowly progressive swelling, occurring over an 8-yr period, in the right lower leg. The swelling was tender and fixed to the underlying bone. Clinical and radiological diagnosis was giant cell tumor (GCT) of the bone. Aspiration cytology smears were cellular showing an admixture of chondroid, stellate, and fibrocytic cells against a chondroid background. On cytomorphology, a diagnosis of chondromyxoid fibroma (CMF) was made. It was confirmed on histologic examination.