Multi-Methodological Quantitative Taste Assessment of Anti-Tuberculosis Drugs to Support the Development of Palatable Paediatric Dosage Forms

Abstract

The unpalatability of antituberculosis drugs is often cited as a major cause of non-adherence in children, yet limited quantitative taste assessment data are available. The aim of this research was to quantify the bitterness of isoniazid, rifampicin, pyrazinamide, and ethambutol dihydrochloride using two in vivo (a human taste panel and a rat brief-access taste aversion (BATA) model) and one in vitro (sensor) method. The response of the Insent TS-5000Z electronic tongue was compared to the in vivo drug concentration found to elicit and suppress half the maximum taste response (EC50 in human and IC50 in rats). Using dose-relevant concentrations, an overarching rank order of bitterness was derived (rifampicin > ethambutol > pyrazinamid~isoniazid). In vitro, only ethambutol exhibited a linear response for all sensors/concentrations. Based on the EC50/IC50 generated, a ‘taste index’ was proposed to allow for anticipation of the likelihood of taste issues in practice, taking in account the saturability in the saliva and therapeutic doses; ethambutol and isoniazid were found to be the worst tasting using this measure. The study presents the first quantitative taste analysis of these life-saving drugs and has allowed for a comparison of three methods of obtaining such data. Such information allows the operator to identify and prioritise the drugs requiring taste masking to produce palatable formulations.

Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?

“…The dosage form of choice should address the problems of palatability, ease of swallowing, safety, good quality, and affordability. Other vital factors that can be considered for optimal pediatric TB drug formulation include: (i) children’s vulnerability during clinical trials; (ii) challenges associated with effective taste-masking, particularly for oral dosage forms; (iii) limitations related to the types of excipients that can be safely used; and (iv) the lack of suitable manufacturing technologies specific for making such specialized formulations [ 227 , 229 ].…”

“…This can be attributed to the fact that the market for pediatric dosage forms is relatively small, risky, and less profitable than that for adult pharmaceutical formulations [ 213 , 227 ]. Further, the development of age-appropriate, anti-TB pharmaceutical formulations for children is challenging because of the differences in their developmental stages and effective taste masking problems, which greatly impacts compliance as well as limitations surrounding safe excipient selection and large-scale manufacturing [ 223 , 226 , 229 ]. The most commonly available branded dosage forms for TB treatment in pediatrics include oral solutions, suspensions, and single and fixed-dose combination solid dosage forms [ 215 , 218 , 230 , 239 ].…”

Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery

“…If more than ± 5 mV is recorded by the sensors, this implies that the drug displays this taste quality to some degree. BT0 is the newest basic bitterness sensor with improved selectivity and sensitivity [53] and therefore data from it was used for comparisons. Figure 11 shows BT0 s response as initial taste and aftertaste output (CPA) to raw CPM at concentrations ranging between 0.01 to 10 mM, to ensure detectability.…”

Assessing physical and chemical properties of saliva among tuberculosis patients on anti-tuberculosis treatment - An observational study

“…The standard treatment regimen lasts a minimum of six months. Tuberculosis patient take three or four drugs, typically isoniazid, rifampicin, pyrazinamide, and ethambutol dihydrochloride, in combination for two months (intensive phase), followed by rifampicin and isoniazid for four months (continuation phase) [1] .…”

“…Anti-tuberculosis drugs affect the taste, smell, or salivation and lead patients to change their patterns of food or fluid intake. This may lead to nutritional deficiencies, loss of appetite, and weight loss resulting in some other diseases [1] , [5] , [6] . Therefore, predictably these may cause some physical and chemical changes in the saliva of these patients.…”