Taste evaluation of a novel midazolam tablet for pediatric patients: In vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles

[Display omitted] [Display omitted] Harmonized methodologies are urgently required for the taste evaluation of novel pediatric medicines. This study utilized in vitro, in vivo and clinical data to evaluate the palatability of a novel midazolam chocolate tablet. In vitro dissolution experiments showe...

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Bibliographic Details
Published in:International journal of pharmaceutics 2018-01, Vol.535 (1-2), p.194-200
Main Authors: Cheung, Laurence C., Nguyen, Minh, Tang, Edith, von Ungern Sternberg, Britta S., Salman, Sam, Tuleu, Catherine, Mohamed Ahmed, Abeer H.A., Soto, Jessica, Lim, Lee Yong
Format: Article
Language:English
Subjects:
Administration, Oral
Adolescent
Animals
Child
Child, Preschool
Chocolate
Drug Compounding
Drug Liberation
Facial Expression
Feeding Behavior - drug effects
Flavoring Agents - chemistry
Humans
Hypnotics and Sedatives - administration & dosage
Hypnotics and Sedatives - chemistry
Injections, Intravenous
Male
Midazolam
Midazolam - administration & dosage
Midazolam - chemistry
Pediatric formulations
Prospective Studies
Rats, Sprague-Dawley
Tablets
Taste
Taste Perception - drug effects
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Summary:[Display omitted] [Display omitted] Harmonized methodologies are urgently required for the taste evaluation of novel pediatric medicines. This study utilized in vitro, in vivo and clinical data to evaluate the palatability of a novel midazolam chocolate tablet. In vitro dissolution experiments showed the crushed tablet to release within 5 min 1.68 mg of midazolam into simulated saliva. This translated to a drug level of 0.84 mg/ml in the oral cavity, which would be higher than the midazolam bitterness detection threshold concentration of 0.03 mg/ml determined in a rat ‘brief access taste aversion’ (BATA) model. The visual analogue scale scores of patients aged 4–16 years prescribed with midazolam pre-surgery showed a clear preference for the midazolam chocolate tablets (3.35 ± 1.04, n = 20) compared to the control midazolam solution (1.47 ± 0.62, n = 17). The clinical data was in agreement with the in vivo rodent data in showing the novel chocolate tablet matrix to be effective at taste-masking the bitter midazolam.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.10.060