Preparation of Cocoa Powder-Containing Orally Disintegrating Tablets of Rebamipide (Rebamipide Chocolet) and Evaluation of Their Clinical Palatability

Abstract

Orally disintegrating tablets (ODTs), which are administered without water, are beneficial for elderly patients and patients with dysphagia. Masking the unpleasant taste of a drug is an important factor associated with adherence of patients consuming ODTs. We prepared cocoa powder-containing ODTs of bittertasting rebamipide (rebamipide chocolet) and evaluated their clinical palatability. We prepared rebamipide ODTs by adding a sweetener and 0, 2.5, 5, and 10% cocoa powder (Ch0-ODTs, Ch2.5-ODTs, Ch5-ODTs, and Ch10-ODTs, respectively). Rebamipide ODTs without cocoa powder and sweetener were used as controls (Cont-ODTs). We performed a gustatory sensation test in 30 healthy adult volunteers. We used the 100-mm visual analog scale (VAS) to evaluate bitterness, sweetness, scent, and overall palatability of the ODTs. The acceptability of each ODT was evaluated on a 5-point scale. Compared to Cont-ODTs, Ch0-ODTs showed no significant improvement in the VAS score for bitterness, scent, and overall palatability during disintegration. However, compared to Cont-ODTs, Ch2.5-ODTs, Ch5-ODTs, and Ch10-ODTs showed an improvement in all items evaluated using the VAS. In particular, Ch2.5-ODTs showed a significant improvement compared to the Cont-ODTs in the VAS score of all items. Evaluation on a 5-point scale indicated that Ch2.5-ODTs and Ch10-ODTs had the highest acceptability. We prepared rebamipide chocolet with excellent palatability properties, which could not be achieved using a sweetener alone, by using the combination of a sweetener and cocoa powder as a new agent for masking bitterness. Our results indicate that cocoa powder may be used as a taste-masking agent in ODTs.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability

“…Previous studies showed that using the VAS score in human gustatory sensation tests is an appropriate method to quantitatively evaluate the palatability of several oral formulations. [14][15][16][17][18][19] VAS is widely used for assessing the levels of pain or palatability in human subjects and is regarded as a reproducible approach that provides a good representation of subjective measurements. 20) The median VAS scores for the bitterness of azithromycin in the first and second evaluations are shown in Figs.…”

“…Previously, our group also investigated the palatability of the physical and organoleptic taste-masked orally disintegrating tablet of famotidine and amlodipine, and evaluated the predictability of human gustatory sensation by the a-Astree electronic gustatory test. 14) Although electronic gustatory systems can reduce potential ethical concerns about taste assessments of medicinal products as the absolute number of samples used in human gustatory sensation tests may be reduced, the prediction of palatability using electronic gustatory systems cannot replace human gustatory sensation tests. Especially overall palatability is including taste/after taste, somatosensory modalities such as touch (texture), grittiness, astringency, temperature, cooling effect, appearance even sound and smell.…”

Strategies for Taste Masking of Orodispersible Dosage Forms: Time, Concentration, and Perception

“…In addition, some other substances are supplementary to assist taste masking, including flavoring agents, off-taste masking, and oral paralysis agents. Flavoring agents refer to substances that make drugs taste better by stimulating olfactory and saliva secretion, often used with sweeteners . The choice of flavors is based on the taste of the drug, such as strawberry and orange flavors suitable for sour medicines, coffee and chocolate suitable for bitter drugs, and grape and mint, ideal for the metallic drug .…”

“…Flavoring agents refer to substances that make drugs taste better by stimulating olfactory and saliva secretion, often used with sweeteners. 161 The choice of flavors is based on the taste of the drug, such as strawberry and orange flavors suitable for sour medicines, coffee and chocolate suitable for bitter drugs, and grape and mint, ideal for the metallic drug. 162 Off-taste masking agents are chemicals to eliminate the unpleasant aftertaste of all sweeteners by simply adding to or mixing with drugs.…”

Pharmacological and clinical feature of rebamipide: new therapeutic targets

“…Чтобы избежать горечи, препарат покрыт пленочной оболочкой. Японскими фармацевтами разрабатываются перорально растворимые таблетки с какао-порошком, удобные для пациентов с дисфагией [4].…”