Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets

• Published in: Biological & pharmaceutical bulletin Vol. 40; no. 4; pp. 451 - 457
• Main Authors: Sotoyama, Mai, Uchida, Shinya, Tanaka, Shimako, Hakamata, Akio, Odagiri, Keiichi, Inui, Naoki, Watanabe, Hiroshi, Namiki, Noriyuki
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acids; Administration, Oral; Allergic rhinitis; Bitter taste; Bitterness; Citric acid; Citric Acid - administration & dosage; Dissolution; Drug Compounding; Female; Flavoring Agents - administration & dosage; Histamine H1 Antagonists, Non-Sedating - administration & dosage; Histamine H1 Antagonists, Non-Sedating - metabolism; human gustatory sensation test; Humans; Male; Olopatadine; Olopatadine Hydrochloride - administration & dosage; Olopatadine Hydrochloride - metabolism; orally disintegrating tablet; organoleptic masking; Palatability; Product development; Rhinitis; Saliva; Solubility; Tablets; Taste; Taste - drug effects; Taste - physiology; Yogurt; Young Adult
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b16-00828

Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid’s taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0–10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5–10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.