Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling

Suzuki, Hiroyuki; Onishi, Hiraku; Hisamatsu, Seiji; Masuda, Kenji; Iwata, Masanori; Machida, Yoshiharu

doi:10.1016/j.ijpharm.2004.02.031

Cited by 43 publications

(18 citation statements)

References 19 publications

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“…24,25) The commercially available, orally disintegrating tablet, Gaster ® D is also developed and easily taken without water and is therefore suitable for elderly patients with diminished swallowing ability. As mentioned in the previous section, the channel 8 sensor is responsive to sweeteners, whereas famotidine elicits a high response from channel 3, which is responsive to bitterness.…”

Section: Methods 1 For the Evaluation Of Bitterness-suppressionmentioning

confidence: 99%

The Quantitative Prediction of Bitterness-Suppressing Effect of Sweeteners on the Bitterness of Famotidine by Sweetness-Responsive Sensor

Hashimoto

Matsunaga

Tokuyama

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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Famotidine, a histamine-2 receptor antagonist, is widely available as a treatment for gastric ulcers. The bitterness of famotidine is the main obstacle to good compliance for this medicine; the drug is frequently administered as an orally disintegrating tablet so that high concentrations of famotidine are delivered directly into the mouth. Therefore the quantitative evaluation of the effect of various sweeteners such as sugar alcohols, which are included in the formulation, on the bitterness-suppression of famotidine seems so important. Hashimoto et al. provided in Japanese Patent No. 2705787 1) that sugar alcohols suppress famotidine's bitterness. But it's not desirable to examine a bitterness-suppression by human repeatedly. If an alternative method is found, without exposures of famotidine or any medicine, more bitterness-suppression formulations are able to be produced easily and safely.Some articles reported on the quantitative evaluation of the bitterness of medicines, amino acids and elemental diets using the artificial taste sensor.2-4) The sensor was also successful in evaluating or predicting the bitterness-suppression of quinine hydrochloride by phospholipids, [5][6][7][8] which suppress bitterness by selectively competing at the bitterness receptor, or by adsorbing and coating the bitter substances. This result demonstrated that it is possible to predict the bitterness-suppression of human medicines at peripheral site (receptor sites in human taste cells) using the sensor's response to bitterness. However, it has been more difficult for the sensors to predict bitterness-suppression by sweet substances, 6) since bitterness-suppression seems to occur during the process of neurotransmission, which means the central bitterness-suppression. It also has been reported that the receptors for bitterness and for sweetness are different. 9-15)Therefore a sensor which responds to bitterness would be unable to evaluate bitterness-suppression by sweet substances.The purpose of the present study was to develop a quantitative prediction method for the bitterness-suppressing effect of sweeteners (sucrose and several sugar alcohols) on famotidine solutions, and also to examine the bitterness intensity of commercially available, orally disintegrating tablets containing famotidine, using the artificial taste sensor.Firstly, we characterized this newly developed sweetnessresponsive sensor 16) for sweet-tasting substances such as sucrose and sugar alcohol solutions. We found that the negative output values of the various sweeteners became larger as the sweetener concentrations increased. Secondly, we used two different methods (indirect and direct) for the quantitative evaluation of bitterness-suppression, and demonstrated the usefulness of the sweetness-responsive sensor in this evaluation. In both methods, we tried to evaluate bitterness-suppression of famotidine or quinine sulfate solution by using obtained sensor output of unknown concentrated sucrose or sugar alcohols. We fixed the concentrations of famotidine (1 ...

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Section: Methods 1 For the Evaluation Of Bitterness-suppressionmentioning

confidence: 99%

The Quantitative Prediction of Bitterness-Suppressing Effect of Sweeteners on the Bitterness of Famotidine by Sweetness-Responsive Sensor

Hashimoto

Matsunaga

Tokuyama

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Recent studies have reported that more than a half of the interviewed patients with schizophrenia (n = 400) preferred orally disintegrating tablets (ODT) to other dosage forms, such as tablets, for swallowing or oral delivery. [5][6][7] In this sense, other forms of delivery, such as the use of chewable or dissolvable tablets, [8][9][10] or rapidly dissolving films, [11][12][13] could be advantageous; however, these forms must be preceded by the development of taste-masking formulations, owing to the unpleasant taste of APZ. Numerous approaches have been employed in the field of taste masking, most of which were have been based on the encapsulation of drugs inside polymeric materials, such as hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Abstract: Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively.…”

Section: Introductionmentioning

confidence: 99%

AripiprazoleMontmorillonite: A New Organic–Inorganic Nanohybrid Material for Biomedical Applications

Choi

Choy

et al. 2013

Chemistry A European J

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Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively. Herein, we prepared a nanohybrid system that was based on a bentonite clay material, montmorillonite (MMT), which could both mask the taste and enhance the solubility of APZ (i.e., APZ-MMT). To further improve the efficacy of this taste masking and drug solubility, APZ-MMT was also coated with a cationic polymer, polyvinylacetal diethylamino acetate (AEA). In vitro dissolution tests at neutral pH showed that the amount of drug that was released from the AEA-coated APZ-MMT was greatly suppressed (<1%) for the first 3 min, thus suggesting that AEA-coated APZ-MMT has strong potential for the taste masking of APZ. Notably, in simulated gastric juice at pH 1.2, the total percentage of APZ that was released within the first 2 h increased up to 95% for AEA-coated APZ-MMT. Furthermore, this in vitro release profile was also similar to that of Abilify®, a commercially available medication. In vivo experiments by using Sprague-Dawley rats were also performed to compare the pharmacokinetics of AEA-coated APZ-MMT and Abilify®. AEA-coated APZ-MMT exhibited about 20% higher systemic exposure of APZ and its metabolite, dehydro-APZ, compared with Abilify®. Therefore, a new MMT-based nanovehicle, which is coated with a cationic polymer, can act as a promising delivery system for both taste masking and for enhancing the bioavailability of APZ.

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“…Various efforts have been made to improve medication adherence, [1][2][3] because it is a complex, multi-determined behavior that is often influenced by the cost of treatment, drug regimen complexity, and patient-related factors. Optimized dosage forms for each patient, such as orally disintegrating tablets, 4,5) oral jelly formulations, 6) chewable tablets, 7,8) and gummi formulations, [9][10][11] have important roles in medication adherence. Gummi drugs are dried jelly drugs prepared by adding gelatin as a gelling agent to syrup, consisting of carbohydrates such as sugar and starch syrup that have been boiled down.…”

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confidence: 99%

Palatability and Preference of Gummi Formulations with Various Pharmaceutical Characteristics

Nakagaki

Uchida

Tanaka

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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This study aimed to elucidate the appropriate physical characteristics that are clinically acceptable for gummi formulations. We prepared 11 placebo gummi formulations containing different amounts of gelatin and water and evaluated their penetration and restitution using a penetrometer and rheometer, respectively. Clinical sensory tests in 16 healthy volunteers (age, 23.4 0.9 years, mean standard deviation) were conducted on the placebo gummi formulations using the visual analog scale (VAS) score to evaluate elasticity, hardness, and overall palatability, with a 5-point rating scale of preference. The penetration increased with decreasing amounts of gelatin or increasing amounts of water in the gummi formulations. Similarly, the VAS score of elasticity and hardness from the clinical sensory tests increased with increasing amounts of gelatin but decreased with increasing amounts of water. The relationship between the penetration and VAS scores of elasticity and hardness revealed good linear correlations. This suggests that the penetration was well reflected by the hardness results of the clinical VAS scores. The overall palatability evaluated using the VAS score increased until the penetration was 10 mm and then plateaued at >10 mm penetration. The 5-point rating score for preference revealed that >50% of volunteers "prefer" the gummi formulations with penetration values of 9.8 to 13.5 mm. These results suggest that gummi formulations likely have an appropriate window of hardness. Furthermore, appropriate gummi formulations with clinically preferred physical characteristics could be prepared by adjusting the amount of gelatin and water and measuring their penetration.

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Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling

Cited by 43 publications

References 19 publications

The Quantitative Prediction of Bitterness-Suppressing Effect of Sweeteners on the Bitterness of Famotidine by Sweetness-Responsive Sensor

The Quantitative Prediction of Bitterness-Suppressing Effect of Sweeteners on the Bitterness of Famotidine by Sweetness-Responsive Sensor

AripiprazoleMontmorillonite: A New Organic–Inorganic Nanohybrid Material for Biomedical Applications

Palatability and Preference of Gummi Formulations with Various Pharmaceutical Characteristics

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