RESUMO
Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13-a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content-against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.
Assuntos
Candida albicans , Testes de Sensibilidade Microbiana , Oligopeptídeos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Candida albicans/efeitos dos fármacos , Conformação Proteica em alfa-Hélice , Propionibacteriaceae/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole-4,9-dione compounds (5a-e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a-e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole-4,9-dione skeleton and substituent effect, 5a-e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b-e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a-e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future.
Assuntos
Testes de Sensibilidade Microbiana , Tiazóis , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Staphylococcus/efeitos dos fármacos , Staphylococcus/crescimento & desenvolvimento , Estrutura Molecular , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologiaRESUMO
There is an urgent need to discover and develop novel antibacterial agents. Accordingly, we synthesised 2-(piperazin-1-yl)naphtho[2,3-d]thiazole-4,9-dione (PNT), which exhibits antimicrobial activity. The aim of this study was to characterise PNT as an effective antimicrobial agent. Fluorescence microscopy was used to measure PNT's uptake into microbial cells (strains of Staphylococcus epidermidis, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA)), transmission electron microscopy (TEM) was used to investigate the influence of PNT on the configuration of microbial cells, and a DNA gyrase supercoiling assay was used to investigate whether PNT inhibits DNA gyrase. PNT was taken up by more than 50% of microbial cells within 30 min. Using TEM, hollowed-out bacterial cytoplasms were observed in the specimen treated with PNT, although there was no disintegration of the bacterial membrane. In the DNA gyrase supercoiling assay, a dose-dependent reduction in fluorescence intensity was observed as the concentration of PNT increased. This suggests that PNT is taken up by microbial cells, resulting in cell disruption, and it reveals that one of the mechanisms underlying the antimicrobial activity of PNT is the inhibition of DNA gyrase.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus , Tiazóis/farmacologia , DNA Girase/genética , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The 1H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.
Assuntos
Flurbiprofeno , Paladar , Famotidina/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Ibuprofeno/farmacologia , NaproxenoRESUMO
The aim of this study was to evaluate bitterness by using "CCDP; Change in concentration-dependent potential" considering dose-dependency of active pharmaceutical ingredients (APIs) as new and useful bitterness evaluation index compared with bitter sensor output value which is conventional bitterness evaluation index for 48 pediatric medicines from the recent edition of the WHO model list of essential medicines for children (7th edn, 2019). Solutions (0.01, 0.03, 0.1 mM) of the compounds were evaluated by an artificial taste sensor using membranes sensitive to bitterness. The dose-response slope of the sensor outputs was defined as CCDP. On the basis of principal component analysis of CCDPs, chlorpromazine hydrochloride, amitriptyline hydrochloride, propranolol hydrochloride, primaquine phosphate and haloperidol were predicted to express the strongest levels of basic bitterness, surpassing that of quinine hydrochloride. Correlation analysis (Fisher's exact tests and multiple regression analysis) was performed to determine the relation between CCDPs and various physicochemical properties participated in hydrophilicity and hydrophobicity. It is revealed that contribution physicochemical factors are different by individual basic bitterness sensor (AC0, AN0 or BT0), and this result becomes the criterion of the sensor choice to evaluate basic bitterness intensity using basic bitterness sensors. Hydrophobic and hydrophilic interactions could be simulated by ligand docking modeling for haloperidol, miconazole and quinine hydrochloride. The pharmaceutical products need a bitterness evaluation in consideration of concentration-dependency to vary in a dose depending on a patient individual. Thus, it was concluded that CCDP correlated to hydrophilicity and hydrophobicity is useful as a bitterness evaluation index of APIs in pediatric medicines.
Assuntos
Técnicas Biossensoriais , Preparações Farmacêuticas/análise , Paladar , Criança , Humanos , Modelos MolecularesRESUMO
Diphenhydramine, a sedating antihistamine, is an agonist of human bitter taste receptor 14 (hTAS2R14). Diphenhydramine hydrochloride (DPH) was used as a model bitter medicine to evaluate whether the umami dipeptides (Glu-Glu and Asp-Asp) and their constituent amino acids (Glu, Asp) could suppress its bitterness intensity, as measured by human gustatory sensation testing and using the artificial taste sensor. Various concentrated (0.001-5.0 mM) Glu-Glu, Asp-Asp, Glu and Asp significantly suppressed the taste sensor output of 0.5 mM DPH solution in a dose-dependent manner. The effect of umami dipeptides and their constituent amino acids was tending to be ranked as follows, Asp-Asp > Glu-Glu >> Gly-Gly, and Asp > Glu >> Gly (control) respectively. Whereas human bitterness intensity of 0.5 mM DPH solution with various concentrated (0.5, 1.0, 1.5 mM) Glu-Glu, Asp-Asp, Glu and Asp all significantly reduced bitterness intensity of 0.5 mM DPH solution even though no statistical difference was observed among four substances. The taste sensor outputs and the human gustatory sensation test results showed a significant correlation. A surface plasmon resonance study using hTAS2R14 protein and these substances suggested that the affinity of Glu-Glu, Asp-Asp, Glu and Asp for hTAS2R14 protein was greater than that of Gly-Gly or Gly. The results of docking-simulation studies involving DPH, Glu-Glu and Asp-Asp with hTAS2R14, suggested that DPH is able to bind to a space near the binding position of Glu-Glu and Asp-Asp. In conclusion, the umami dipeptides Glu-Glu and Asp-Asp, and their constituent amino acids, can all efficiently suppress the bitterness of DPH.
Assuntos
Aminoácidos/farmacologia , Dipeptídeos/farmacologia , Difenidramina/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Paladar/efeitos dos fármacos , Aminoácidos/química , Dipeptídeos/química , Difenidramina/química , Relação Dose-Resposta a Droga , Humanos , Ligantes , Modelos Moleculares , Relação Estrutura-AtividadeRESUMO
The purpose of this study was to investigate the relationship between response to the bitterness taste sensor and physicochemical parameters of 47 pediatric medicines and to classify these medicines according to the biopharmaceutics classification system (BCS). Forty-seven bitter compounds, most of which were on the WHO model list of essential medicines for children (March 2017), were used in the study. Solutions (0.1 mM) were evaluated by an artificial taste sensor using membranes sensitive to bitterness. On the basis of principal component analysis of taste sensor measurements, chlorpromazine, haloperidol, propranolol, amitriptyline, diphenhydramine were predicted to express the strongest levels of basic bitterness, surpassing that of quinine. Correlation tests between bitter taste sensor outputs and physicochemical properties were then carried out and the compounds classified in terms of their biopharmaceutical properties. High log P values (≥2.82), physiological charge (≥1), low log S values (<-3) and small polar surface area (PSA; <45.59 Å2) were found to correlate significantly with the responses of bitter taste sensors. Forty-one of the 47 compounds could be placed into one of four groups in the BCS, on the basis of dose number (D0), an indicator of solubility which takes into account clinical dosage, and fractional absorption (Fa). For medicines classified in group 4, the factors D0 > 1 and Fa < 0.85 significantly correlated with the responses of the taste sensor for basic bitterness. It was concluded that lipophilicity, physiological charge, solubility, PSA and D0 are the main factors affecting the bitterness of pediatric medicines.
Assuntos
Técnicas Biossensoriais , Composição de Medicamentos , Paladar , Biofarmácia/classificação , Físico-Química , Criança , HumanosRESUMO
The purpose of the study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to evaluate physicochemical properties, its ease of swallowing using texture profile analysis (TPA) and its taste-masking effects on amlodipine besylate (AML) using the artificial taste sensor and human gustatory sensation testing. Using TPA, 0.5 and 1.0% (w/v) PGA gels in the absence of drug were within the range of acceptability for use in people with difficulty swallowing according to permission criteria published by the Japanese Consumers Affairs Agency. The elution of AML from prepared PGA gels was complete within an hour and the gel did not appear to influence the bioavailability of AML. The sensor output of the basic bitterness sensor AN0 in response to AML mixed with 0.5 and 1.0% PGA gels was suppressed to a significantly greater degree than AML mixed with 0.5 and 1.0% agar. In human gustatory sensation testing, 0.5 and 1.0% PGA gels containing AML showed a potent bitterness-suppressing effect. Finally, 1H-NMR spectroscopic analysis was carried out to examine the mechanism of bitterness suppression when AML was mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of AML shifted clearly upfield, suggesting an interaction between the amino group of AML and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations of AML, not only increasing ease of swallowing but also masking the bitterness of the basic drug.
Assuntos
Anlodipino/farmacologia , Hidrogéis/farmacologia , Ácido Poliglutâmico/análogos & derivados , Paladar/efeitos dos fármacos , Anlodipino/química , Humanos , Hidrogéis/química , Estrutura Molecular , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologiaRESUMO
The purpose of the study was to evaluate the ability of different beverages to mask the bitterness of zopiclone and eszopiclone in tablet formulations using the artificial taste sensor and human gustatory sensation testing. The beverages tested for bitterness-masking effects were: Mugicha, Sports beverage, Lactic acid drink, Orange juice and a diluted simple syrup (an 8.5% sucrose solution). The bitterness intensities estimated by the taste sensor of zopiclone or eszopiclone one-tablet solutions mixed with the various beverages, corresponded well with the observed bitterness intensities measured by gustatory sensation testing. The Sports beverage, Lactic acid drink and Orange juice significantly suppressed the bitterness intensity of both zopiclone and eszopiclone 1-tablet solutions compared with water when tested in the artificial taste sensor. Sports beverage, Lactic acid drink and Orange juice all contain citric acid as acidifier, so it was postulated that citric acid was involved in the mechanism of bitterness intensity suppression of zopiclone and eszopiclone 1-tablet solutions by these three beverages. It was then shown that citric acid suppressed the bitterness intensity of a zopiclone one-tablet sample solution in a dose-dependent manner. 1H-NMR spectroscopic analysis of mixtures of citric acid with zopiclone suggested that the carboxyl groups of citric acid interact with the amine group on zopiclone. This study therefore showed that the bitterness intensities of zopiclone and eszopiclone can be suppressed by citric-acid-contained beverages and suggests that this bitterness suppression is due to a direct electrostatic interaction between citric acid and the two drugs.
Assuntos
Compostos Azabicíclicos/metabolismo , Bebidas , Zopiclona/metabolismo , Hipnóticos e Sedativos/metabolismo , Piperazinas/metabolismo , Paladar/efeitos dos fármacos , Adulto , Ácido Cítrico/metabolismo , Feminino , Humanos , Comprimidos , Adulto JovemRESUMO
The purpose of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres (MS) loaded with itraconazole (ITCZ) or miconazole (MCZ) under different evaporation temperatures (25 or 40°C) using an oil-in-water emulsion solvent evaporation method in order to evaluate the initial burst release of drug. Loading efficiencies were comparatively good and the diameters of prepared drug-loaded PLGA MS were around 20 µm in all formulations. The release rates of ITCZ-PLGA MS prepared at 40°C showed a significantly restricted release profile compared with the corresponding ITCZ-PLGA MS prepared at 25°C. This difference in release rate of ITCZ was thought to be caused by the self-healing effect of PLGA, as the glass transition temperature of PLGA is around 40°C. With respect to the MCZ-PLGA MS, the initial burst release was similar in formulations prepared at both 25 and 40°C. Scanning electron microscope results suggested that the initial burst release was due to the localization of MCZ on the surface of MCZ-PLGA MS at higher concentrations. Differential scanning calorimetry measurements suggested complete amorphization of MCZ in MCZ-PLGA MS, whereas crystalline ITCZ was detected in the ITCZ-PLGA MS. This complete amorphization of MCZ is considered to be one of the reasons for the initial burst release.
Assuntos
Portadores de Fármacos/química , Itraconazol , Miconazol , Microesferas , Poliglactina 910 , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Itraconazol/química , Miconazol/químicaRESUMO
The purpose of this study was to examine the ability of the artificial taste sensor to evaluate the bitterness of drugs by comparing the responses of the taste sensor with documented responses of human TASTE2 receptors (hTAS2Rs). For this purpose 22 bitter compounds, used as ingredients of pharmaceutical medicines in Japan and known ligands of hTAS2Rs, were selected for testing. Their solutions (0.01, 0.03, 0.1 mM) were evaluated by five different taste sensors (AC0, AN0, BT0, C00, AE1). Correlations between physicochemical parameters of the compounds and the responses of the taste sensors and hTAS2Rs were evaluated. From taste sensor measurements, diphenidol, haloperidol, diphenhydramine, dextromethorphan and papaverine, all ligands of hTAS2R 10 and/or hTAS2R14, were predicted to express strong bitterness, surpassing that of quinine. Responses of taste sensors BT0 were found to be significantly correlated with responses of hTAS2R14. High log P values (â§2.73) and responses of hTAS2R14 were also significantly correlated (** p<0.01, chi-square test). In conclusion, taste sensor BT0 is highly sensitive to bitterness and correlates significantly with hTAS2R14, making it useful for evaluating the bitterness of hydrophobic compounds which respond to hTAS2R14 and their inhibitors.
Assuntos
Agentes Aversivos/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Paladar/efeitos dos fármacos , Agentes Aversivos/química , Humanos , Japão , Ligantes , Receptores Acoplados a Proteínas G/metabolismoRESUMO
The purpose of this study was to perform self-healing encapsulation of ONO-1301, a long-acting prostacyclin agonist, into poly(lactide-co-glycolide) (PLGA) microspheres using the oil-in-water (o/w) emulsion solvent evaporation method in order to try to limit the initial burst release of drug. Adequate self-healing of PLGA seemed to be achieved by stirring during the evaporation of solvent at 40°C close to the glass transition temperature (Tg) of the polymer (40.1°C). The plasticizers dimethylphthalate (DEP) or tributyl O-acetylcitrate (TBAC), at concentrations of 0.1-1.0%, to the internal oleogeneous phase in the o/w emulsion system was effective in restricting the initial burst release of the prepared microspheres. The combination of a self-healing at Tg of the polymer and the addition of 1% of each plasticizer was ultimately found to be the most effective in restricting the initial burst release. It is suggested that this is due to the synergistic effect of smooth surface morphology promoted by self-healing at Tg of the polymer and a decrease of the Tg of PLGA caused by the addition of plasticizers.
Assuntos
Epoprostenol/agonistas , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Piridinas/administração & dosagem , Varredura Diferencial de Calorimetria , Interações Hidrofóbicas e Hidrofílicas , Cinética , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solventes/química , TemperaturaRESUMO
The purpose of this study was to evaluate the taste-masking effects of chlorogenic acid (CGA) on bitter drugs using taste sensor measurements and surface plasmon resonance (SPR) analysis of CGA-drug interactions. Six different bitter drugs were used: amlodipine besylate (AMD), diphenhydramine hydrochloride (DPH), donepezil hydrochloride (DNP), rebamipide (RBM), diclofenac sodium (DCF) and etodolac (ETD). Taste sensor outputs were significantly inhibited by the addition of CGA to all drugs. The inhibition ratio of the taste sensor output decreased in the following order DPH>DNP>AMD≈DCF≈RBM≈ETD. The association rate constant (ka) for the interaction between drugs and CGA as evaluated by SPR measurement also decreased in the following order DPH>DNP>AMD>DCF≈ETD≈RBM. It was suggested that basic drugs (AMD, DNP, DPH) associate more easily with CGA than acidic drugs (DCF, RBM, ETD). The inhibition ratios (%) of the taste sensor output of bitter drugs caused by CGA and the association rate constants (ka) between the drugs and CGA were significantly correlated (rs=0.886, p<0.05, Spearman's correlation test). Our findings suggest that the taste-masking effects of CGA are due to its direct association with the drugs. CGA may therefore be a useful taste-masking agent for basic drugs.
Assuntos
Ácido Clorogênico/farmacologia , Interações Medicamentosas , Ressonância de Plasmônio de Superfície , Paladar/efeitos dos fármacos , Alanina/análogos & derivados , Anlodipino/farmacologia , Diclofenaco/farmacologia , Difenidramina/farmacologia , Donepezila , Etodolac/farmacologia , Indanos/farmacologia , Piperidinas/farmacologia , QuinolonasRESUMO
The purpose of the study was to evaluate suppression of the bitterness intensity of bitter basic drugs by chlorogenic acid (CGA) using the artificial taste sensor and human gustatory sensation testing and to investigate the mechanism underlying bitterness suppression using 1H-NMR. Diphenhydramine hydrocholoride (DPH) was the bitter basic drug used in the study. Quinic acid (QNA) and caffeic acid (CFA) together form CGA. Although all three acids suppressed the bitterness intensity of DPH in a dose-dependent manner as determined by the taste sensor and in gustatory sensation tests, CFA was less effective than either CGA or QNA. Data from 1H-NMR spectroscopic analysis of mixtures of the three acids with DPH suggest that the carboxyl group, which is present in both QNA and CGA but not CFA, interact with the amine group of DPH. This study showed that the bitterness intensity of DPH was suppressed by QNA and CGA through a direct electrostatic interaction with DPH as confirmed in 1H-NMR spectroscopic analysis. CGA and QNA may therefore be useful bitterness-masking agents for the basic drug DPH.
Assuntos
Ácido Clorogênico/farmacologia , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Adulto , Ácidos Cafeicos/farmacologia , Ácido Clorogênico/química , Difenidramina/química , Difenidramina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Ácido Quínico/farmacologia , Adulto JovemRESUMO
The purpose of the study was to evaluate the adsorption of filgrastim on infusion sets (comprising infusion bag, line and filter) and to compare the adsorption of the original filgrastim preparation with biosimilar preparations using HPLC. The inhibitory effect of polysorbate 80 on this adsorption was also evaluated. Filgrastim was mixed with isotonic sodium chloride solution or 5% (w/v) glucose solution in the infusion fluid. Filgrastim adsorption on infusion sets was observed with all preparations and with both types of infusion solution. The adsorption ratio was about 30% in all circumstances. Filgrastim adsorption on all parts of the infusion set (bag, line and filter) was dramatically decreased by the addition of polysorbate 80 solution at concentrations at or over its critical micelle concentration (CMC). The filgrastim adsorption ratio was highest at a solution pH of 5.65, which is the isoelectric point (pI) of filgrastim. This study showed that the degree of filgrastim adsorption on infusion sets is similar for original and biosimilar preparations, but that the addition of polysorbate 80 to the infusion solution at concentrations at or above its CMC is effective in preventing filgrastim adsorption. The addition of a total-vitamin preparation with a polysorbate 80 concentration over its CMC may be an effective way of preventing filgrastim adsorption on infusion sets.
Assuntos
Medicamentos Biossimilares/química , Filgrastim/química , Polissorbatos/farmacologia , Adsorção/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Polissorbatos/química , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
The purpose of this study was to determine which foods and/or drinks are capable of reducing the bitterness of topiramate when consumed together with the medicine. The inhibitory effects of foods/drinks (yoghurt and nine other foods/drinks) on the bitterness of topiramate (5 mg/mL) were evaluated with a taste sensor using a bitterness-responsive membrane (C00). The effect of topiramate on the taste characteristics of the foods/drinks themselves was also evaluated by taste sensor outputs. The viscosities of the foods/drinks and the influence of the lactic acid and orotic acid components of yoghurt, the most successful of the tested substances in taste masking, on the bitterness of topiramate were also measured. Yoghurt was predicted to be the most effective of the foods/drinks tested in reducing the acidic bitterness-responsive sensor output of topiramate. The outputs of the astringency sensor, sourness sensor, and saltiness sensor to yoghurt were not reduced by the addition of topiramate. The viscosity and lactic acid and orotic acid components of yoghurt seemed to be the keys in reducing the bitterness of topiramate. Yoghurt is predicted to be the food/drink most capable of reducing the bitterness of topiramate without losing the taste of the food/drink itself.
Assuntos
Bebidas , Alimentos , Frutose/análogos & derivados , Paladar/efeitos dos fármacos , Paladar/fisiologia , Frutose/análise , Frutose/farmacologia , Topiramato , ViscosidadeRESUMO
The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.
Assuntos
Famotidina/administração & dosagem , Famotidina/metabolismo , Paladar/efeitos dos fármacos , Paladar/fisiologia , Administração Oral , Adolescente , Adulto , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Solubilidade , Comprimidos , Adulto JovemRESUMO
The objective of this study was to evaluate an improved bitterness sensor which has been developed to allow the precise and sensitive prediction of the bitterness of acidic bitter pharmaceutical active ingredients, using as examples nine non-steroidal anti-inflammatory drugs (NSAIDs). The bitterness of the nine NSAIDs was measured using a multichannel taste-sensing system incorporating a bitterness sensor, C00, which has a membrane surface with high hydrophobicity, and was developed to allow an enhanced hydrophobic interaction with acidic bitter substances. The sourness intensities of the nine NSAIDs were also determined in gustatory sensation testing and by a taste sensor using a sourness-sensitive membrane, CA0. The 'Change in membrane Potential caused by Adsorption' (CPA) of sodium diclofenac and etodolac were also determined in the presence of increasing concentrations of tartaric acid using membrane C00. Multiple regression analysis performed on the data on bitterness intensity obtained using the taste sensor and in gustatory sensation testing showed that CPA values from C00 could be used to predict the bitterness of the NSAIDs. The derived equation was y = -0.0413 × CPA + 0.3164, where y represents the predicted bitterness intensity. There were concentration-dependent changes in the bitterness intensities of diclofenac sodium and etodolac without any change in their sourness intensities. For diclofenac sodium and etodolac, there was a good correlation between predicted and actual bitterness intensities in the presence of increasing concentrations of tartaric acid. The taste sensor may be useful for predicting the bitterness intensity of acidic bitter pharmaceutical active ingredients such as NSAIDs.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Técnicas Biossensoriais , Paladar/efeitos dos fármacos , Adulto , Algoritmos , Diclofenaco , Humanos , Concentração de Íons de Hidrogênio , Masculino , Adulto JovemRESUMO
Because stomatitis is a painful condition, gargling with lidocaine is often prescribed before meals. However, because lidocaine inhibits nerve conduction, lidocaine gargling may affect taste perception. Therefore, we studied the effects of lidocaine gargle on taste. We prepared samples of the 5 basic tastes at equivalent concentration levels in terms of the taste quotient. We conducted sensory tests to judge whether the samples could be tasted, and the threshold concentrations (50% taste rate) were estimated from the taste rates. The sensory test was repeated after the subjects gargled with lidocaine, and the efficacy ratio was calculated by comparing the threshold concentrations. Although no interaction was observed between the lidocaine gargle and the threshold concentration levels in the logistic regression analysis, significant differences were observed in the primary effects of each standard, such as the concentration levels, flavor, and bitterness. When the efficacy ratios based on the threshold values were calculated, increases in the thresholds for flavor and bitterness were observed. The results of this study suggested that gargling with lidocaine before a meal increases the thresholds for the appreciation of flavor and bitterness. This increase in the threshold values due to lidocaine was associated not with the pharmacological effect of the drug but with its strong bitterness.
Assuntos
Lidocaína/farmacologia , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Antissépticos BucaisRESUMO
The purpose of the study was to evaluate the compatibility of ozagrel sodium solution and calcium-containing transfusions using solubility product constants. We calculated the solubility product constant of mixtures of ozagrel sodium and calcium chloride and evaluated the compatibility of ozagrel sodium solution (both the original and generic products) with calcium chloride solution using a light obscuration particle counter. Various volumes of ozagrel solution were added to the calcium solutions to make final ozagrel concentrations of 0, 0.8, 1.6, 2.0, 2.4, 3.2 and 4.0 mmol/L. The solutions were gently agitated and stored at 25 and 40°C. The ozagrel concentration, calcium ion concentration and number of microparticles were measured. The solubility product constants obtained were 11.89×10(-9) mol(3)/L(3) (at 25°C) and 7.82×10(-9) mol(3)/L(3) (40°C). The number of insoluble microparticles was significantly increased when the ionic product was larger than the solubility product constant. In all ozagrel sodium products, the number of insoluble microparticles was within the allowable range according to the Japanese Pharmacopoeia. These results suggest that mixing ozagrel sodium with calcium-containing products is safe and without appreciable risk of incompatibility under clinical conditions.