Dataset Information

In Vivo Evaluation of Thiamine Hydrochloride with Gastro-Retentive Drug Delivery in Healthy Human Volunteers Using Gamma Scintigraphy.

ABSTRACT: A floating tablet system containing thiamine hydrochloride, a model drug with a narrow absorption window, was evaluated. The tablet was found to have a floating lag time of less than 30 s with a sustained drug release over 12 h during in vitro dissolution studies. The gastro-retentive property of the tablet in relation to the bioavailability of thiamine was determined in healthy human volunteers using gamma scintigraphy under fasted and fed conditions. The gastro-retentive time of the floating tablet could be prolonged up to 10 h under the fed state, compared to about 1.8 h in the fasted state. The prolonged gastric retention under the fed state resulted in a 2.8-fold increase in oral bioavailability of thiamine compared to that of the fasted state. There was also a 1.4-fold increase in thiamine absorption compared to that of a conventional immediate release tablet in the fed state. In the fasted state, the extent of thiamine absorption from the floating tablet was only about 70% of that absorbed from the immediate release tablet. Thus, to achieve a better performance, such floating tablet systems should be administered under a fed condition, to prolong the gastric retention time.

SUBMITTER: Kam LY

PROVIDER: S-EPMC9960539 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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In Vivo Evaluation of Thiamine Hydrochloride with Gastro-Retentive Drug Delivery in Healthy Human Volunteers Using Gamma Scintigraphy.

Kam Li-Ying LY Wong Jia-Woei JW Yuen Kah-Hay KH

Pharmaceutics 20230217 2

A floating tablet system containing thiamine hydrochloride, a model drug with a narrow absorption window, was evaluated. The tablet was found to have a floating lag time of less than 30 s with a sustained drug release over 12 h during in vitro dissolution studies. The gastro-retentive property of the tablet in relation to the bioavailability of thiamine was determined in healthy human volunteers using gamma scintigraphy under fasted and fed conditions. The gastro-retentive time of the floating t ...[more]

PMID: 36840013

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Project description:IntroductionSmall-field-of-view (SFOV) gamma cameras can offer higher sensitivities than conventional gamma cameras. However, there are currently no reports on the efficacy and safety of thyroid scintigraphy using SFOV gamma cameras in veterinary medicine. Therefore, we aimed to evaluate the efficacy and radiation safety of an SFOV gamma camera for feline thyroid scintigraphy.Materials and methodsThree veterinary staff members (operator, staff 1, and staff 2) performed thyroid scintigraphy on 10 healthy cats in this study. The operator administered either 2 or 4 mCi of technetium-99m pertechnetate (99mTcO- 4) through the cephalic vein. At 20, 40, and 60 min after injection, thyroid images were obtained using a SFOV gamma camera under various acquisition conditions (100,000, 150,000, and 200,000 counts and 30 and 60 s). Thyroid scintigraphy images were analyzed by calculating the thyroid-to-salivary ratios (TSR) and thyroid-to-background ratios (TBR). Surface and ambient radiation were measured hourly from immediately after injection to 6 h. The cumulative occupational radiation doses were measured during the procedure.ResultsThe TSR and TBR median values aligned with the previously reported normal range obtained using a large-field-of-view gamma camera. There were no notable differences in TSR and TBR between the two doses of 99mTcO- 4, nor across acquisition conditions and timelines. The 4-mCi group consistently emitted more ambient (p < 0.05) and surface (p < 0.05) radiation than did the 2-mCi group. Staff 1 consistently received higher cumulative radiation doses than did staff 2 and the operator (p < 0.05).ConclusionThe SFOV gamma camera demonstrated adequate image quality for thyroid scintigraphy in healthy cats even with relatively low doses and short acquisition conditions. Radiation exposure during the procedure posed minimal safety concerns. Therefore, the SFOV gamma camera could be a valuable tool for evaluating thyroid glands in cats.

Project description:PurposeThis study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug.Materials and methodsA randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC0-t, AUC0-∞), the peak plasma concentration (Cmax), the time to achieve Cmax (Tmax), and the elimination half-life (t1/2). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs).ResultsThe values of t1/2 and Tmax for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of Cmax, AUC0-t, and AUC0-∞ between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events.ConclusionThis study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.

Project description:Thiamine (vitamin B1) is an essential micronutrient in the human diet, found both naturally and as a fortification ingredient in many foods and supplements. However, it is susceptible to degradation due to heat, light, alkaline pH, and sulfites, among effects from other food matrix components, and its degradation has both nutritional and sensory implications as in foods. Thiamine storage stability in solution was monitored over time to determine the effect of solution pH and thiamine concentration on reaction kinetics of degradation without the use of buffers, which are known to affect thiamine stability independent of pH. The study directly compared thiamine stability in solutions prepared with different pHs (3 or 6), concentrations (1 or 20 mg/mL), and counterion in solution (NO3-, Cl-, or both), including both commercially available salt forms of thiamine (thiamine mononitrate and thiamine chloride hydrochloride). Solutions were stored at 25, 40, 60, and 80 °C for up to one year, and degradation was quantified by high-performance liquid chromatography (HPLC) over time, which was then used to calculate degradation kinetics. Thiamine was significantly more stable in pH 3 than in pH 6 solutions. In pH 6 solutions, stability was dependent on initial thiamine concentration, with the 20 mg/mL thiamine salt solutions having an increased reaction rate constant (kobs) compared to the 1 mg/mL solutions. In pH 3 solutions, kobs was not dependent on initial concentration, attributed to differences in degradation pathway dependent on pH. Activation energies of degradation (Ea) were higher in pH 3 solutions (21-27 kcal/mol) than in pH 6 solutions (18-21 kcal/mol), indicating a difference in stability and degradation pathway due to pH. The fundamental reaction kinetics of thiamine reported in this study provide a basis for understanding thiamine stability and therefore improving thiamine delivery in many foods containing both natural and fortified thiamine.

Dataset Information

In Vivo Evaluation of Thiamine Hydrochloride with Gastro-Retentive Drug Delivery in Healthy Human Volunteers Using Gamma Scintigraphy.

Publications

In Vivo Evaluation of Thiamine Hydrochloride with Gastro-Retentive Drug Delivery in Healthy Human Volunteers Using Gamma Scintigraphy.

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