Comparative in vitro Dissolution and in vivo Bioavailability of Diflunisal/Naproxen Fixed-Dose Combination Tablets and Concomitant Administration of Diflunisal and Naproxen in Healthy Adult Subjects

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively. In vitro dissolution and in vivo absorption of the four drugs in the jellies were compared with other conventional formulations, a syrup and two types of immediate-release (IR) tablets with different hardness, Tablet-S (15 kPa) and Tablet-H (20 kPa). All the formulations exhibited more than 80% dissolution rate within 2 h even though the syrup, Jelly-S, and Tablet-S showed higher 30-min dissolution compared to Jelly-H and Tablet-H. The dissolution rates from the jellies decreased with increasing pH, which resulted in the slowest dissolution in pH 6.8 compared to the syrup and IR tablets. When administered orally to beagle dogs, all five formulations were determined not to be bioequivalent. However, Jelly-S and Jelly-H showed 0.82–1.05 of the geometric mean ratios (GMRs) of AUC0-t for all four drugs compared to the syrup suggesting comparable absorption. In two IR tablets, GMRs of AUC0-t were in a range of 0.55–0.95 indicating a tendency of lower absorption than the syrup and jellies. In conclusion, jelly can be a patient-centered formulation with comparable bioavailability to syrup.

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Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

Drug Design Development and Therapy ◽

10.2147/dddt.s148534 ◽

2017 ◽

Vol Volume 11 ◽

pp. 3543-3550 ◽

Cited By ~ 5

Author(s):

Minkyung Oh ◽

Sung-Eun Park ◽

Jong-Lyul Ghim ◽

Young-Kyung Choi ◽

Eon-Jeong Shim ◽

...

Keyword(s):

Healthy Adult ◽

Concomitant Administration ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Dose Combination ◽

Adult Volunteers

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RAPID AND SIMPLE DETERMINATION OF IBUPROFEN AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i3.40975 ◽

2021 ◽

pp. 242-246

Author(s):

JOSE RAUL MEDINA-LOPEZ ◽

JOAQUIN ALEXANDRO SOTO-JUHA ◽

JUAN MANUEL CONTRERAS-JIMÉNEZ

Keyword(s):

Fixed Dose Combination ◽

In Vitro Dissolution ◽

Fixed Dose ◽

Published Data ◽

Weibull Function ◽

Zero Crossing ◽

Derivative Method ◽

Dose Combination

Objective: To develop a UV-derivative spectrophotometric method with zero-crossing determinations for the simultaneous quantification of ibuprofen (IBU) and caffeine (CAF) in fixed-dose combination formulations (soft gelatin capsules). The proposed method was validated, and it was applied to determine the in vitro dissolution performance of IBU and CAF from a commercial formulation. Methods: The method is based on the use of the second-derivatives of the zero-order spectra and measurement at zero-crossing wavelengths. Linearity, accuracy, precision, stability, and influence of the filter were evaluated. Dissolution profiles of IBU and CAF were obtained with the USP Apparatus 2 at 100 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4 as dissolution medium. Dissolution samples were treated with the proposed UV-derivative method and results were compared with data previously published. Results: The zero-crossing points for the determination of IBU and CAF were found at 235.6 nm and 218.8 nm, respectively. The method was linear in the range of 7.5-15 µg/ml for IBU and 5-25 µg/ml for CAF (R2>0.999, *P<0.05). The precision and accuracy of the method were within acceptable criteria (CV<0.99% and recovery 97.97% for IBU and CV<1.76% and recovery 99.05% for CAF). Fiberglass filters were the best option to filter samples and stability of all drugs was adequate when solutions were stored at 25 °C during 24 h. Dissolution of IBU and CAF at 60 min was 99-100% with dissolution profiles of sigmoidal S-shape. Weibull function and Logistic were the best-fit models that describe the in vitro dissolution performance of both drugs. Conclusion: The proposed UV-derivative method allows the simultaneous determination of IBU and CAF in fixed-dose combination formulations. The method generates reliable information that can be compared with published data. The proposed UV-derivative method is rapid and simple and can be easily adopted for routine analysis of IBU and CAF.

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