Effects of Postprandial Factors and Second Meal Intake Time on Bioequivalence Investigation of Tadalafil-Loaded Orodispersible Films in Human Volunteers

Author:

Park Su-Jun12,Gil Myung-Chul3ORCID,Lee Bong-Sang3,Jung Minji4ORCID,Lee Beom-Jin15ORCID

Affiliation:

1. Department of Pharmacy, College of Pharmacy, Ajou University, Suwon-si 16499, Republic of Korea

2. CTCBIO Inc., Hwaseong-si 18576, Republic of Korea

3. PLUTO Inc., Seongnam-si 13453, Republic of Korea

4. Department of Urology, School of Medicine, Stanford University, Stanford, CA 94305, USA

5. Institute of Pharmaceutical Science and Technology, Ajou University, Suwon-si 16499, Republic of Korea

Abstract

Tadalafil (TD) has poor water solubility but is well absorbed without affecting food intake when administered orally. Owing to patient adherence and therapeutic characteristics, a TD-loaded orodispersible film (TDF) is preferable. However, the mechanistic role of dietary status on the clinical pharmacokinetic analysis of TDF in human volunteers should be investigated because the gastrointestinal environment varies periodically according to meal intervals, although commercial 20 mg TD-loaded tablets (TD-TAB, Cialis® tablet) may be taken with or without food. TDF was prepared by dispersing TD in an aqueous solution and polyethylene glycol 400 to ensure good dispersibility of the TD particles. In the fasting state, each T/R of Cmax and AUC between TD-TAB and TDF showed bioequivalence with 0.936–1.105 and 1.012–1.153, respectively, and dissolution rates in 1000 mL water containing 0.5% SLS were equivalent. In contrast, TDF was not bioequivalent to TD-TAB under the fed conditions by the Cmax T/R of 0.610–0.798. The increased dissolution rate of TDF via the micronization of drug particles and the reduced viscosity of the second meal content did not significantly affect the bioequivalence. Interestingly, an increase in second meal intake time from 4 h to 6 h resulted in the bioequivalence by the Cmax T/R of 0.851–0.998 of TD-TAB and TDF. The predictive diffusion direction model for physical digestion of TD-TAB and TDF in the stomach after the first and second meal intake was successfully simulated using computational fluid dynamics modeling, accounting for the delayed drug diffusion of TDF caused by prolonged digestion of stomach contents under postprandial conditions.

Funder

Korea Health Industry Development Institute

Publisher

MDPI AG

Reference68 articles.

1. Nanosuspension for Oral Delivery of Tadalafil: Pharmacodynamic and Pharmacokinetic Studies;Patel;J. Drug Deliv. Sci. Technol.,2021

2. Anderson, N.R., Hartauer, K.J., Kral, M.A., and Stephenson, G.A. (2004). Beta-Carboline Drug Products. (6,821,975 B1), U.S. Patent.

3. Tadalafil Pharmacokinetics in Healthy Subjects;Forgue;Br. J. Clin. Pharmacol.,2006

4. Dose-Normalised Pharmacokinetics of Tadalafil Administered as a Single Dose to Healthy Volunteers;Patterson;Eur. Urol. Suppl. Off. J. Eur. Assoc. Urol.,2002

5. A Multicenter, Randomized, Double-Blind, Crossover Study to Evaluate Patient Preference between Tadalafil and Sildenafil;Rajfer;Eur. Urol.,2004

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