Journal of Bioequivalence & Bioavailability

Steady-state bioavailability of extended-release methylphenidate capsules vs. immediate-release methylphenidate tablets in healthy adult volunteers

7^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit

August 29-31, 2016 Atlanta, USA

Akwete Lex Adjei

Rhodes Pharmaceuticals L.P., USA

Keynote: J Bioequiv Availab

Abstract:

A novel formulation of extended-release (ER) methylphenidate hydrochloride that utilizes multiple layers of coatings on beads for encapsulation into hard gelatin capsule shells (Aptensio®, MPH-MLR) was evaluated to determine the relative bioavailability vs. immediate-release methylphenidate tablets (IR, Ritalin®) as single and multiple doses in the fed state. A single-center, 4-day, multiple-dose, randomized, open-label, 2-period crossover study design assessed the relative bioavailability of MPH-MLR 80 mg once daily versus Ritalin® IR 25 mg 3 times daily (TID) in 26 healthy adults. Serial blood samples were collected at pre-specified time points over the 4-day dosing period for determination of methylphenidate concentration and pharmacokinetic analyses. Relative bioavailability of MPH-MLR versus Ritalin® (75 mg total daily dose normalized to a single dose of MPH-MLR) as a single dose under fed conditions, and at steady state under fed conditions, was determined based on AUC0-t, AUC0-inf and Cmax of methylphenidate. MPH-MLR administration produced a rapid initial peak, a moderate decline until ~5 hours postdose, and a gradual increase until ~7 hours postdose. Cmax was lower for MPHMLR 80 mg than methylphenidate IR 25 mg on Day 1. Exposure was similar with 90% CI limits for the geometric mean ratios of log-transformed AUC0-t that were within the 80%-125% equivalence range. Day 4 partial AUC0-4 (74.49±15.23 hr.ng/mL) for MPH-MLR exceeded Ritalin IR 25 mg 3 times daily (66.01±17.41 hr.ng/mL), and therefore was not bioequivalent. MPH-MLR capsules administered once daily and methylphenidate IR administered TID provided comparable maximum methylphenidate concentrations and systemic exposure in the fed state.

Biography :

Akwete Lex Adjei has completed his PhD from the University of Texas, Austin and his Postgraduate work on complexation of xanthine drugs in non-ideal solvent systems. He has held positions at several pharmaceutical companies and he is currently an Executive Director of R&D at Rhodes Pharmaceuticals, L.P. He has been the author/co-author of 38 published peer-reviewed articles and 15 books or book chapters and has almost 50 patents for his work in this area.

Email: Akwete.Adjei@pharma.com