In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers

Abstract

Following a single oral drug administration, Ritalin LA demonstrated a two-peak plasma concentration-time profile, similar to that of the IR formulation given 4 h apart, but with less fluctuation in the plasma concentration-time profile. The in vivo biphasic absorption of MPH appeared to be well correlated with the bimodal dissolution characteristics of this new Ritalin LA formulation, and some changes in the dissolution profiles for the DR beads appeared not to affect the overall bioavailability of MPH in humans.

A General Framework for Assessing In vitro/In vivo Correlation as a Tool for Maximizing the Benefit‐Risk Ratio of a Treatment Using a Convolution‐Based Modeling Approach

“…concluded that the three formulations were bioequivalent despite a different shape of the PK time courses. It should be noted that the criteria used by Wang et al . to assess the bioequivalence of MPH formulations (Ritalin LA) are not the same as the current recommendations of the FDA .…”

“…The original study enrolled 17 participants in a fourtreatment, four-period, single-dose, randomized crossover design study, but only 16 subjects were retained for the final PK analysis. 11 The subjects received four treatments, after at least a 10-hour fast, 3 Ritalin LA capsule formulations (40 mg) and Ritalin IR tablets (two 20 mg given 4 hours apart) as the reference. The three Ritalin LA formulations were selected to provide slow-release, medium-release, and fast-release in vitro dissolution rates, respectively.…”

“…Ritalin LA data extracted from the literature were used to implement an IVIVC. 11 The PK/PD model previously developed to establish the exposure-response of MPH was used to estimate the changes in Swanson, Kotkin, Agler, M-Flynn, and Pelham scale (SKAMP) clinical scores associated with a single dose of 40 mg of Ritalin LA. 12 Finally, the optimization algorithm was applied to identify the dose and the in vivo/in Figure 1 General framework for maximizing the benefit-risk ratio of a treatment.…”

In Vitro–In Vivo Correlations

“…12,89,90,91,92 In addition, an IVIVC should not be developed using plasma concentrations of racemate when there are stereoselective dissolution or absorption differences between the two enantiomers. 93 More importantly, the dissolution process should be the rate-limiting step in the absorption process, as discussed previously. In most cases, IVIVC models are being established using average in vivo response, thus ignoring the inter-and intra-subject variability.…”

The EEG Consistency Index as a Psycho-Physiological Marker of ADHD and Methylphenidate Response: Replication of Results

“…Optimal dosage included achieving a balance of maximizing effectiveness for symptom relief while minimizing negative side effects. For the first EEG acquisition, all shortacting stimulant medications were discontinued for at least 24 hours prior to the assessment, which is considered to be an adequate amount of time for the stimulant to be out of the participants' systems, and therefore not impact the EEG data (Wang et al, 2003). No participants were currently taking long-acting stimulant medications.…”