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In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers.
Biopharm Drug Dispos. 2004 Mar; 25(2):91-8.BD

Abstract

PURPOSE

The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L-threo-methylphenidate (MPH) from a novel bimodal release formulation (Ritalin LA capsule) compared with an immediate-release formulation (Ritalin IR tablet) in healthy volunteers.

METHODS

The bimodal release formulation contains 50% of the dose in the immediate-release (IR) beads and 50% in polymethacrylate-coated, delayed-release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow-, medium and fast-release formulations) were prepared, and tested together with the immediate-release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration-time profile. The in vivo absorption-time profile was also examined by deconvolution.

RESULTS

All three Ritalin LA formulations demonstrated similar bimodal plasma concentration-time profiles with two peak concentrations observed at approximately 2 and approximately 6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to approximately 2 h, and a somewhat slower second absorption between approximately 3-6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC.

CONCLUSIONS

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.

Authors+Show Affiliations

Clinical Pharmacology, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. yanfeng.wang@pharma.novartis.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article

Language

eng

PubMed ID

14872557

Citation

Wang, Yanfeng, et al. "In Vitro Dissolution and in Vivo Oral Absorption of Methylphenidate From a Bimodal Release Formulation in Healthy Volunteers." Biopharmaceutics & Drug Disposition, vol. 25, no. 2, 2004, pp. 91-8.
Wang Y, Lee L, Somma R, et al. In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers. Biopharm Drug Dispos. 2004;25(2):91-8.
Wang, Y., Lee, L., Somma, R., Thompson, G., Bakhtiar, R., Lee, J., Rekhi, G. S., Lau, H., Sedek, G., & Hossain, M. (2004). In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers. Biopharmaceutics & Drug Disposition, 25(2), 91-8.
Wang Y, et al. In Vitro Dissolution and in Vivo Oral Absorption of Methylphenidate From a Bimodal Release Formulation in Healthy Volunteers. Biopharm Drug Dispos. 2004;25(2):91-8. PubMed PMID: 14872557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers. AU - Wang,Yanfeng, AU - Lee,Lucy, AU - Somma,Russell, AU - Thompson,Glenn, AU - Bakhtiar,Ray, AU - Lee,James, AU - Rekhi,Gurvinder Singh, AU - Lau,Henry, AU - Sedek,Greg, AU - Hossain,Mohammad, PY - 2004/2/12/pubmed PY - 2004/12/16/medline PY - 2004/2/12/entrez SP - 91 EP - 8 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 25 IS - 2 N2 - PURPOSE: The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L-threo-methylphenidate (MPH) from a novel bimodal release formulation (Ritalin LA capsule) compared with an immediate-release formulation (Ritalin IR tablet) in healthy volunteers. METHODS: The bimodal release formulation contains 50% of the dose in the immediate-release (IR) beads and 50% in polymethacrylate-coated, delayed-release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow-, medium and fast-release formulations) were prepared, and tested together with the immediate-release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration-time profile. The in vivo absorption-time profile was also examined by deconvolution. RESULTS: All three Ritalin LA formulations demonstrated similar bimodal plasma concentration-time profiles with two peak concentrations observed at approximately 2 and approximately 6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to approximately 2 h, and a somewhat slower second absorption between approximately 3-6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC. CONCLUSIONS: 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. SN - 0142-2782 UR - https://www.unboundmedicine.com/medline/citation/14872557/In_vitro_dissolution_and_in_vivo_oral_absorption_of_methylphenidate_from_a_bimodal_release_formulation_in_healthy_volunteers_ L2 - https://doi.org/10.1002/bdd.390 DB - PRIME DP - Unbound Medicine ER -