Model-Informed Strategies for Methocarbamol Multiparticulate Regimen Development

Model-Informed Strategies for Methocarbamol Multiparticulate Regimen Development: Linking Mechanistic Modelling to Formulation Design Space

Methocarbamol, a centrally acting skeletal muscle relaxant, is a BCS Class I compound characterised by rapid absorption and a short half-life, necessitating frequent dosing (three times daily, TID) to maintain therapeutic exposure. Despite its favourable permeability and solubility, the associated TID dosing burden presents challenges for patient adherence and optimal treatment. 

To address this, a Physiologically Based Pharmacokinetic (PBPK) model was developed using GastroPlus® and subsequently verified using several published clinical studies with immediate-release (IR) formulations. This enabled a reliable characterization of methocarbamol ADME properties and established a quantitative framework to support a rational formulation development. 

The validated model was subsequently used to define the target product profile (TPP) for the 1500 mg TID immediate release (IR) reference regimen (total dose of 4500 mg). 

This research work leverages model-informed drug development to design a simplified twice-daily (BID) multiparticulate formulation combining immediate- and modified-release (IR+MR) components to match the reference exposure. It also establishes a robust formulation design space that incorporates uncertainties related to lower gastrointestinal (GI) absorption and the release kinetics.