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Published on: December 1, 2023
Co-extrusion as manufacturing technique for fixed-dose combination mini-matrices
L Dierickx1, L Saerens, A Almeida
1Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Summary
This study developed a novel multilayer mini-tablet using co-extrusion for controlled drug delivery. The innovative dosage form successfully combined sustained release metoprolol tartrate and immediate release hydrochlorothiazide with good in vitro and in vivo performance.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Materials Science
Background:
- Developing advanced dosage forms is crucial for improving patient compliance and therapeutic efficacy.
- Multilayer drug delivery systems offer potential for combining drugs with different release profiles.
- Co-extrusion is a promising manufacturing technique for creating complex pharmaceutical structures.
Purpose of the Study:
- To develop a multilayer (core/coat) dosage form using co-extrusion for distinct drug release profiles.
- To incorporate sustained release metoprolol tartrate (MPT) in the core and immediate release hydrochlorothiazide (HCT) in the coat.
- To evaluate the processability, drug release, and in vivo performance of the developed formulation.
Main Methods:
- Screening of thermoplastic polymers for co-extrusion suitability.
- Hot-melt extrusion and co-extrusion of polycaprolactone (core) and polyethylene oxide (coat) with MPT and HCT.
- In vitro drug release studies for HCT and MPT.
- Characterization using Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Raman spectroscopy.
- In vivo study comparing the experimental formulation with a reference tablet.
Main Results:
- Successful co-extrusion of a multilayer mini-tablet (3 mm core diameter, 0.5 mm coat thickness) with good layer adhesion.
- Complete release of HCT within 30 minutes from the coat.
- Sustained release of MPT over 24 hours from the core (55% at 4h, 70% at 8h, 85% at 12h, 100% at 24h).
- MPT remained crystalline, while HCT was dissolved in the polyethylene oxide matrix.
- No significant difference in in vivo performance compared to the reference formulation.
Conclusions:
- Co-extrusion is an effective method for producing multilayer fixed-dose combination mini-tablets.
- The developed polycaprolactone/polyethylene oxide formulation provides both immediate and sustained drug release.
- The mini-tablets demonstrate good in vitro and in vivo performance, offering a viable alternative to conventional tablets.
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