Enabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs
Artikel i vetenskaplig tidskrift, 2021

Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy.

Oral drug release

Amorphous solid dispersions

Melt extrusion

Flexible combinations

Polypharmacy

Mass customization

Författare

Rydvikha Govender

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Anette Larsson Group

AstraZeneca AB

Susanna Abrahmsén-Alami

AstraZeneca AB

Staffan Folestad

AstraZeneca AB

Martina Olsson

Chalmers, Fysik, Materialfysik

Anette Larsson

Chalmers, Kemi och kemiteknik, Tillämpad kemi, Anette Larsson Group

International Journal of Pharmaceutics

0378-5173 (ISSN)

Vol. 602 120625

Ämneskategorier

Design

Farmaceutisk vetenskap

Interaktionsteknik

DOI

10.1016/j.ijpharm.2021.120625

PubMed

33892062

Mer information

Senast uppdaterat

2021-05-12