Co‐extrusion as a processing technique to manufacture a dual sustained release fixed‐dose combination product. (11th January 2016)

• Record Type: Journal Article
• Authors: Vynckier, An‐Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris
• Other Names: Jones David S guestEditor.; Dressman Jennifer B guestEditor.
• Is Part Of: Journal of pharmacy and pharmacology. Volume 68:Number 5(2016:May)
• Page Start: 721
• Page End: 727
• Publication Date: 2016-01-11
• Subjects: continuous production -- fixed‐dose combination product -- hot‐melt co‐extrusion -- sustained release; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12521
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: This study aimed to design a fixed‐dose combination dosage form which provides a sustained release profile for both the freely water‐soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Methods: Hot‐melt co‐extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed‐dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. Key findings: It was clear that co‐extrusion was perfectly suited to produce a fixed‐dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA ® 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl‐loaded CAPA ® 6506 core of the co‐extrudate. To obtain a complete gliclazide release over 24‐h solubilization in Kollidon ® VA, added as a second polymer to the CAPA ® 6506 in the coat, was needed. Conclusions: Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co‐extrusion.