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A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery
A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

Fused Deposition Modelling (a.k.a. FDM-3D printing) has been previously employed in the development of personalized medicines with unique properties and release behavior. In the present work, a bilayer dosage form containing two anti-diabetic drugs with different daily dosage regimens; i.e. metformin and glimepiride, was manufactured via FDM 3D printing, studied using a variety of techniques and characterized in vitro. Metformin and glimepiride were embedded in Eudragit® RL sustained release layer and polyvinyl alcohol (PVA) layer respectively. Incorporation of more than one API's into the formulation is desirable, as it increases patient compliance and reduces cost of treatment, especially when distinct dosages of API's can be adjusted individually in situ, in order to meet each patient's specific needs, a capability provided by 3D printing. A number of different preparation methods, which involved different plasticizers and extruders, were tested on manufacturing Eudragit® RL drug-loaded filaments for printing the sustained release layer. The properties of the produced filaments were assessed by means of mechanical and physicochemical characterization techniques and the filaments with the optimum properties were used for printing. Microfocus computed tomography (μCT) imaging-based actual/nominal comparison analysis showed a printing accuracy ranging between −100, +200 μm, while X-ray (XRD) diffractograms revealed the incorporation of the (initially crystalline) API's as amorphous dispersions into polymer matrices. Dissolution tests showed sufficient drug release for both drugs in desired time frames (75 min for glimepiride and 480 min for metformin). The results from the current study emphasize the potentiality of 3D printing technology for tailor-made solid dosage forms for combined pharmacotherapy, even at the cases when API's with different desirable release profiles are employed.

3D printing, Bilayer dosage form, Fused deposition modelling, Glimepiride, Mechanical properties, Metformin, Micro-computer tomography
0928-0987
40-52
Gioumouxouzis, Christos I.
6bbfb151-763a-48dc-8d1f-9cabd27c8d11
Baklavaridis, Apostolos
33e1c7fb-5a22-4177-a647-b335b5a28d6d
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Markopoulou, Catherine K.
285881c8-7b68-48ce-a3d6-af5076150cfd
Bouropoulos, Nikolaos
fadadea1-2aa2-4cd9-a7e5-33ba790cd45f
Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Fatouros, Dimitrios G.
4a716c96-a8ba-4fbf-b3db-3b2a3a2794c4
Gioumouxouzis, Christos I.
6bbfb151-763a-48dc-8d1f-9cabd27c8d11
Baklavaridis, Apostolos
33e1c7fb-5a22-4177-a647-b335b5a28d6d
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Markopoulou, Catherine K.
285881c8-7b68-48ce-a3d6-af5076150cfd
Bouropoulos, Nikolaos
fadadea1-2aa2-4cd9-a7e5-33ba790cd45f
Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Fatouros, Dimitrios G.
4a716c96-a8ba-4fbf-b3db-3b2a3a2794c4

Gioumouxouzis, Christos I., Baklavaridis, Apostolos, Katsamenis, Orestis L., Markopoulou, Catherine K., Bouropoulos, Nikolaos, Tzetzis, Dimitrios and Fatouros, Dimitrios G. (2018) A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery. European Journal of Pharmaceutical Sciences, 120, 40-52. (doi:10.1016/j.ejps.2018.04.020).

Record type: Article

Abstract

Fused Deposition Modelling (a.k.a. FDM-3D printing) has been previously employed in the development of personalized medicines with unique properties and release behavior. In the present work, a bilayer dosage form containing two anti-diabetic drugs with different daily dosage regimens; i.e. metformin and glimepiride, was manufactured via FDM 3D printing, studied using a variety of techniques and characterized in vitro. Metformin and glimepiride were embedded in Eudragit® RL sustained release layer and polyvinyl alcohol (PVA) layer respectively. Incorporation of more than one API's into the formulation is desirable, as it increases patient compliance and reduces cost of treatment, especially when distinct dosages of API's can be adjusted individually in situ, in order to meet each patient's specific needs, a capability provided by 3D printing. A number of different preparation methods, which involved different plasticizers and extruders, were tested on manufacturing Eudragit® RL drug-loaded filaments for printing the sustained release layer. The properties of the produced filaments were assessed by means of mechanical and physicochemical characterization techniques and the filaments with the optimum properties were used for printing. Microfocus computed tomography (μCT) imaging-based actual/nominal comparison analysis showed a printing accuracy ranging between −100, +200 μm, while X-ray (XRD) diffractograms revealed the incorporation of the (initially crystalline) API's as amorphous dispersions into polymer matrices. Dissolution tests showed sufficient drug release for both drugs in desired time frames (75 min for glimepiride and 480 min for metformin). The results from the current study emphasize the potentiality of 3D printing technology for tailor-made solid dosage forms for combined pharmacotherapy, even at the cases when API's with different desirable release profiles are employed.

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More information

Accepted/In Press date: 16 April 2018
e-pub ahead of print date: 17 April 2018
Published date: 30 July 2018
Keywords: 3D printing, Bilayer dosage form, Fused deposition modelling, Glimepiride, Mechanical properties, Metformin, Micro-computer tomography

Identifiers

Local EPrints ID: 422489
URI: http://eprints.soton.ac.uk/id/eprint/422489
ISSN: 0928-0987
PURE UUID: 0084aa6f-ac24-450a-8687-0b30b489eb9d
ORCID for Orestis L. Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147

Catalogue record

Date deposited: 24 Jul 2018 16:31
Last modified: 17 Dec 2019 05:26

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Contributors

Author: Christos I. Gioumouxouzis
Author: Apostolos Baklavaridis
Author: Catherine K. Markopoulou
Author: Nikolaos Bouropoulos
Author: Dimitrios Tzetzis
Author: Dimitrios G. Fatouros

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