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Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients

Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients
Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients

In pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug. By removing parts of the shell (upper surface, linear lateral segments) were created dosage forms that modify their shape at specific time frames under the effect of the gradually induced osmotic pressure. Hot-Melt Extrusion (HME) was employed to fabricate two different 3DP feeding filaments, for the creation of either the shell or the osmotic core (dual-extrusion printing). Printed formulations and filaments were characterized by means of (TGA, XRD, DSC) and inspected using microscopy (optical and electron). The mechanical properties of the filaments were assessed by means of micro- and macro mechanical testing, whereas micro-Computed Tomography (μCT) was employed to investigate the volumetric changes occurring during the hydration process. XRD indicated the amorphization of DIL inside HME filaments and printed dosage forms, whereas the incorporated NaCl (osmogen) retained its crystallinity. Mechanical properties' testing confirmed the printability of produced filaments. Dissolution tests revealed that all formulations exhibited sustained release differing at the initiation time of the API dissolution (0, 120 and 360 min for the three different formulations). Finally, μCT uncovered the key structural changes assonated with distinct phases of the release profile. The above results demonstrate the successful utilization of an FDM 3D printer in order to create osmotic 3D printed formulations exhibiting sustained and/or delayed release, that can be easily personalized containing API doses corresponding to each patient's specific needs.

3D printing, Additive manufacturing, Cellulose acetate, Controlled release, Osmotic system, Personalized medicine, micro-Computed tomography
0928-0987
1-13
Gioumouxouzis, Christos I
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Tzimtzimis, Emmanouil
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Katsamenis, Orestis L
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Dourou, Anthi
0e287dbf-858d-4010-ac2f-7c2f7f236a0e
Markopoulou, Catherine
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
Tzimtzimis, Emmanouil
2d6821e9-9e4c-45df-98cd-8b1da210fb94
Katsamenis, Orestis L
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Dourou, Anthi
0e287dbf-858d-4010-ac2f-7c2f7f236a0e
Markopoulou, Catherine
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, Tzimtzimis, Emmanouil, Katsamenis, Orestis L, Dourou, Anthi, Markopoulou, Catherine, Bouropoulos, Nikolaos, Tzetzis, Dimitrios and Fatouros, Dimitrios G (2020) Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients. European Journal of Pharmaceutical Sciences, 143, 1-13, [105176]. (doi:10.1016/j.ejps.2019.105176).

Record type: Article

Abstract

In pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug. By removing parts of the shell (upper surface, linear lateral segments) were created dosage forms that modify their shape at specific time frames under the effect of the gradually induced osmotic pressure. Hot-Melt Extrusion (HME) was employed to fabricate two different 3DP feeding filaments, for the creation of either the shell or the osmotic core (dual-extrusion printing). Printed formulations and filaments were characterized by means of (TGA, XRD, DSC) and inspected using microscopy (optical and electron). The mechanical properties of the filaments were assessed by means of micro- and macro mechanical testing, whereas micro-Computed Tomography (μCT) was employed to investigate the volumetric changes occurring during the hydration process. XRD indicated the amorphization of DIL inside HME filaments and printed dosage forms, whereas the incorporated NaCl (osmogen) retained its crystallinity. Mechanical properties' testing confirmed the printability of produced filaments. Dissolution tests revealed that all formulations exhibited sustained release differing at the initiation time of the API dissolution (0, 120 and 360 min for the three different formulations). Finally, μCT uncovered the key structural changes assonated with distinct phases of the release profile. The above results demonstrate the successful utilization of an FDM 3D printer in order to create osmotic 3D printed formulations exhibiting sustained and/or delayed release, that can be easily personalized containing API doses corresponding to each patient's specific needs.

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2019_EurJPharmSci._[Gioumouxouzis_et_al]-pre-proof - Accepted Manuscript
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More information

Accepted/In Press date: 3 December 2019
e-pub ahead of print date: 4 December 2019
Published date: 15 February 2020
Keywords: 3D printing, Additive manufacturing, Cellulose acetate, Controlled release, Osmotic system, Personalized medicine, micro-Computed tomography

Identifiers

Local EPrints ID: 437209
URI: http://eprints.soton.ac.uk/id/eprint/437209
ISSN: 0928-0987
PURE UUID: fffb6b18-8232-4d51-9984-7aa4b7a00b53
ORCID for Orestis L Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147

Catalogue record

Date deposited: 21 Jan 2020 17:36
Last modified: 26 Nov 2021 05:36

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Contributors

Author: Christos I Gioumouxouzis
Author: Emmanouil Tzimtzimis
Author: Anthi Dourou
Author: Catherine Markopoulou
Author: Nikolaos Bouropoulos
Author: Dimitrios Tzetzis
Author: Dimitrios G Fatouros

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