Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal– a QbD Approach

Hiroyuki Yamashita; Changquan Calvin Sun

doi:10.1007/s11095-020-02855-3

Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal– a QbD Approach

Hiroyuki Yamashita, Changquan Calvin Sun

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Purpose: To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution. Methods: The carbamazepine – glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons. Results: A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution. Conclusion: The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.

Original language	English (US)
Article number	153
Journal	Pharmaceutical research
Volume	37
Issue number	8
DOIs	https://doi.org/10.1007/s11095-020-02855-3
State	Published - Aug 1 2020

Bibliographical note

Funding Information:
Parts of this work were carried out in the Characterization Facility, University of Minnesota, a member of the NSF-funded Materials Research Facilities Network (http://www.mrfn.org) through the UMN MRSEC (DMR-1420013).

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

cocrystal
formulation development
manufacturability
material-sparing
quality by design
tablet

PubMed: MeSH publication types

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title = "Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal– a QbD Approach",

abstract = "Purpose: To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution. Methods: The carbamazepine – glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons. Results: A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution. Conclusion: The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.",

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N2 - Purpose: To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution. Methods: The carbamazepine – glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons. Results: A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution. Conclusion: The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.

AB - Purpose: To efficiently develop a tablet formulation of carbamazepine using a soluble cocrystal with excess coformer to maintain phase stability during dissolution. Methods: The carbamazepine – glutaric acid cocrystal (CBZ-GLA, 1:1) and excess glutaric acid (GLA) were mixed with suitable tablet excipients, which were selected to address powder flowability and tabletability deficiencies specifically. Tablet friability and dissolution profiles were evaluated to guide formulation optimization. Dry granules were prepared by milling simulated ribbons. Results: A binary blend of CBZ-GLA and GLA had poor flowability and marginal tabletability. Therefore, silica coated Avicel PH-102 (sMCC) was applied as a binder to improve the flow property and tabletability. A formulation consisting of sMCC, CBZ-GLA, and GLA exhibited good manufacturability but did not show improved dissolution because of rapid precipitation of CBZ dihydrate when CBZ-GLA came in contact with water. Dry granulation of CBZ-GLA and GLA dramatically improved dissolution profile due to the intimate contact between CBZ-GLA and GLA. Such cocrystal - coformer granules also led to much improved tablet manufacturability and dissolution. Conclusion: The successful tablet development of CBZ-GLA, using < 3 g of the cocrystal in <3 weeks, demonstrates an efficient workflow for tablet formulation development based on material-sparing and predictive powder characterization techniques. This workflow is useful for early tablet development using enabling solid form, such as cocrystal, when only a small amount of material is available.

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KW - quality by design

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Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal– a QbD Approach

Abstract

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