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

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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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Abbreviations

CBZ-GLA :

Carbamazepine glutaric acid cocrystal

CBZ :

Carbamazepine

GLA :

Glutaric acid

PXRD :

Powder X-ray diffraction

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Acknowledgements and Disclosures

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).

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Authors and Affiliations

  1. Pharmaceutical Science & Technology Laboratories, Pharmaceutical Technology, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, 305-8585, Japan

    Hiroyuki Yamashita

  2. Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall 308 Harvard Street S.E., Minneapolis, Minnesota, 55455, USA

    Hiroyuki Yamashita & Changquan Calvin Sun

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  1. Hiroyuki Yamashita
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  2. Changquan Calvin Sun
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Correspondence to Changquan Calvin Sun.

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Yamashita, H., Sun, C.C. Material-Sparing and Expedited Development of a Tablet Formulation of Carbamazepine Glutaric Acid Cocrystal– a QbD Approach. Pharm Res 37, 153 (2020). https://doi.org/10.1007/s11095-020-02855-3

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