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

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 excipi...

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Bibliographic Details
Published in:Pharmaceutical research 2020-08, Vol.37 (8), p.153-153, Article 153
Main Authors: Yamashita, Hiroyuki, Sun, Changquan Calvin
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Carbamazepine
Carbamazepine - chemistry
Carbamazepine - pharmacology
Cellulose - chemistry
Crystallization
Dissolution
Drug Compounding
Excipients - chemistry
Glutarates - chemistry
Glutarates - pharmacology
Medical Law
Pharmacology/Toxicology
Pharmacy
Phase Transition
Powders
Research Paper
Silicon Dioxide - chemistry
Solubility
Tablets - chemistry
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Summary: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
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-020-02855-3