Fabrication of extended-dissolution divalproex tablets: a green solvent-free granulation technique

Objective: Divalproex sodium (DVS) is a challenging drug owing to its hygroscopicity, bitter taste, and short in vivo half-life. This study aims to produce stable taste masked DVS once daily tablets using solvent free hot melt granulation (HMG) process. Methods: A lab scale high shear mixer granulat...

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Bibliographic Details
Published in:Drug development and industrial pharmacy 2020-06, Vol.46 (6), p.975-987
Main Authors: Khaled, Amr, Abdel-Hamid, Sameh, Nasr, Maha, Sammour, Omaima A.
Format: Article
Language:English
Subjects:
Divalproex sodium
Drug Compounding
Excipients
extended dissolution
hot melt granulation
lipid matrix
moisture sensitive
Solubility
solvent free
Solvents - chemistry
Tablets - chemistry
taste masking
Valproic Acid
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Summary:Objective: Divalproex sodium (DVS) is a challenging drug owing to its hygroscopicity, bitter taste, and short in vivo half-life. This study aims to produce stable taste masked DVS once daily tablets using solvent free hot melt granulation (HMG) process. Methods: A lab scale high shear mixer granulator employing six meltable lipid binders (compritol ® 888 ATO, beeswax, gelucire ® 50/13, precirol ® ATO5, stearyl alcohol, and geleol ® ) was used for the preparation of tablets. Quality control tests were performed on granules and tablets, and Box-Behnken's design was adopted to investigate the effect of binder concentration, impeller speed, and granulation time on the drug dissolution. Shelf and accelerated stability evaluation, taste assessment, and in vivo pharmacokinetic study were conducted on the selected batches. Results: Results revealed that DVS tablets were successfully prepared, and that the in vitro dissolution of the drug was inversely proportional to the binder concentration. Beeswax and compritol ® tablets showed similar dissolution profiles to the marketed product Depakote ® 500 ER tablets (F1  50). The selected batches showed lower moisture content (
ISSN:0363-9045
1520-5762
DOI:10.1080/03639045.2020.1764023