New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer

• Published in: International journal of pharmaceutics 2016-09, Vol.511 (2), p.913-920
• Main Authors: Garcia-Fernandez, Maria José, Tabary, Nicolas, Chai, Feng, Cazaux, Frédéric, Blanchemain, Nicolas, Flament, Marie-Pierre, Martel, Bernard
• Format: Article
• Language: English
• Subjects: Acute toxicity; Animals; Body Weight - drug effects; Body Weight - physiology; Cellulose - chemistry; Cellulose - toxicity; Citric Acid - chemistry; Citric Acid - toxicity; Cyclodextrins - chemistry; Cyclodextrins - toxicity; Direct compression; Drug Compounding; Excipients - chemistry; Excipients - toxicity; Multifunctional excipient; Particle Size; Rats; Rats, Sprague-Dawley; Tablets; X-Ray Diffraction; β-Cyclodextrin polymer
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.07.059

[Display omitted] A β-cyclodextrin (β-CD) polymer obtained by crosslinking β-CD with citric acid in its water-insoluble (PCD-I) and soluble (PCD-S) forms was used as a multifunctional direct compression excipient for tablet designing. PCD-I powder was obtained after grinding the solid fraction through a 200μm grid. PCD-S powder was recovered after lyophilization or spray drying of the PCD-S aqueous solutions, eventually followed by a wet granulation step. Both PCD-I and PCD-S powders were characterized, separately and mixed in variable ratios, based on dynamic water vapor sorption, SEM, particle size distribution, tapped density, compressibility, and flowability. PCD-I and spray dried and lyophilized/wet granulated PCD-S, as well as the mixture PCD-I/PCD-S=90/10, presented optimal free flowing characteristics. Then, PCD-I or PCD-S powders - separately or mixed in variable ratios - were used for tablets preparation by direct compression without adding any other excipient (e.g. binder, lubricant, disintegrant etc). As PCD-I decreased, tablets resistance to crushing and disintegration time increased from 15s to 15min (against 30min for β-CD), showing the improved disintegrant functionality of PCD-I, that rapidly swelled once in contact with water. Finally, PCD was force-fed to Sprague-Dawley rats (2g/kg) which were then observed during 14days for any clinical signs of toxicity.