title: New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer.
abstract: 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.
authors.affiliation: Université Lille 1, Unité Matériaux et Transformations (UMET) UMR CNRS 8207, Villeneuve d'Ascq, France; Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Garcia-Fernandez
authors.affiliation: Université Lille 1, Unité Matériaux et Transformations (UMET) UMR CNRS 8207, Villeneuve d'Ascq, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tabary
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
authors.forename: Feng
authors.initials: F
authors.lastname: Chai
authors.affiliation: Université Lille 1, Unité Matériaux et Transformations (UMET) UMR CNRS 8207, Villeneuve d'Ascq, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cazaux
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchemain
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Flament
authors.affiliation: Université Lille 1, Unité Matériaux et Transformations (UMET) UMR CNRS 8207, Villeneuve d'Ascq, France. Electronic address: bernard.martel@univ-lille1.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Martel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002482:Cellulose / Q000737:chemistry* / Q000633:toxicity; D019343:Citric Acid / Q000737:chemistry* / Q000633:toxicity; D003505:Cyclodextrins / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D013607:Tablets; C041953:cyclodextrin polymer; D019343:Citric Acid; D002482:Cellulose
keywords: Acute toxicity; Beta-cyclodextrin (PubChem CID: 101136808); Citric acid monohydrate (PubChem CID: 22230); Cycloheptaamylose; Direct compression; Multifunctional excipient; Tablets; β-Cyclodextrin polymer