title: Insight Into a Novel Strategy for the Design of Tablet Formulations Intended for Direct Compression.
abstract: In a recent study, it was demonstrated that improving flow of a model poorly flowing and poorly compactable drug substance, acetaminophen, via dry coating while using fine excipients, may promote direct compression. To validate this novel strategy, particularly for high drug-loading formulations, this study investigates the effect of microcrystalline cellulose (MCC) particle size and dry coating on powder tabletability and flowability. It was determined that blends containing fine-sized MCC (20 μm) resulted in the highest tablet tensile strength and best tabletability because it provides higher interparticle contact area compared with coarse-sized MCC. Although tabletability can be improved using fine MCC, flowability is poor but can be improved through dry coating, a process that coats glidants (nano-sized silica) onto particle surfaces. To retain the tabletability, which was adversely affected because of the presence of glidant in the blend, while simultaneously enhancing flowability via dry coating, separately blending the drug substance with glidant is shown to be the best method of processing. The combined use of fine excipients and selective dry coating offers a novel and advantageous formulation strategy in comparison with the conventional use of coarse excipients, such as Avicel PH 102, that have been designed and marketed for direct compression.
authors.affiliation: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064. Electronic address: maxx.capece@abbvie.com.
authors.forename: Maxx
authors.initials: M
authors.lastname: Capece
authors.affiliation: Department of Chemical, Pharmaceutical, and Biological Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Chemical, Pharmaceutical, and Biological Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Davé
mesh_terms: D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry; D013499:Surface Properties; D013607:Tablets / Q000737:chemistry*; D013718:Tensile Strength
chemical_list: D005079:Excipients; D013607:Tablets; D012822:Silicon Dioxide; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: direct compression; dry coating; formulation development; tabletability; tableting