title: Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation.
abstract: Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol® ATO 888, Precirol® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p=0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p=0.028) and the type of hydrophilic polymer with polymer ratio (p=0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore. Electronic address: cheng.tan@abbvie.com.
authors.forename: David Cheng Thiam
authors.initials: DC
authors.lastname: Tan
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
authors.forename: William Wei Lim
authors.initials: WW
authors.lastname: Chin
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
authors.forename: En Hui
authors.initials: EH
authors.lastname: Tan
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Hong
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: AbbVie Pte Ltd, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore. Electronic address: rajeev.gokhale@abbvie.com.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gokhale
mesh_terms: D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D011108:Polymers / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D014700:Verapamil / Q000737:chemistry*
chemical_list: D005079:Excipients; D011108:Polymers; D013607:Tablets; D014700:Verapamil
keywords: Direct mold; Hot melt extruder; Hydrophilic; Hydrophobic; Melt granulation; Modified release