title: Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro-in vivo evaluations.
abstract: The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly.
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA.
authors.forename: Manjeet B
authors.initials: MB
authors.lastname: Pimparade
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Morott
authors.affiliation: College of Pharmacy, Sahm Yook University, Seoul 139-742, South Korea.
authors.forename: Jun-Bom
authors.initials: JB
authors.lastname: Park
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA.
authors.forename: Vijay I
authors.initials: VI
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, USA.
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Murthy
authors.affiliation: Ashland Specialty Ingredients, Global Pharma R&D, Wilmington, USA.
authors.forename: Zhuoyang
authors.initials: Z
authors.lastname: Lian
authors.affiliation: Ashland Specialty Ingredients, Global Pharma R&D, Wilmington, USA.
authors.forename: Elanor
authors.initials: E
authors.lastname: Pinto
authors.affiliation: Ashland Specialty Ingredients, Global Pharma R&D, Wilmington, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Bi
authors.affiliation: Ashland Specialty Ingredients, Global Pharma R&D, Wilmington, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Durig
authors.affiliation: Institute for Drug Delivery and Biomedical Research, Bangalore, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Murthy
authors.affiliation: Institute for Drug Delivery and Biomedical Research, Bangalore, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Shivakumar
authors.affiliation: Visveswarapuram Institute of Pharmaceutical Sciences, Bangalore, India.
authors.forename: K
authors.initials: K
authors.lastname: Vanaja
authors.affiliation: Visveswarapuram Institute of Pharmaceutical Sciences, Bangalore, India.
authors.forename: P C
authors.initials: PC
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, USA. Electronic address: marepka@olemiss.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D002110:Caffeine / Q000009:adverse effects* / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D002951:Citrates / Q000009:adverse effects* / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D010968:Plasticizers; D012995:Solubility; D013607:Tablets; D013649:Taste / Q000187:drug effects*; D055697:Taste Perception
chemical_list: D002951:Citrates; D004337:Drug Carriers; D010968:Plasticizers; D013607:Tablets; D002110:Caffeine; C013517:ethyl cellulose; D002482:Cellulose; C026189:caffeine citrate
keywords: Ethylcellulose (EC); Hot-melt extrusion; Modified screw design; Pediatric and geriatric; Taste-masking