title: Drug release from Kollicoat SR 30D-coated nonpareil beads: evaluation of coating level, plasticizer type, and curing condition.
abstract: A newly available polyvinylacetate aqueous dispersion, Kollicoat SR 30D, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound (diphenhydramine hydrochloride) from nonpareil-based systems. Kollicoat SR 30D premixed with a selected plasticizer (10% wt/wt propylene glycol, 2.5% triethyl citrate, or 2.5% dibutyl sebacate), talc, and red #30 lake dye was coated onto the drug beads in an Aeromatic Strea I fluid-bed drier with a Wurster insert using bottom spray. With propylene glycol as the plasticizer, increases in polymer coating level retarded drug release from beads in a stepwise fashion along with apparent permeability, indicating a consistent release mechanism. Stability studies at 40 degrees C/75% RH revealed gradual decreases in dissolution rate, and additional curing studies further confirmed the dependence of release kinetics on curing condition. Furthermore, the type of plasticizer was found to play a key role. Unplasticized formulations exhibited the fastest dissolution, followed by formulations plasticized with triethyl citrate, propylene glycol, and dibutyl sebacate. All 4 formulations (unplasticized and plasticized), nevertheless, revealed a marked difference between uncured and cured dissolution profiles. Kollicoat SR 30D has, thereby, been demonstrated to effectively retard drug release from nonpareil-based systems. However, selected plasticizer type and subsequent curing condition play important roles in controlling drug release from such a system.
authors.affiliation: Formulation R&D, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. z.jesse.shao@pfizer.com
authors.forename: Zezhi J
authors.initials: ZJ
authors.lastname: Shao
authors.forename: Luis
authors.initials: L
authors.lastname: Moralesi
authors.forename: Steven
authors.initials: S
authors.lastname: Diaz
authors.forename: Nouman A
authors.initials: NA
authors.lastname: Muhammadi
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations; D004155:Diphenhydramine / Q000378:metabolism*; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D008863:Microspheres; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D010784:Photomicrography / Q000379:methods; D010968:Plasticizers / Q000378:metabolism*; D011145:Polyvinyls / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000085:Acetates; D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D010968:Plasticizers; D011145:Polyvinyls; D013608:Tablets, Enteric-Coated; D004155:Diphenhydramine; D002482:Cellulose