title: The butterfly effect: a physical phenomenon of hypromellose matrices during dissolution and the factors affecting its occurrence.
abstract: A phenomenon was observed for the behavior of hypromellose matrices during dissolution. The tablet laminated radially, with both edges curled outwards, forming a "butterfly" shape. The butterfly effect is thus coined to describe this behavior. Due to the flamboyant shape assumed by the hydrated matrix, the apparent surface area for drug release was significantly increased. This study attempted to elucidate mechanistically the cause of this butterfly effect. Two formative mechanisms were proposed based on the behavior of moving solvent fronts and the anisotropic expansion of materials in solution. It was hypothesized that the particle size of hypromellose, applied compaction force used and proportions of both insoluble and soluble excipients contributed to the butterfly effect. The influence of the expanded shape on the mechanism and rate of drug release was also investigated. Matrix formulation was an important factor. Greater drug release was observed when the butterfly-shaped hydrated matrix was formed. The drug release profiles generally fitted the Higuchi and Korsmeyer-Peppas equations, indicating a combination of both diffusion and erosional drug release mechanisms. A combination of both fine and coarse hypromellose size fractions and adequate compaction force (more than 3 kN) were necessary for the manifestation of the butterfly effect.
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Cahyadi
authors.forename: L W
authors.initials: LW
authors.lastname: Chan
authors.forename: P
authors.initials: P
authors.lastname: Colombo
authors.forename: P W S
authors.initials: PW
authors.lastname: Heng
mesh_terms: D016880:Anisotropy; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D005480:Flurbiprofen / Q000737:chemistry; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D010316:Particle Size; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013607:Tablets; D013997:Time Factors
chemical_list: D005079:Excipients; D012997:Solvents; D013607:Tablets; D065347:Hypromellose Derivatives; D005480:Flurbiprofen; D008747:Methylcellulose