title: Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.
abstract: Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Yellela S R
authors.initials: YS
authors.lastname: Krishnaiah
authors.forename: Usha
authors.initials: U
authors.lastname: Katragadda
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000279:Administration, Cutaneous; D003080:Cold Temperature; D016503:Drug Delivery Systems / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D012867:Skin / Q000187:drug effects
chemical_list: D000269:Adhesives
keywords: cold flow; drug delivery systems; drug-in-adhesive; imaging; method development; microscopy; physical characterization; skin; stereomicroscopic; transdermal