title: Evaluation of different formulation studies on air-filled polymeric microcapsules by multivariate analysis.
abstract: Air-filled polymeric microcapsules have been prepared by freeze-drying of emulsions containing the wall-forming polymer in the organic phase of oil in water emulsions. Echogenic air-filled microcapsules were prepared from emulsions containing either (-)-camphene, cyclohexane or cyclooctane as the solvent in the organic phase. Formulation studies have been performed to improve the yield and acoustic quality of the microcapsule suspensions. The yield was measured as particle concentration or efficacy, i.e. normalised attenuation at 3.5 MHz, related to the amount of polymer used. No overall conclusion could be made for all the variables when visually comparing the results from the different investigations. Multivariate analyses (PCA and PLS) were therefore necessary to be able to reveal any relevant systematic information from all the investigations. Different parameters describing the formulation, the production process and parameters describing the characterisation of the intermediates and the final product were set as independent X-variables. Three to four percent (w/v) of polymer was found to be the appropriate concentration of wall forming polymer. Including PEG 3000 resulted in improved freeze-dried product and suspension. Quenching of the emulsions by freezing in dry ice/methanol prior to freeze-drying was not necessary. Process parameters for homogenising and freeze-drying should be optimised with regard to the single systems, due to the different physico-chemical properties of the different solvents, especially melting point and vapour pressure.
authors.affiliation: Amersham Health A.S., P.O. Box 4220, Nydalen, N-04011 Oslo, Norway. Kathrin.bjerknes@amersham.com
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bjerknes
authors.forename: Jorunn Undheim
authors.initials: JU
authors.lastname: Braenden
authors.forename: Gro
authors.initials: G
authors.lastname: Smistad
authors.forename: Irenè
authors.initials: I
authors.lastname: Agerkvist
mesh_terms: D000388:Air; D000081008:Bicyclic Monoterpenes; D002626:Chemistry, Pharmaceutical; D003510:Cyclohexanes / Q000008:administration & dosage; D004655:Emulsions; D005612:Freeze Drying; D015999:Multivariate Analysis; D011108:Polymers / Q000008:administration & dosage*; D013729:Terpenes / Q000008:administration & dosage
chemical_list: D000081008:Bicyclic Monoterpenes; D003510:Cyclohexanes; D004655:Emulsions; D011108:Polymers; D013729:Terpenes; C019286:camphene