title: Formulation, stability and thermal analysis of lyophilised wound healing wafers containing an insoluble MMP-3 inhibitor and a non-ionic surfactant.
abstract: Lyophilised wafers are being developed as topical drug delivery systems for the treatment of chronic wounds. This study describes the formulation of xanthan wafers containing a selective, insoluble MMP-3 inhibitor (UK-370,106) and a non-ionic surfactant, designed to release accurate doses of UK-370,106 directly to a suppurating wound bed. Stability of UK-370,106 in the wafer compared to a non-lyophilised gel suspension was investigated using a combination of light scattering, thermal and microscopic techniques. Particle size distributions in UK-370,106-loaded wafers were constant throughout an accelerated stability study (12 weeks, 40 degrees C) while the mean particle size in a non-lyophilised suspension increased by 15 microm in the same period. Thermal analysis of UK-370,106-loaded wafers highlighted an unexpected interaction between the drug and the surfactant that was further investigated using simple mixtures of each component. It was concluded that an in situ solvate of UK-370,106 and the non-ionic surfactant can form and that this may have implications towards the stability of UK-370,106 during the formulation process. Further concerns regarding high water contents (14%) in the wafer and its effect on product stability were unfounded and it was concluded that these novel delivery systems provided a viable alternative to gel suspensions.
authors.affiliation: Department of Pharmaceutical Sciences, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, Glasgow G4 ONR, UK. k.h.matthews@rgu.ac.uk
authors.forename: K H
authors.initials: KH
authors.lastname: Matthews
authors.forename: H N E
authors.initials: HN
authors.lastname: Stevens
authors.forename: A D
authors.initials: AD
authors.lastname: Auffret
authors.forename: M J
authors.initials: MJ
authors.lastname: Humphrey
authors.forename: G M
authors.initials: GM
authors.lastname: Eccleston
mesh_terms: D002208:Caproates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005612:Freeze Drying; D005782:Gels; D061965:Matrix Metalloproteinase Inhibitors; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011083:Polycyclic Compounds; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
chemical_list: C476600:3-(((2,2-dimethyl-1-(((2-methoxy-1-phenylethyl)amino)carbonyl)propyl)amino)carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoic acid; D002208:Caproates; D004791:Enzyme Inhibitors; D005782:Gels; D061965:Matrix Metalloproteinase Inhibitors; D011083:Polycyclic Compounds; D011135:Polysaccharides, Bacterial; D013501:Surface-Active Agents; D020442:Poloxamer; D014633:Valine; C002563:xanthan gum