title: Topical corticosteroid delivery into human skin using hydrofluoroalkane metered dose aerosol sprays.
abstract: Drug loaded hydrofluoroalkane (HFA) sprays can generate effective pharmaceutical formulations, but a deeper understanding of the manner in which these dynamic systems drive the process of in situ semi-solid dosage form assembly is required. The aim of this study was to investigate the effect of the matrix assembly and composition on drug localisation in human skin. Comparing the characteristics of sprays constituting HFA 134a, ethanol (EtOH), poly(vinyl pyrrolidone) K90, isopropyl myristate (IPM), and poly(ethylene glycol) (PEG) demonstrated that the addition of non-volatile solvents acted to delay EtOH evaporation, control the degree of drug saturation (DS) and enhance the corticosteroid delivery from HFA spray formulations. In a dose matched skin penetration study the HFA sprays containing only EtOH as a co-solvent delivered 2.1 μg BMV (DS 13.5) into the tissue, adding IPM to the EtOH HFA delivered 4.03 μg BMV (DS 11.2), whist adding PEG to the EtOH HFA delivered 6.1 μg BMV (DS 0.3). Compared to commercial cream (delivering 0.91 μg BMV) the EtOH/PEG HFA spray deposited over 6 times (p<0.05) more drug into the skin. Post spray deposition characterisation of the semi-solid suggested that the superior performance of the EtOH/PEG HFA spray was a consequence of retarding EtOH evaporation and presenting the drug in an EtOH rich PEG residual phase, which promoted BMV passage through the SC and into epidermis.
authors.affiliation: Institute of Pharmaceutical Science, King's College, London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Reid
authors.forename: Faiza
authors.initials: F
authors.lastname: Benaouda
authors.forename: Rajeshree
authors.initials: R
authors.lastname: Khengar
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Jones
authors.forename: Marc B
authors.initials: MB
authors.lastname: Brown
mesh_terms: D000287:Administration, Topical; D000335:Aerosol Propellants / Q000008:administration & dosage*; D000336:Aerosols; D001507:Beclomethasone / Q000008:administration & dosage* / Q000737:chemistry; D001624:Betamethasone Valerate / Q000008:administration & dosage* / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D066298:In Vitro Techniques; D036501:Metered Dose Inhalers; D009226:Myristates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000336:Aerosols; D001507:Beclomethasone; D001624:Betamethasone Valerate; D000431:Ethanol; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; D009226:Myristates; D011092:Polyethylene Glycols; D011145:Polyvinyls; D011759:Pyrrolidines; D012997:Solvents; C505150:poly(N-vinylpyrrolidine); C008205:isopropyl myristate; C094049:apaflurane; D005466:Fluorocarbons