ABSTRACT
Introduction ...................................................................................................................................... 74 Enhancement of Delivery of the Dose to the Skin ......................................................................... 75
Metering Valves............................................................................................................................. 75 Spray Pattern and Droplet Size .................................................................................................... 75
Applicator Design ..................................................................................................................... 75 Control of Area ............................................................................................................................. 75
Volume Delivered Per Unit Area.............................................................................................. 75 Containment of Spray............................................................................................................... 76 Minimizing Nonproductive Loss .............................................................................................. 76
Enhancement of Delivery into the Stratum Corneum..................................................................... 76 Topology of Skin Surface ............................................................................................................. 76 Sebum ........................................................................................................................................... 77 Available Area ............................................................................................................................... 78 Increase in Thermodynamic Activity of Drug ............................................................................. 78
Evaporation of the Volatile Component of the Vehicle .......................................................... 78 Choice of Nonvolatile Solvent.................................................................................................. 78 Increasing the Solubility of Drug in the Stratum Corneum .................................................... 78
Enhancement of Permeation through Skin ..................................................................................... 79 Solvent Drag ................................................................................................................................. 79 Effect on Lipid Arrangement ........................................................................................................ 79 Extraction of Lipids....................................................................................................................... 79 Selective Extraction of Cholesterol .............................................................................................. 79
Enhancement of Bioavailability ....................................................................................................... 80
Characteristics of Solvents and Enhancers Required for Metered Dose Spray Delivery ............... 80 Volatile Solvent ............................................................................................................................. 80 Nonvolatile Solvent....................................................................................................................... 80 Penetration Enhancer ................................................................................................................... 81
References......................................................................................................................................... 81
There has been much published regarding the enhancement of transdermal penetration using chemical penetration enhancers.1 However, most of the studies have focused on how a particular chemical can change the permeation rate of drugs across the stratum corneum from solutions of drugs where an ‘‘infinite’’ dose is used.2 The point of many of these studies is to investigate the mechanisms of enhancement3,4 and structureactivity relationships.5-8 Much less has been published regarding the measurement of enhanced permeation from commercially viable preparations in vivo. Studies using skin blanching as a measure of penetration have been performed.9 Use has also been made of noninvasive techniques such as ATR FTIR to measure the enhancement of penetration into the stratum corneum in vivo.10 This review canvasses the strategies that have been employed with a particular delivery system namely a metered dose transdermal spray.
