(459) Evaluation of liquid spray technology for sublingual drug delivery

Abstract

Sublingual drug administration may be appropriate in multiple disease states, such as in patients who require rapid onset of effect (eg, transmucosal immediate-release fentanyl for breakthrough cancer pain [fentanyl sublingual spray]) or have conditions that negatively impact oral medication administration (eg, dysphagia, xerostomia), or when hepatic first-pass metabolism avoidance is desired. It is important for a sublingual spray device to accurately deliver microliter quantities of appropriate droplet size (eg, to prevent lung deposition) and have a simple, easy-to-use, durable mechanical design (eg, no springs). This study evaluated the characteristics of liquid spray technology for sublingual delivery. Two formulations (A and B) were evaluated and contained 30% v/v dehydrated alcohol, 5% v/v propylene glycol, 0.2% v/v peppermint oil, pH 9 borate buffer (quantity sufficient), and hydroxypropyl-beta-cyclodextrin (1:2); formulation B also contained 1% v/v hydroxypropyl cellulose (HPC-EP). Formulations were sprayed using a 0.1-mL multidose pump and evaluated for dose volume, spray pattern (methylene blue added; actuation 30 mm from target), and droplet size distribution using a Malvern Mastersizer particle size analyzer (n=25 spray samples). For formulations A and B, dose volumes were similar (mean volume, 100.4 and101.5 microliters, respectively; maximum single volume, 103.2 and 103.7 microliters). Spray patterns varied only slightly for formulations A versus B (small diameter mean [range], 50.6 millimeters [35.4-62.0] vs 34.0 millimeters [29-46.0], respectively; mean ratio largest/smallest diameter [range], 1.1 [1.0-1.3] vs 1.2 [1.1-1.5]). However, droplet size distribution varied with formulation A versus B (mean percentage share of droplet diameters at 10 micrometers [range], 1.7 [0.7-2.7] vs 0.7 [0.2-1.3], respectively). Overall, the characteristics of a liquid spray technology support further development for sublingual drug delivery. A formulation of fentanyl for sublingual administration is currently available, and research evaluating additional pain or addiction pharmacologic candidates for sublingual delivery in pain-related and other conditions is warranted. Supported by Insys Therapeutics. Sublingual drug administration may be appropriate in multiple disease states, such as in patients who require rapid onset of effect (eg, transmucosal immediate-release fentanyl for breakthrough cancer pain [fentanyl sublingual spray]) or have conditions that negatively impact oral medication administration (eg, dysphagia, xerostomia), or when hepatic first-pass metabolism avoidance is desired. It is important for a sublingual spray device to accurately deliver microliter quantities of appropriate droplet size (eg, to prevent lung deposition) and have a simple, easy-to-use, durable mechanical design (eg, no springs). This study evaluated the characteristics of liquid spray technology for sublingual delivery. Two formulations (A and B) were evaluated and contained 30% v/v dehydrated alcohol, 5% v/v propylene glycol, 0.2% v/v peppermint oil, pH 9 borate buffer (quantity sufficient), and hydroxypropyl-beta-cyclodextrin (1:2); formulation B also contained 1% v/v hydroxypropyl cellulose (HPC-EP). Formulations were sprayed using a 0.1-mL multidose pump and evaluated for dose volume, spray pattern (methylene blue added; actuation 30 mm from target), and droplet size distribution using a Malvern Mastersizer particle size analyzer (n=25 spray samples). For formulations A and B, dose volumes were similar (mean volume, 100.4 and101.5 microliters, respectively; maximum single volume, 103.2 and 103.7 microliters). Spray patterns varied only slightly for formulations A versus B (small diameter mean [range], 50.6 millimeters [35.4-62.0] vs 34.0 millimeters [29-46.0], respectively; mean ratio largest/smallest diameter [range], 1.1 [1.0-1.3] vs 1.2 [1.1-1.5]). However, droplet size distribution varied with formulation A versus B (mean percentage share of droplet diameters at 10 micrometers [range], 1.7 [0.7-2.7] vs 0.7 [0.2-1.3], respectively). Overall, the characteristics of a liquid spray technology support further development for sublingual drug delivery. A formulation of fentanyl for sublingual administration is currently available, and research evaluating additional pain or addiction pharmacologic candidates for sublingual delivery in pain-related and other conditions is warranted. Supported by Insys Therapeutics.