Pulmonary and nasal deposition of ketorolac tromethamine solution (SPRIX) following intranasal administration

Abstract

Ketorolac tromethamine is a racemic, non-steroidal, anti-inflammatory drug (NSAID). An intra-nasal (IN) formulation, SPRIX®, is approved for the treatment of short term (up to 5 days) acute moderate to moderately severe pain. The primary objective of this study was to determine whether 99mTc-diethylenetriaminepenta acetic acid (DTPA) radiolabelled ketorolac tromethamine formulation (31.5mg) was deposited in the lungs of healthy subjects (4 men and 9 women) following nasal inhalation of different intensities (gentle or vigorous sniff) and under different postural conditions (upright or semi-supine). The secondary objectives were to determine the deposition pattern of radiolabelled ketorolac solution in the nasal cavity and the clearance of the radiolabel over a 6h period post-administration. The nasal spray pump delivery device used showed a droplet size distribution with a volume mean diameter (VMD) of 50μm and approximately 85% of the aerosol mass contained in droplets >10μm diameter. The fraction of the dose recorded from the lung regions averaged <0.5%, and was considered to represent scattered radiation rather than true pulmonary deposition. This fraction was not affected by posture or by inhalation manoeuvre. The majority of the radiolabelled intranasal dose was deposited in the nasal cavity. The visual spread patterns within the nasal cavity were most uniform following administration in the upright position regardless of inhalation manoeuvre. Clearance from the nasal cavity was initially very rapid, with only 16–30% of the dose remaining after 10min and 6–14% after 6h. Retention was greatest following gentle inhalation.