Personalized Medicine in Nasal Delivery: The Use of Patient-Specific Administration Parameters to Improve Nasal Drug Targeting Using 3D-Printed Nasal Replica Casts

Zachary N. Warnken, Hugh D.C. Smyth, Daniel A. Davis, Steven D Weitman, John G. Kuhn, Robert O. Williams

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Effective targeting of nasal spray deposition could improve local, systemic, and CNS drug delivery; however, this has proven to be difficult due to the anatomical features of the nasal cavity, including the nasal valve and turbinate structures. Furthermore, nasal cavity geometries and dimensions vary between individuals based on differences in their age, gender, and ethnicity. The effect of patient-specific administration parameters was evaluated for their ability to overcome the barriers of targeted nasal drug delivery. The nasal spray deposition was evaluated in 10 3D-printed nasal cavity replicas developed based on the CT-scans of five pediatric and five adult subjects. Cromolyn sodium nasal solution, USP, modified with varying concentrations of hypromellose was utilized as a model nasal spray to evaluate the deposition pattern from formulations producing a variety of plume angles. A central composite design of experiments was implemented using the formulation with the narrowest plume angle to determine the patient-specific angle for targeting the turbinate region in each individual. The use of the patient-specific angle with this formulation significantly increased the turbinate deposition efficiency compared to that found for all subjects using an administration angle of 30°, around 90% compared to about 73%. Generally, we found turbinate deposition increased with decreases in the administration angle. Deposition to the upper regions of the replica was poor with any formulation or administration angle tested. Effective turbinate targeting of nasal sprays can be accomplished with the use of patient-specific administration parameters in individuals. Further research is required to see if these parameters can be device-controlled for patients and if other regions can be effectively targeted with other nasal devices.

Original languageEnglish (US)
Pages (from-to)1392-1402
Number of pages11
JournalMolecular Pharmaceutics
Volume15
Issue number4
DOIs
StatePublished - Apr 2 2018

Keywords

  • deposition pattern
  • intranasal administration
  • Nasal drug delivery
  • nasal spray
  • personalized medicine
  • spray angle

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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