Radiolabeling Method for Lyophilizate for Dry Powder Inhalation Formulations

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Apr 23

PMID 35456593

Authors

Kahori Miyamoto

Tomomi Akita

Chikamasa Yamashita

Affiliations

Soon will be listed here.

Abstract

Human lung deposition data is non-mandatory for drug approval but very useful for the development of orally inhaled drug products. Lung deposition of inhaled drugs can be quantified by radionuclide imaging, for which one of the first considerations is the method used to radiolabel formulations. In this study, we report the development of a radiolabeling method for lyophilizate for dry powder inhalation (LDPI) formulations. TechneCoat is one method that can radiolabel drug particles without using solvents. In this method, particles are radiolabeled with a dispersion of Tc-labeled nanoparticles called Technegas. Because a LDPI formulation is not comprised of particles but is a lyophilized cake aerosolized by air impact, the TechneCoat method cannot be used for the radiolabeling of LDPI formulations. We therefore modified the TechneCoat apparatus so that LDPI formulations were not aerosolized by the Technegas flow. Radiolabeling using a modified TechneCoat apparatus was validated with model LDPI formulations of interferon alpha (IFN). IFN of Tc-unlabeled, IFN of Tc-labeled, and Tc of Tc-labeled LDPI formulations showed similar behavior, and differences from IFN of Tc-unlabeled LDPI formulations were within ±15% in aerodynamic particle size distribution measurement. Our radiolabeling method for LDPI formulations may be useful for the quantification of drug deposition in human lungs.

Citing Articles

The effects of airway disease on the deposition of inhaled drugs.

Darquenne C, Corcoran T, Lavorini F, Sorano A, Usmani O Expert Opin Drug Deliv. 2024; 21(8):1175-1190.

PMID: 39136493 PMC: 11412782. DOI: 10.1080/17425247.2024.2392790.

References

Senden T, Moock K, Gerald J, Burch W, Browitt R, Ling C . The physical and chemical nature of technegas. J Nucl Med. 1997; 38(8):1327-33. View

Newman S . Can lung deposition data act as a surrogate for the clinical response to inhaled asthma drugs?. Br J Clin Pharmacol. 2000; 49(6):529-37. PMC: 2015044. DOI: 10.1046/j.1365-2125.2000.00106.x. View

Patton J, Byron P . Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov. 2006; 6(1):67-74. DOI: 10.1038/nrd2153. View

Dolovich M . In vitro measurements of delivery of medications from MDIs and spacer devices. J Aerosol Med. 1996; 9 Suppl 1:S49-58. DOI: 10.1089/jam.1996.9.suppl_1.s-49. View

Ohori R, Kiuchi S, Sugiyama S, Miyamoto K, Akita T, Yamashita C . Efficient optimization of high-dose formulation of novel lyophilizates for dry powder inhalation by the combination of response surface methodology and time-of-flight measurement. Int J Pharm. 2020; 581:119255. DOI: 10.1016/j.ijpharm.2020.119255. View

Stass H, Nagelschmitz J, Kappeler D, Sommerer K, Kietzig C, Weimann B . Ciprofloxacin Dry Powder for Inhalation in Patients with Non-Cystic Fibrosis Bronchiectasis or Chronic Obstructive Pulmonary Disease, and in Healthy Volunteers. J Aerosol Med Pulm Drug Deliv. 2016; 30(1):53-63. DOI: 10.1089/jamp.2015.1282. View

Miyamoto K, Yanagisawa M, Taga H, Yamaji H, Akita T, Yamashita C . Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory. Pharmaceutics. 2021; 13(5). PMC: 8145348. DOI: 10.3390/pharmaceutics13050632. View

Newman S, Pitcairn G, Hirst P, Rankin L . Radionuclide imaging technologies and their use in evaluating asthma drug deposition in the lungs. Adv Drug Deliv Rev. 2003; 55(7):851-67. DOI: 10.1016/s0169-409x(03)00081-4. View

Groneberg D, Witt C, Wagner U, Chung K, Fischer A . Fundamentals of pulmonary drug delivery. Respir Med. 2003; 97(4):382-7. DOI: 10.1053/rmed.2002.1457. View

10.

Evans C, Cipolla D, Chesworth T, Agurell E, Ahrens R, Conner D . Equivalence considerations for orally inhaled products for local action-ISAM/IPAC-RS European Workshop report. J Aerosol Med Pulm Drug Deliv. 2012; 25(3):117-39. DOI: 10.1089/jamp.2011.0968. View

11.

Newman S . Characteristics of radiolabelled versus unlabelled inhaler formulations. J Aerosol Med. 1996; 9 Suppl 1:S37-47. DOI: 10.1089/jam.1996.9.suppl_1.s-37. View

12.

Biddiscombe M, Meah S, Underwood S, Usmani O . Comparing lung regions of interest in gamma scintigraphy for assessing inhaled therapeutic aerosol deposition. J Aerosol Med Pulm Drug Deliv. 2011; 24(3):165-73. DOI: 10.1089/jamp.2010.0845. View

13.

Bajracharya R, Song J, Back S, Han H . Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Comput Struct Biotechnol J. 2020; 17:1290-1308. PMC: 6944732. DOI: 10.1016/j.csbj.2019.09.004. View

14.

Miyamoto K, Ishibashi Y, Akita T, Yamashita C . Systemic Delivery of hGhrelin Derivative by Lyophilizate for Dry Powder Inhalation System in Monkeys. Pharmaceutics. 2021; 13(2). PMC: 7914841. DOI: 10.3390/pharmaceutics13020233. View

15.

Borgstrom L, Newman S, Weisz A, Moren F . Pulmonary deposition of inhaled terbutaline: comparison of scanning gamma camera and urinary excretion methods. J Pharm Sci. 1992; 81(8):753-5. DOI: 10.1002/jps.2600810807. View

16.

Labiris N, Dolovich M . Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003; 56(6):588-99. PMC: 1884307. DOI: 10.1046/j.1365-2125.2003.01892.x. View

17.

Newman S, Wilding I, Hirst P . Human lung deposition data: the bridge between in vitro and clinical evaluations for inhaled drug products?. Int J Pharm. 2000; 208(1-2):49-60. DOI: 10.1016/s0378-5173(00)00538-x. View

18.

Snell N, Ganderton D . Assessing lung deposition of inhaled medications. Consensus statement from a workshop of the British Association for Lung Research, held at the Institute of Biology, London, U.K. on 17 April 1998. Respir Med. 1999; 93(2):123-33. DOI: 10.1016/s0954-6111(99)90302-5. View

19.

Longest P, Tian G, Walenga R, Hindle M . Comparing MDI and DPI aerosol deposition using in vitro experiments and a new stochastic individual path (SIP) model of the conducting airways. Pharm Res. 2012; 29(6):1670-88. DOI: 10.1007/s11095-012-0691-y. View

20.

Owens D . New horizons--alternative routes for insulin therapy. Nat Rev Drug Discov. 2002; 1(7):529-40. DOI: 10.1038/nrd836. View