Skip to main content

Advertisement

Log in

Recent developments in dry powder inhalation (DPI) formulations for lung-targeted drug delivery

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Background

Dry powder inhalation (DPI) formulations have been widely studied for the treatment of respiratory diseases, including COVID-19, which have become common and dangerous worldwide. Dry powder inhalation formulations have become a popular approach for targeted drug delivery to the lungs. Inhalation offers advantages over other administration routes by providing direct treatment and action to alleviate and manage respiratory conditions.

Area covered

This review covers the anatomical and physiological characteristics of the human respiratory tract and the considerations that need to be considered when formulating DPIs. It also provides an overview of current inhalation products and clinical trials in the treatment of respiratory diseases such as asthma, COPD, IPF, PAH, tuberculosis, and COVID-19. Additionally, various methods of particle preparation for DPI formulations are described, including conventional techniques such as milling and spray drying, and novel techniques such as SFD, SCF, TFF, HME, and PRINT.

Expert opinion

DPIs are typically prepared by using conventional and novel particle preparation techniques, but these methods may require specialized equipment and have some limitations. Moreover, the number of approved inhalable excipients is limited, which hinders further development of DPI formulations. To address this, the development and approval of new inhalable excipients is needed, and the use of new technologies and excipients is expected to overcome the limitations of DPI formulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Asthma U http://www.asthma.org.uk/about/media/facts‐and‐statistics

  • Begat P et al (2005) The influence of force control agents on the cohesive-adhesive balance in dry powder inhaler formulations. Kona Powder Part J 23:109–121

    Article  CAS  Google Scholar 

  • Begat P et al (2009) The role of force control agents in high-dose dry powder inhaler formulations. J Pharm Sci 98(8):2770–2783

    Article  CAS  PubMed  Google Scholar 

  • Benza RL et al (2022) Safety and efficacy of RT234 vardenafil inhalation powder on exercise parameters in pulmonary arterial hypertension: phase II, dose-escalation study design. Respir Res 23(1):355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borna E et al (2019) Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016. Allergy 74(9):1703–1715

    Article  PubMed  Google Scholar 

  • Bosquillon C et al (2001) Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J Control Rel 70(3):329–339

    Article  CAS  Google Scholar 

  • Broadhead J et al (2011) The effect of process and formulation variables on the properties of spray-dried β-galactosidase. J Pharm Pharmacol 46(6):458–467

    Article  Google Scholar 

  • Burney P, Jarvis D, Perez-Padilla R (2015) The global burden of chronic respiratory disease in adults. Int J Tuberc Lung Dis 19(1):10–20

    Article  CAS  PubMed  Google Scholar 

  • Caimmi D, Martocq N, Trioleyre D, Guinet C, Godreuil S, Daniel T, Chiron R (2018) Positive effect of liposomal amikacin for inhalation on Mycobacterium abcessus in cystic fibrosis patients. Open Forum Infect Dis 5(3):ofy034

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan HK, Chew NY (2003) Novel alternative methods for the delivery of drugs for the treatment of asthma. Adv Drug Deliv Rev 55(7):793–805

    Article  CAS  PubMed  Google Scholar 

  • Cheow WS et al (2011) Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants. Int J Pharm 404(1):289–300

    Article  CAS  PubMed  Google Scholar 

  • Chow AHL et al (2007) Particle engineering for pulmonary drug delivery. Pharm Res 24(3):411–437

    Article  CAS  PubMed  Google Scholar 

  • Coelho MC, Harnby N (1978) Moisture bonding in powders. Powder Technol 20(2):201–205

    Article  Google Scholar 

  • Coppi G et al (2002) Alginate microparticles for enzyme peroral administration. Int J Pharm 242(1):263–266

    Article  CAS  PubMed  Google Scholar 

  • Costantino HR et al (2000) Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. Pharm Res 17(11):1374–1382

    Article  CAS  PubMed  Google Scholar 

  • Costantino HR et al (2002) Protein spray freeze drying. 2. Effect of formulation variables on particle size and stability. J Pharm Sci 91(2):388–395

    Article  CAS  PubMed  Google Scholar 

  • Cottin V et al (2018) Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 27(150):180076

    Article  PubMed  PubMed Central  Google Scholar 

  • D’Amato G et al (2019) Latest news on relationship between thunderstorms and respiratory allergy, severe asthma, and deaths for asthma. Allergy 74(1):9–11

    Article  PubMed  Google Scholar 

  • D’Alonzo GE et al (1991) Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 115(5):343–349

    Article  CAS  PubMed  Google Scholar 

  • Das SC et al (2011a) Determination of the polar and total surface energy distributions of particulates by inverse gas chromatography. Langmuir 27(2):521–523

    Article  CAS  PubMed  Google Scholar 

  • Das SC et al (2011b) Use of surface energy distributions by inverse gas chromatography to understand mechanofusion processing and functionality of lactose coated with magnesium stearate. Eur J Pharm Sci 43(4):325–333

    Article  CAS  PubMed  Google Scholar 

  • Debenedetti PG et al (1993) Rapid expansion of supercritical solutions (ress): fundamentals and applications. Fluid Phase Equilib 82:311–321

    Article  CAS  Google Scholar 

  • Depasquale R et al (2015) The influence of secondary processing on the structural relaxation dynamics of fluticasone propionate. AAPS PharmSciTech 16:589–600

    Article  CAS  PubMed  Google Scholar 

  • Emami F et al (2018) Drying technologies for the stability and bioavailability of biopharmaceuticals. Pharmaceutics 10(3):131

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  • Emery E et al (2009) Flowability of moist pharmaceutical powders. Powder Technol 189(3):409–415

    Article  CAS  Google Scholar 

  • Esfandiari N (2015) Production of micro and nano particles of pharmaceutical by supercritical carbon dioxide. J Supercrit Fluids 100:129–141

    Article  CAS  Google Scholar 

  • Esposito E et al (2000) Production of eudragit microparticles by spray-drying technique: influence of experimental parameters on morphological and dimensional characteristics. Pharm Dev Technol 5(2):267–278

    Article  CAS  PubMed  Google Scholar 

  • Etschmann C, Scherließ R (2022) Formulation of rifampicin softpellets for high dose delivery to the lungs with a novel high dose dry powder inhaler. Int J Pharm 617:121606

    Article  CAS  PubMed  Google Scholar 

  • Feeley JC et al (1998) Determination of surface properties and flow characteristics of salbutamol sulphate, before and after micronisation. Int J Pharm 172(1):89–96

    Article  CAS  Google Scholar 

  • Frost AE et al (2011) The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US Contemporary Registries. Chest 139(1):128–137

    Article  PubMed  Google Scholar 

  • Frumkin LR (2012) The pharmacological treatment of pulmonary arterial hypertension. Pharmacol Rev 64(3):583–620

    Article  CAS  PubMed  Google Scholar 

  • Galiè N et al (2016) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37(1):67–119

    Article  PubMed  Google Scholar 

  • Garcia A et al (2012) Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications. J Drug Deliv 2012:941243

    Article  PubMed  PubMed Central  Google Scholar 

  • Garwood P (2019) World no tobacco day 2019: don’t let tobacco take your breath away. World Health Organization, Geneva

    Google Scholar 

  • Global tuberculosis report (2019) World Health Organization. https://www.who.int/tb/publications/global_report/en/

  • Global Tuberculosis Report (2018) World Health Organization: www.who.int/tb/publications/global_report/en

  • Gradon L, Sosnowski TR (2014) Formation of particles for dry powder inhalers. Adv Powder Technol 25(1):43–55

    Article  CAS  Google Scholar 

  • Grenha A, Seijo B, Remuñán-López C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25(4):427–437

    Article  CAS  PubMed  Google Scholar 

  • Guo Y et al (2018) Genetic predisposition to obesity is associated with asthma in US Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos. Allergy 73(7):1547–1550

    Article  CAS  PubMed  Google Scholar 

  • Hasleton PS (1972) The internal surface area of the adult human lung. J Anat 112(3):391–400

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hassan MS, Lau RWM (2009) Effect of particle shape on dry particle inhalation: study of flowability, aerosolization, and deposition properties. AAPS PharmSciTech 10(4):1252–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haverich A, Scott W, Jamieson S (1985) Twenty years of lung preservation—a review. J Heart Transpl 4(2):234–240

    CAS  Google Scholar 

  • Hickey AJ, Mansour HM (2009) Delivery of drugs by the pulmonary route. In: Florence AT, Siepmann J (eds) Modern pharmaceutics. Taylor and Francis, Inc., New York, pp 191–219

    Google Scholar 

  • Ho R et al (2011) Role of surface chemistry and energetics in high shear wet granulation. Ind Eng Chem Res 50(16):9642–9649

    Article  CAS  Google Scholar 

  • Hoeper MM et al (2020) Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry. J Heart Lung Transpl 39(12):1435–1444

    Article  Google Scholar 

  • Hoppentocht M et al (2014) Technological and practical challenges of dry powder inhalers and formulations. Adv Drug Deliv Rev 75:18–31

    Article  CAS  PubMed  Google Scholar 

  • Horsfield K, Woldenberg MJ (1986) Branching ratio and growth of tree-like structures. Respir Physiol 63(1):97–107

    Article  CAS  PubMed  Google Scholar 

  • Houben RM, Dodd PJ (2016) The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 13(10):e1002152

    Article  PubMed  PubMed Central  Google Scholar 

  • Humbert M, Sitbon O, Simonneau G (2004) Treatment of pulmonary arterial hypertension. N Engl J Med 351(14):1425–1436

    Article  CAS  PubMed  Google Scholar 

  • Jain MS, Lohare GB, Bari M, Chavan R, Barhate SD, Shah CB (2011) Spray drying in pharmaceutical industry: a review. Res J Pharm Dosage Forms Technol 4(2):74–79

    Google Scholar 

  • Johnson KL, Kendall K, Roberts A (1971) Surface energy and the contact of elastic solids. Proc R Soc Lond A Math Phys Sci 324(1558):301–313

    CAS  ADS  Google Scholar 

  • Jud C et al (2013) Nanomaterials and the human lung: what is known and what must be deciphered to realise their potential advantages? Swiss Med Week 143:w13758

    Google Scholar 

  • Kaialy W, Nokhodchi A (2013) Treating mannitol in a saturated solution of mannitol: a novel approach to modify mannitol crystals for improved drug delivery to the lungs. Int J Pharm 448(1):58–70

    Article  CAS  PubMed  Google Scholar 

  • Kaialy W et al (2011) Effect of carrier particle shape on dry powder inhaler performance. Int J Pharm 421(1):12–23

    Article  CAS  PubMed  Google Scholar 

  • Kaialy W et al (2012a) Influence of lactose carrier particle size on the aerosol performance of budesonide from a dry powder inhaler. Powder Technol 227:74–85

    Article  CAS  Google Scholar 

  • Kaialy W, Ticehurst M, Nokhodchi A (2012b) Dry powder inhalers: mechanistic evaluation of lactose formulations containing salbutamol sulphate. Int J Pharm 423(2):184–194

    Article  CAS  PubMed  Google Scholar 

  • Kato E et al (2018) Incidence and predictive factors of lung cancer in patients with idiopathic pulmonary fibrosis. ERJ Open Res 4(1):00111–02016

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim J et al (2020) The effect of air pollutants on airway innate immune cells in patients with asthma. Allergy 75(9):2372–2376

    Article  PubMed  Google Scholar 

  • Kondo T et al (2019) Pulmonary hypertension: diagnosis, management, and treatment. Nagoya J Med Sci 81(1):19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuo J-HS, Hwang R (2010) Preparation of DNA dry powder for non-viral gene delivery by spray-freeze drying: effect of protective agents (polyethyleneimine and sugars) on the stability of DNA. J Pharm Pharmacol 56(1):27–33

    Article  Google Scholar 

  • Kuo C-Y, Rollings RS, Lynch LN (1998) Morphological study of coarse aggregates using image analysis. J Mater Civ Eng 10(3):135–142

    Article  Google Scholar 

  • Lam XM, Duenas ET, Cleland JL (2001) Encapsulation and stabilization of nerve growth factor into poly(lactic-co-glycolic) acid microspheres. J Pharm Sci 90(9):1356–1365

    Article  CAS  PubMed  Google Scholar 

  • Langford A et al (2018) Drying technologies for biopharmaceutical applications: recent developments and future direction. Dry Technol 36(6):677–684

    Article  CAS  Google Scholar 

  • Larhrib H et al (1999) The use of different grades of lactose as a carrier for aerosolised salbutamol sulphate. Int J Pharm 191(1):1–14

    Article  CAS  PubMed  Google Scholar 

  • Larhrib H et al (2003) Characterisation and deposition studies of engineered lactose crystals with potential for use as a carrier for aerosolised salbutamol sulfate from dry powder inhalers. Eur J Pharm Sci 19(4):211–221

    Article  CAS  PubMed  Google Scholar 

  • Lau M, Young PM, Traini D (2017a) Co-milled API-lactose systems for inhalation therapy: impact of magnesium stearate on physico-chemical stability and aerosolization performance. Drug Dev Ind Pharm 43(6):980–988

    Article  CAS  PubMed  Google Scholar 

  • Lau M, Young PM, Traini D (2017b) A review of co-milling techniques for the production of high dose dry powder inhaler formulation. Drug Dev Ind Pharm 43(8):1229–1238

    Article  CAS  PubMed  Google Scholar 

  • Leuenberger H (2002) Spray freeze-drying—the process of choice for low water soluble drugs? J Nanopart Res 4(1):111–119

    Article  CAS  Google Scholar 

  • Leung SS et al (2016) Production of inhalation phage powders using spray freeze drying and spray drying techniques for treatment of respiratory infections. Pharm Res 33(6):1486–1496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Vogt FG, Hayes D Jr, Mansour HM (2014) Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry powder inhalers. J Aerosol Med Pulmon Drug Deliv 27(2):81–93

    Article  Google Scholar 

  • Li L et al (2016) L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders. Eur J Pharm Biopharm 102:132–141

    Article  CAS  PubMed  Google Scholar 

  • Li L et al (2017) Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation. Int J Pharm 530(1–2):30–39

    Article  CAS  PubMed  ADS  Google Scholar 

  • Lin YW et al (2015) Powder production and particle engineering for dry powder inhaler formulations. Curr Pharm Des 21(27):3902–3916

    Article  CAS  PubMed  Google Scholar 

  • Lin L et al (2017) Development of fine solid-crystal suspension with enhanced solubility, stability, and aerosolization performance for dry powder inhalation. Int J Pharm 533(1):84–92

    Article  CAS  PubMed  Google Scholar 

  • Liu Q et al (2020) Physicochemical properties affecting the fate of nanoparticles in pulmonary drug delivery. Drug Discov Today 25(1):150–159

    Article  CAS  PubMed  Google Scholar 

  • Lozano R et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2095–2128

    Article  PubMed  PubMed Central  Google Scholar 

  • Maa Y-FN, Nguyen P-A (2001) Method of spray freeze drying proteins for pharmaceutical administration. U.S. Patent, Editor. US

  • Maa YF, Prestrelski SJ (2000a) Biopharmaceutical powders: particle formation and formulation considerations. Curr Pharm Biotechnol 1(3):283–302

    Article  CAS  PubMed  Google Scholar 

  • Maa Y-F et al (1999) Protein inhalation powders: spray drying vs spray freeze drying. Pharm Res 16(2):249–254

    Article  CAS  PubMed  Google Scholar 

  • Maas SG et al (2011) The impact of spray drying outlet temperature on the particle morphology of mannitol. Powder Technol 213(1):27–35

    Article  CAS  Google Scholar 

  • Machiste EO et al (1995) Characterization of carbamazepine in systems containing a dissolution rate enhancer. Int J Pharm 126(1):65–72

    Article  CAS  Google Scholar 

  • Maniruzzaman M et al (2012) A review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm 2012:436763

    PubMed  PubMed Central  Google Scholar 

  • Mansour HM, Xu Z, Hickey AJ (2010) Dry powder aerosols generated by standardized entrainment tubes from alternative sugar blends: 3. Trehalose dihydrate and D-mannitol carriers. J Pharm Sci 99(8):3430–3441

    Article  CAS  PubMed  Google Scholar 

  • Martinez L et al (2008) Tuberculosis and air travel: WHO guidance in the era of drug-resistant TB. Travel Med Infect Dis 6(4):177–181

    Article  PubMed  Google Scholar 

  • Martonen TB, Katz IM (1993) Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters. Pharm Res 10(6):871–878

    Article  CAS  PubMed  Google Scholar 

  • Matson DW et al (1987) Rapid expansion of supercritical fluid solutions: solute formation of powders, thin films, and fibers. Ind Eng Chem Res 26(11):2298–2306

    Article  CAS  Google Scholar 

  • McCorry LK (2008) Essentials of human physiology for pharmacy. CRC Press, Boca Raton

    Google Scholar 

  • Moon C et al (2019) Enhanced aerosolization of high potency nanoaggregates of voriconazole by dry powder inhalation. Mol Pharm 16(5):1799–1812

    Article  CAS  PubMed  Google Scholar 

  • Morris AS et al (2017) Cationic CaMKII inhibiting nanoparticles prevent allergic asthma. Mol Pharm 14(6):2166–2175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mossman BT, Gualtieri AF (2020) Lung cancer: mechanisms of carcinogenesis by asbestos. Occupational cancers. Springer, Berlin, pp 239–256

    Chapter  Google Scholar 

  • Muralidharan P et al (2020) Advanced design and development of nanoparticle/microparticle dual-drug combination lactose carrier-free dry powder inhalation aerosols. RSC Adv 10(68):41846–41856

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Newman SP (1985) Aerosol deposition considerations in inhalation therapy. Chest 88(2):152S-S160

    Article  CAS  PubMed  Google Scholar 

  • O’Donnell KP, Smyth HD (2011) Macro-and microstructure of the airways for drug delivery. In: Smyth H, Hickey A (eds) Controlled pulmonary drug delivery. Advances in delivery science and technology. Springer, New York, pp 1–19

    Google Scholar 

  • Ogienko AG et al (2017) Large porous particles for respiratory drug delivery. Glycine-based formulations. Eur J Pharm Sci 110:148–156

    Article  CAS  PubMed  Google Scholar 

  • Olafsdottir TA et al (2020) Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis. Nat Commun 11(1):393

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Organization WH (2014) Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization

  • Organization WH (2017) Guidelines for treatment of drug-susceptible tuberculosis and patient care

  • Otake H, Okuda T, Okamoto H (2016) Development of spray-freeze-dried powders for inhalation with high inhalation performance and antihygroscopic property. Chem Pharm Bull (tokyo) 64(3):239–245

    Article  CAS  PubMed  Google Scholar 

  • Pacifici G et al (1988) Tissue distribution of drug-metabolizing enzymes in humans. Xenobiotica 18(7):849–856

    Article  CAS  PubMed  Google Scholar 

  • Pakhale S, Mulpuru S, Boyd M (2011) Optimal management of severe/refractory asthma. Clin Med Insights Circ Respir Pulmon Med 5:37–47

    CAS  Google Scholar 

  • Papi A et al (2018) Seminar asthma. Lancet 391:783–800

    Article  PubMed  Google Scholar 

  • Patel RP (2009) Spray drying technology: an overview. Indian J Sci Technol 2(10):44–47

    Article  CAS  Google Scholar 

  • Patel B, Gupta N, Ahsan F (2015) Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome. Eur J Pharm Biopharm 89:163–174

    Article  CAS  PubMed  Google Scholar 

  • Paudel A, Van den Mooter G (2012) Influence of solvent composition on the miscibility and physical stability of naproxen/PVP K 25 solid dispersions prepared by cosolvent spray-drying. Pharm Res 29(1):251–270

    Article  CAS  PubMed  Google Scholar 

  • Penttinen P et al (2001) Ultrafine particles in urban air and respiratory health among adult asthmatics. Eur Respir J 17(3):428–435

    Article  CAS  PubMed  Google Scholar 

  • Pilcer G, Wauthoz N, Amighi K (2012) Lactose characteristics and the generation of the aerosol. Adv Drug Deliv Rev 64:233–256

    Article  CAS  PubMed  Google Scholar 

  • Rabe KF et al (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176(6):532–555

    Article  PubMed  Google Scholar 

  • Raghu G et al (2016) Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18–64 years old. Eur Respir J 48(1):179–186

    Article  PubMed  Google Scholar 

  • Raghu G et al (2018) Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 198(5):e44–e68

    Article  PubMed  Google Scholar 

  • Rahimpour Y, Kouhsoltani M, Hamishehkar H (2014) Alternative carriers in dry powder inhaler formulations. Drug Discov Today 19(5):618–626

    Article  PubMed  Google Scholar 

  • Rang HP, Dale MM, Ritter JM, Flower RJ (2007) Rang and Dale’s pharmacology, 6th edn. Elsevier Churchill Livingstone, Edinburgh

    Google Scholar 

  • Rattes ALR, Oliveira WP (2007) Spray drying conditions and encapsulating composition effects on formation and properties of sodium diclofenac microparticles. Powder Technol 171(1):7–14

    Article  CAS  Google Scholar 

  • Rehman M et al (2004) Optimisation of powders for pulmonary delivery using supercritical fluid technology. Eur J Pharm Sci 22(1):1–17

    Article  CAS  PubMed  ADS  Google Scholar 

  • Rey L, May JC (2004) Freeze-drying/lyophilization of pharmaceutical and biological products, revised and expanded, vol 2. CRC Press, Boca Raton

    Book  Google Scholar 

  • Richeldi L, Collard HR, Jones MG (2017) Idiopathic pulmonary fibrosis. Lancet 389(10082):1941–1952

    Article  PubMed  Google Scholar 

  • Rogers TL, Johnston KP, Williams RO 3rd (2001) Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies. Drug Dev Ind Pharm 27(10):1003–1015

    Article  CAS  PubMed  Google Scholar 

  • Rogers TL et al (2003) Enhanced aqueous dissolution of a poorly water soluble drug by novel particle engineering technology: spray-freezing into liquid with atmospheric freeze-drying. Pharm Res 20(3):485–493

    Article  CAS  PubMed  ADS  Google Scholar 

  • Rose-Jones LJ, McLaughlin VV (2015) Pulmonary hypertension: types and treatments. Curr Cardiol Rev 11(1):73–79

    Article  PubMed  PubMed Central  Google Scholar 

  • Saha T et al (2022) Inhaled therapy for COVID-19: considerations of drugs, formulations and devices. Int J Pharm 624:122042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahakijpijarn S et al (2020) Using thin-film freezing to minimize excipients in inhalable tacrolimus dry powder formulations. Int J Pharm 586:119490

    Article  CAS  PubMed  Google Scholar 

  • Saleem IY, Smyth HDC (2010) Micronization of a soft material: air-jet and micro-ball milling. AAPS PharmSciTech 11(4):1642–1649

    Article  PubMed  PubMed Central  Google Scholar 

  • Saleem I, Petkar K, Somavarapu S (2017) Chapter nineteen—rationale for pulmonary vaccine delivery: formulation and device considerations. In: Skwarczynski M, Toth I (eds) Micro and nanotechnology in vaccine development. William Andrew Publishing, Sawston, pp 357–371

    Chapter  Google Scholar 

  • Salvi SS, Barnes PJ (2009) Chronic obstructive pulmonary disease in non-smokers. Lancet 374(9691):733–743

    Article  PubMed  Google Scholar 

  • Schatz M, Rosenwasser L (2014) The allergic asthma phenotype. J Allergy Clin Immunol Pract 2(6):645–648

    Article  PubMed  Google Scholar 

  • Sellers SP et al (2001) Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO(2)-assisted aerosolization. J Pharm Sci 90(6):785–797

    Article  CAS  PubMed  Google Scholar 

  • Shetty N et al (2018) Influence of excipients on physical and aerosolization stability of spray dried high-dose powder formulations for inhalation. Int J Pharm 544(1):222–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoyele SA, Cawthorne S (2006) Particle engineering techniques for inhaled biopharmaceuticals. Adv Drug Deliv Rev 58(9–10):1009–1029

    Article  CAS  PubMed  Google Scholar 

  • Smola M, Vandamme T, Sokolowski A (2008) Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non-respiratory diseases. Int J Nanomed 3(1):1–19

    CAS  Google Scholar 

  • Somers GI et al (2007) A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos 35(10):1797–1805

    Article  CAS  PubMed  Google Scholar 

  • Sood A et al (2018) ERS/ATS workshop report on respiratory health effects of household air pollution. Eur Respir J 51(1):1700698

    Article  PubMed  PubMed Central  Google Scholar 

  • Sözener ZC et al (2020) Environmental factors in epithelial barrier dysfunction. J Allergy Clin Immunol 145(6):1517–1528

    Article  Google Scholar 

  • Spagnolo P et al (2012) Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges. Multidiscip Respir Med 7:1–10

    Article  Google Scholar 

  • Steckel H, Müller BW (1998) Metered-dose inhaler formulation of fluticasone-17-propionate micronized with supercritical carbon dioxide using the alternative propellant HFA-227. Int J Pharm 173(1):25–33

    Article  CAS  Google Scholar 

  • Sun D (2020) Remdesivir for Treatment of COVID-19: combination of pulmonary and IV administration may offer additional benefit. AAPS J 22(4):77

    Article  CAS  PubMed  Google Scholar 

  • Taherali F, Varum F, Basit AW (2018) A slippery slope: on the origin, role and physiology of mucus. Adv Drug Deliv Rev 124:16–33

    Article  CAS  PubMed  Google Scholar 

  • Tang P, Chan HK, Raper JA (2004) Prediction of aerodynamic diameter of particles with rough surfaces. Powder Technol 147(1):64–78

    Article  CAS  Google Scholar 

  • Telko MJ, Hickey AJ (2005) Dry powder inhaler formulation. Respir Care 50(9):1209–1227

    PubMed  Google Scholar 

  • Tena AF, Clarà PC (2012) Deposition of inhaled particles in the lungs. Arch Bronconeumol (english Edn) 48(7):240–246

    Article  Google Scholar 

  • Thiering R et al (2000) Solvent effects on the controlled dense gas precipitation of model proteins. J Chem Technol Biotechnol 75(1):42–53

    Article  CAS  Google Scholar 

  • Thum T et al (2006) Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and non-smokers. Environ Health Perspect 114(11):1655–1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tzouvelekis A, Bonella F, Spagnolo P (2015) Update on therapeutic management of idiopathic pulmonary fibrosis. Therap Clin Risk Manag:359–370

  • Van Campen L, Amidon GL, Zografi G (1983) Moisture sorption kinetics for water-soluble substances I: theoretical considerations of heat transport control. J Pharm Sci 72(12):1381–1388

    Article  PubMed  Google Scholar 

  • Vehring R (2008) Pharmaceutical particle engineering via spray drying. Pharm Res 25(5):999–1022

    Article  CAS  PubMed  Google Scholar 

  • Velaga SP, Carlfors J (2005) Supercritical fluids processing of recombinant human growth hormone. Drug Dev Ind Pharm 31(2):135–149

    Article  CAS  Google Scholar 

  • Villemagne B et al (2012) Tuberculosis: the drug development pipeline at a glance. Eur J Med Chem 51:1–16

    Article  CAS  PubMed  Google Scholar 

  • Visser J (1989) Van der Waals and other cohesive forces affecting powder fluidization. Powder Technol 58(1):1–10

    Article  MathSciNet  CAS  Google Scholar 

  • Walters RH et al (2014) Next generation drying technologies for pharmaceutical applications. J Pharm Sci 103(9):2673–2695

    Article  CAS  PubMed  Google Scholar 

  • Wang C et al (2006) Combination of adsorption by porous CaCO3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery. Int J Pharm 308(1):160–167

    Article  CAS  PubMed  Google Scholar 

  • Wang Y et al (2009) Polyelectrolyte mediated formation of hydroxyapatite microspheres of controlled size and hierarchical structure. J Colloid Interface Sci 339(1):69–77

    Article  CAS  PubMed  ADS  Google Scholar 

  • Ward GH, Schultz RK (1995) Process-induced crystallinity changes in albuterol sulfate and its effect on powder physical stability. Pharm Res 12:773–779

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (1963) Morphometry of the human lung. Springer and Academic Press, New York

    Book  Google Scholar 

  • W.h. Organization, WHO (ed) (2023) Therapeutics and COVID-19: living guideline, 13 January 2023. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2023.1

  • WHO Coronavirus (COVID-19) Dashboard (2023) https://covid19.who.int/

  • World Health Organization (2016) Factsheet—the shorter MDR-TB regimen

  • World Health Organization (ed) (2017) Chronic respiratory diseases. http://www.who.int/respiratory/en

  • World Health Organization (ed) (2019) Chronic obstructive pulmonary disease (COPD). http://www.who.int/respiratory/copd/en/

  • Wilson EM, Luft JC, DeSimone JM (2018) Formulation of high-performance dry powder aerosols for pulmonary protein delivery. Pharm Res 35(10):195

    Article  PubMed  Google Scholar 

  • Wynn TA (2011) Integrating mechanisms of pulmonary fibrosis. J Exp Med 208(7):1339–1350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J et al (2012) Rendering protein-based particles transiently insoluble for therapeutic applications. J Am Chem Soc 134(21):8774–8777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J et al (2013) Future of the particle replication in nonwetting templates (PRINT) technology. Angew Chem (international Ed. in English) 52(26):6580–6589

    Article  CAS  Google Scholar 

  • Yeo SD et al (1993) Formation of microparticulate protein powder using a supercritical fluid antisolvent. Biotechnol Bioeng 41(3):341–346

    Article  CAS  PubMed  Google Scholar 

  • Yu J et al (2004a) Morphological control of calcium oxalate particles in the presence of poly-(styrene-alt-maleic acid). J Solid State Chem 177(10):3368–3374

    Article  CAS  ADS  Google Scholar 

  • Yu J et al (2004b) Facile preparation of calcium carbonate particles with unusual morphologies by precipitation reaction. J Cryst Growth 261(4):566–570

    Article  CAS  ADS  Google Scholar 

  • Yu J et al (2018) Protective effect of sodium stearate on the moisture-induced deterioration of hygroscopic spray-dried powders. Int J Pharm 541(1–2):11–18

    CAS  PubMed  Google Scholar 

  • Zeng XM et al (2000) The influence of carrier morphology on drug delivery by dry powder inhalers. Int J Pharm 200(1):93–106

    Article  CAS  PubMed  Google Scholar 

  • Zeng X, Martin G, Marriott C (2000) Particulate interactions in dry powder formulation for inhalation. CRC Press, Boca Raton

    Book  Google Scholar 

  • Zhou QT et al (2010) Understanding the influence of powder flowability, fluidization and de-agglomeration characteristics on the aerosolization of pharmaceutical model powders. Eur J Pharm Sci 40(5):412–421

    Article  CAS  PubMed  Google Scholar 

  • Zhou QT et al (2013) Effect of surface coating with magnesium stearate via mechanical dry powder coating approach on the aerosol performance of micronized drug powders from dry powder inhalers. AAPS PharmSciTech 14(1):38–44

    Article  PubMed  Google Scholar 

  • Zhou Q et al (2014) Synergistic antibiotic combination powders of colistin and rifampicin provide high aerosolization efficiency and moisture protection. AAPS J 16(1):37–47

    Article  PubMed  Google Scholar 

  • Zhou QT et al (2016) How much surface coating of hydrophobic azithromycin is sufficient to prevent moisture-induced decrease in aerosolisation of hygroscopic amorphous colistin powder? AAPS J 18(5):1213–1224

    Article  CAS  PubMed  Google Scholar 

  • Zografi G (1988) States of water associated with solids. Drug Dev Ind Pharm 14(14):1905–1926

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by National Research Foundation of Korea Grants funded by the Korean government (NRF-2021R1A2C4002746 and 2017R1A5A2015541). And also, this research was also supported by “Regional Innovation Strategy (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2021RIS-001). We would like to thank Editage (http://www.editage.co.kr) for English language editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chun-Woong Park.

Ethics declarations

Conflict of interest

All authors (Min-Seok Yang, Ji-Hyun Kang, Dong-Wook Kim, and Chun-Woong Park) declare that they have no conflict of interest.

Research involving human and animal rights

This article does not contain any studies with human and animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, MS., Kang, JH., Kim, DW. et al. Recent developments in dry powder inhalation (DPI) formulations for lung-targeted drug delivery. J. Pharm. Investig. 54, 113–130 (2024). https://doi.org/10.1007/s40005-023-00635-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-023-00635-w

Keywords

Navigation