Abstract
Inhalational route for drug delivery and desired effects has been known since centuries. This lung-targeted therapy has benefited asthmatics and those with chronic respiratory problems. The technique has evolved greatly from crude pots and pipes to modern sophisticated drug-dispensing devices. This mode is effective, rapid and safe. Its outcome, however, is majorly determined by drug formulation, device structure and patient's coordinating skill. In spite of great advances in this field, more efforts are required to meet the unmet needs. This noninvasive mode is being increasingly studied for transfer of drugs for systemic action with promising results. The present article is an attempt to capture the recent development and progress in this field and review relevant newer patents.
Papers of special note have been highlighted as: •• of considerable interest
References
- 1 . Pulmonary drug delivery: an historical overview. In: Controlled Pulmonary Drug Delivery. Smyth HDC, Hickey AJ (Eds). Springer, NY, USA, 51–73 (2011).
- 2 . Lung anatomy and physiology and their implications for pulmonary drug delivery. In: Pulmonary Drug Delivery: Advances and Challenges. Nokhodchi A, Martin GP (Eds). John Wiley and Sons, Inc., West Sussex, UK, 1 (2015).
- 3 . Inhalation drug delivery devices: technology update. Med. Devices (Auckl.) 8, 131–139 (2015). •• A concise, comprehensive review about the various pulmonary drug delivery devices.
- 4 . Recent advances in controlled pulmonary drug delivery. Drug Discov. Today 20(3), 380–389 (2015). •• A review of the sustained release preparations for pulmonary use.
- 5 . Influence of particle size on regional lung deposition – what evidence is there? Int. J. Pharm. 406(1–2), 1–10 (2011).
- 6 . Aerosol deposition in the human lung in reduced gravity. J. Aerosol Pulm. Drug Deliv. 27(3), 170–177 (2014).
- 7 . Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers. J. Aerosol Med. 11(4), 231–245 (2009).
- 8 . Factors influencing aerodynamic particle size distribution of suspension pressurized metered dose inhalers. AAPS PharmSciTech. 16(1), 192–201 (2015).
- 9 . Transport mechanisms at the pulmonary mucosa: implications for drug delivery. Expert Opin. Drug Deliv. 13(5), 667–690 (2016).
- 10 . Pulmonary drug delivery system: a novel approach for drug delivery. Curr. Drug Ther. 6, 137–151 (2011).
- 11 . The adaptive aerosol delivery (AAD) technology: past, present, and future. J. Aerosol Med. Pulm. Drug Deliv. 23(S1), S1–S10 (2010). •• A comprehensive review on the newer techniques in drug delivery via lungs.
- 12 Activaero Gmbh: US20100092397 (2010).
- 13 . In vitro characterization of the I-Neb adaptive aerosol delivery (AAD) system. J. Aerosol Med. Pulm. Drug Deliv. 23(Suppl. 1), S11–S20 (2010).
- 14 . Intelligent nebulizers in the age of the internet: the I-Neb adaptive aerosol delivery (AAD) system. J. Aerosol Med. Pulm. Drug Deliv. 23(Suppl. 1), iii–v (2010).
- 15 . The function and performance of aqueous aerosol devices for inhalation therapy. J. Pharm. Pharmacol. 68(5), 556–578 (2016).
- 16 . Emerging inhalation aerosol devices and strategies: where are we headed? Adv. Drug Deliv. Rev. 75, 3–17 (2014).
- 17 Aerogen, Inc.: US20090134235 (2009).
- 18 In vitro performance testing of the novel MedSpray® wet aerosol inhaler based on the principle of Rayleigh break-up. Pharm. Res. 25(5), 1186–1192 (2008).
- 19 . HDA – a new pulmonary drug delivery platform can provide for more efficient and safer delivery. On Drug Delivery 1, 8–10 (2011).
- 20 . Advances in device and formulation technologies for pulmonary drug delivery. AAPS Pharm. Sci. Tech. 15(4), 882–897 (2014).
- 21 . The evolution of spacers and valved holding chambers. J. Aerosol Med. Pulm. Drug Deliv. 27(Suppl. 1), S4–S23 (2014).
- 22 . Using electronic monitoring devices to measure inhaler adherence: a practical guide for clinicians. J. Allergy Clin. Immunol. Pract. 3(3), 335–349 (2015). •• An excellent review about the various compliance monitoring devices available and how to use and ready them.
- 23 . Integration of dose counters in pressurized metered-dose inhalers for patients with asthma and chronic obstructive pulmonary disease: a review of evidence. Expert Opin. Drug Deliv. 12(8), 1301–1310 (2015).
- 24 . Advances in metered dose inhaler technology: formulation development. AAPS PharmSciTech. 15(2), 434–455 (2014). •• An excellent review on pressurized metered-dose inhaler and its formulations.
- 25 . Dry powder inhalation: past, present and future. Exp. Opin. Drug Deliv. 14(4), 499–512 (2017).
- 26 Alexza Pharmaceuticals: US7581540 (2009).
- 27 3M Innovative Properties Company: EP1996173 (2008).
- 28 . New inhaler devices – the good, the bad and the ugly. Respiration 88, 3–15 (2014).
- 29 . The Respimat soft mist inhaler, a novel inhaled drug delivery device. Conn. Med. 80(6), 359–364 (2016).
- 30 . Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics 8(1), 6 (2016).
- 31 Ventaira Pharmaceuticals, Inc.: US20080308095 (2008).
- 32 Tanaka Kikinzoku Kogyo KK: EP2644282 (2013).
- 33 Novartis Ag: US8616195 (2013).
- 34 Island Breeze systems Co., Inc.: WO2016187156 (2016).
- 35 . Recent patents in pressurised metered dose inhalers. Recent Pat. Drug Deliv. Formul. 6(1), 31–44 (2012).
- 36 3M Innovative Properties Company: US20170021117 (2017).
- 37 Map Pharmaceuticals, Inc.: US20170007786 (2017).
- 38 Koninklijke Philips Electronics NV: US8960189 (2015).
- 39 Virginia Commonwealth University: WO2013169473 (2013).
- 40 Respira Therapeutics, Inc.: US8651104 (2014).
- 41 Vectura Delivery Devices Limited, Boehringer Ingelheim Gmbh: US20140373839 (2014).
- 42 Oriel Therapeutics, Inc.: US9027551 (2015).
- 43 . The cyclops for pulmonary delivery of aminoglycosides; a new member of the Twincer™ family. Eur. J. Pharm. Biopharm. 90, 8–15 (2015).
- 44 Aespira Limited: US20130032145 (2013).
- 45 Hovione International Ltd: US8677992 (2014).
- 46 MannKind Corporation: US9192675 (2015).
- 47 MannKind Corporation: US20160228659 (2016).
- 48 STC UNM: US20120234322 (2012).
- 49 US20110253141 (2011).
- 50 Pharmaxis Ltd.: US20140174441 (2014).
- 51 Inhaleness BV: WO2010052323 (2010).
- 52 Reciprocal Labs Corporation: USD757926 (2016).
- 53 FSC Laboratories, Inc.: US20170021118 (2017).
- 54 . US20160367770 (2016).
- 55 . Fluticasone propionate/formoterol breath-triggered inhaler: ease-of-use and patient preference. Eur. Resp. J. 48, PA4109 (2016).
- 56 Adamis Pharmaceuticals Corporation: US20150217065 (2015).
- 57 Multi-breath dry powder inhaler for delivery of cohesive powders in the treatment of bronchiectasis. Drug Dev. Ind. Pharm. 41(5), 859–865 (2015).
- 58 Pharmaxis Ltd.: US20140137865 (2014).
- 59 . Dynamics of aerosol size during inhalation: hygroscopic growth of commercial nebulizer formulations. Int. J. Pharm. 463(1), 50–61 (2014).
- 60 . Generation of liposome aerosols with the Aeroneb Pro and the AeroProbe nebulizers. J. Liposome Res. 20(1), 55–61 (2010).
- 61 Clinical experimentation with aerosol antibiotics: current and future methods of administration. Drug Des. Devel. Ther. 7, 1115–1134 (2013).
- 62 Mexichem Amanco Holdings S.A. De C.V.: US20170027867 (2017).
- 63 Pipeline: APC-1000 – HFA inhaled oral steroid. www.adamispharmaceuticals.com/pipeline/apc-1000/.
- 64 Boehringer-Ingelheim Pvt Ltd: US7914770 (2011).
- 65 Intech Biopharm Ltd: US9241904 (2016).
- 66 Cardiff Scintigraphics Limited: US20160354564 (2016).
- 67 Sunovion Pharmaceuticals, Inc.: US20160368858 (2016).
- 68 Jagotec Ag: US20160310452 (2016).
- 69 . Insoluble drug delivery strategies: review of recent advances and business prospects. Int. J. Pharm. 5(5), 442–453 (2015).
- 70 . The PulmoSphere platform for pulmonary drug delivery. Ther. Deliv. 5(3), 277–295 (2014).
- 71 . Cosuspensions of microcrystals and engineered microparticles for uniform and efficient delivery of respiratory therapeutics from pressurized metered dose inhalers. Langmuir 28(42), 15015–15023 (2012).
- 72 Pearl Therapeutics, Inc.: US20170000725 (2017).
- 73 A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD. Resp. Med. 108(9), 327–335 (2014).
- 74 Adamis Pharmaceuticals Corporation: US20150190593 (2015).
- 75 Adamis Pharmaceuticals Corporation: US9433576 (2016).
- 76 Rainer Schlichthaar: US20110190245 (2011).
- 77 . Co-spray-dried mannitol-cisprofloxacin dry powder inhaler formulation for cystic fibrosis and chronic obstructive pulmonary disease. Eur. J. Pharm. Sci. 40(3), 239–247 (2010).
- 78 Alkermes Pharma: US8097282 (2012).
- 79 Jagotec Ag: US8877251 (2014).
- 80 Vectura Limited: WO2014106727 (2014).
- 81 Schering Corporation: WO2010124198 (2010).
- 82 MannKind Corporation: US8551528 (2013).
- 83 . Pharmacokinetic characterization of the novel pulmonary delivery excipient fumaryl diketopiperazine. J. Diabetes Sci. Technol. 4(5), 1164–1173 (2010).
- 84 MannKind Corporation: US7648960 (2010).
- 85 . Formation of protein nano-matrix particles with controlled surface architecture for respiratory drug delivery. Pharm. Res. 28, 788–796 (2011).
- 86 Insmed Incorporated: US9549939 (2017).
- 87 Aradigm Corporation: US9545401 (2017).
- 88 . Development of an inhaled dry powder formulation of tobramycin using pulmosphere technology. J. Aerosol Med. Pulm. Drug Deliv. 24(4), 175–182 (2011).
- 89 Novartis Ag: US20140302147 (2014).
- 90 Università Degli Studi “Magna Graecia” Catanzaro, Università Degli Studi Di Roma “La Sapienza”: US20120288540 (2012).
- 91 . Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J. Control. Release 185, 22–36 (2014).
- 92 Hovione International Ltd: US20160346206 (2016).
- 93 . Stability and purity of a bacteriophage cocktail preparation for nebulizer delivery. Lett. Appl. Microbiol. 58, 118–122 (2014).
- 94 . In vitro lung delivery of bacteriophages KS4-M and ΦKZ using dry powder inhalers for treatment of Burkhloderia cepacia complex and Pseudomonas aeruginosa infections in cystic fibrosis. J. Appl. Microbiol. 110, 106–117 (2010).
- 95 Bayer Healthcare Ag: US20120247462 (2012).
- 96 . Aerosolized antibiotics: do they add to the treatment of pneumonia? Curr. Opin. Infect. Dis. 26(6), 538–544 (2013).
- 97 . In vitro efficiency of the Amikacin inhale system, a novel integrated drug-device delivery system, poster A384. Presented at: 33rd International Symposium on Intensive Care and Emergency Medicine. Brussels, Belgium, 19–22 March 2013.
- 98 Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis. J. Pharm. Pharmacol. 65(9), 1302–1311 (2013).
- 99 . Dry powder inhalable formulations for anti-tubercular therapy. Adv. Drug Deliv. Rev. 102, 83–101 (2016).
- 100 In vitro evaluation of novel inhalable dry powders consisting of thioridazine and rifapentine for rapid tuberculosis treatment. Eur. J. Pharm. Biopharm. 107, 205–214 (2016).
- 101 . Novel drug delivery systems: desired feats for tuberculosis. J. Adv. Pharm. Technol. Res. 1(2), 145–163 (2010).
- 102 . Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: a new approach to therapy of drug-resistant tuberculosis. Antimicrob. Agents Chemother. 57(6), 2613–2619 (2013).
- 103 Effects of surface composition on the aerosolisation and dissolution of inhaled antibiotic combination powders consisting of colistin and rifampicin. AAPS J. 18(2), 372–384 (2016).
- 104 . Aerosolized delivery of antifungal agents. Curr. Fungal Infect. Rep. 4(2), 96–102 (2010).
- 105 Aradigm Corporation: US20150110855 (2015).
- 106 Ablynx NV, Vectura Gmbh: WO2016055656 (2016).
- 107 Pulmatrix, Inc.: US9433576 (2017).
- 108 Topigen Pharmaceuticals, Inc.: US20120065249 (2012).
- 109 TPI ASM8 reduces eosinophil progenitors in sputum after allergen challenge. Clin. Exp. Allergy 41(12), 1740–1746 (2011).
- 110 . Attacks on asthma. Nat. Biotechnol. 29(10), 860–863 (2011).
- 111 . Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb Pro: formulation aspects and nanoparticle stability to nebulization. Int. J. Pharm. 422(1–2), 398–408 (2012).
- 112 Hsin-Yung Lin: US9339456 (2016).
- 113 . Efficacy of aerosolized celecoxib encapsulated nanostructured lipid carrier in non-small cell lung cancer in combination with docetaxel. Pharm. Res. 30(5), 1435–1446 (2013).
- 114 . Development of aqueous dispersions of coenzyme Q10 for pulmonary delivery and the dynamics of active vibrating-mesh aerosolization. Int. J. Pharm. 514(2), 407–419 (2016).
- 115 Development of chitosan-based dry powder inhalation system of cisplatin for lung cancer. Indian J. Pharm. Sci. 74(6), 521–526 (2012).
- 116 . Inhaled nicotine replacement therapy. Asian J. Pharm. Sci. 10(6), 472–480 (2015).
- 117 Inhaled fentanyl aerosol in healthy volunteers: pharmacokinetics and pharmacodynamics. Anesth. Analg. 115(5), 1071–1077 (2012).
- 118 . Inhaled proteins and peptides in: advances in pulmonary drug delivery. Kwok PCL, Chan H-K (Eds). CRC Press, FL, USA, 1–22 (2016).
- 119 Otitopic, Inc.: US20160022705 (2016).
- 120 Aarhus Universitet: US20110033547 (2011).
- 121 . SiRNA delivery to the lung: what's new? Adv. Drug. Del. Rev. 30, 112–128 (2014).
- 122 . In vitro reporter gene transfection via plasmid DNA delivered by metered dose inhaler. J. Pharm. Sci. 99(7), 3089–3099 (2010).
- 123 . Nasal and pulmonary vaccine delivery using particulate carriers. Expert Opin. Drug Deliv. 12(6), 993–1008 (2015).
- 124 MannKind Corporation, Technovax, Inc.: US20150283069 (2015).
- 125 . Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. PNAS 109(4), 1080–1085 (2012).
- 126 MVDP author group. Safety and immunogenicity of dry powder measles vaccine administered by inhalation: a randomized controlled Phase I clinical trial. Vaccine 32(50), 6791–6787 (2014).
- 127 Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren. Bull. World Health Organ. 80, 806–812 (2002).
- 128 . Successful seroresponses to measles and rubella following aerosolized Triviraten vaccine, but poor response to aerosolized mumps (Rubini) component: comparisons with injected MMR. Vaccine 28, 692–698 (2010).
- 129 The United States of America as represented by The Secretary of The Department of Health and Human Services: US8481055 (2013).
- 130 . Pharmaceutical aerosols for the treatment and prevention of tuberculosis. Front. Cell Infect. Microbiol. 2, 118 (2012).
- 131 . Aerosol vaccines for tuberculosis: a fine line between protection and pathology. Tuberculosis (Edinb.) 91(1), 2–5 (2011).