Development of dry powder inhaler formulations for drug delivery systems

Yagmur Akdag

Development of dry powder inhaler formulations for drug delivery systems

Abstract

Oral or parenteral administration of drugs to treat lung diseases is met with several challenges, including delivery of the active substance in insufficient amounts, inability to produce the desired effect at the target region, and severe systemic side effects. The best solution to this problem is the pulmonary administration of drugs. Although several formulations for administering inhaled medications such as nebulizers and metered-dose inhalers are available, dry powder inhalers (DPIs) are particularly advantageous owing to their ability to administer a high amount of active ingredient in a short time and higher stability than that of aqueous formulations. Similar to all inhaler formulations, one of the major problems encountered in DPIs is the inability of the active substance to reach the peripheral lungs in sufficient quantity. Moreover, reproducible results are difficult to obtain due to different inhalation capacities among individuals. This review provides the readers with a general perspective on different approaches used in developing various DPIs. Moreover, the review discusses the aerodynamic parameters of these formulations. DPIs developed with novel manufacturing methods are safe with increased therapeutic efficacy, as demonstrated by the results of their in vitro and in vivo safety and efficacy studies. These findings indicate that DPIs could serve as a promising modality for pulmonary drug delivery.

Keywords

References

[1] Maitra A, Kumar V, The lung. In: Kumar V, Abbas AK, Aster JC. (Eds.). Robbins Basic Pathology. Elsevier Health Sciences, Pennsylvania, 2017, pp. 479–539.
[2] Yhee JY, Im J, Nho RS. Advanced therapeutic strategies for chronic lung disease using nanoparticle-based drug delivery. J Clin Med. 2016; 5(9): 82. [CrossRef]
[3] Patil TS, Deshpande AS. Nanostructured lipid carriers-based drug delivery for treating various lung diseases: a state‐of‐the‐art review. Int J Pharm. 2018; 547(1): 209-225. [CrossRef]
[4] da Silva AL, Cruz FF, Rocco PRM, Morales MM. New perspectives in nanotherapeutics for chronic respiratory diseases. Biophys Rev. 2017; 9(5): 793–803. [CrossRef]
[5] Rodrigo GJ. Rapid effects of inhaled corticosteroids in acute asthma. Chest. 2006; 130(5): 1301–1311. [CrossRef]
[6] Erin EM, Zacharasiewicz AS, Nicholson GC, Tan AJ, Neighbour H, Engelstätter R, Hellwig M, Kon OM, Barnes PJ, Hansel TT. Rapid effect of inhaled ciclesonide in asthma. Chest. 2008; 134(4): 740–745. [CrossRef]
[7] Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003; 56(6): 588–599. [CrossRef]
[8] Groneberg DA, Witt C, Wagner U, Chung KF, Fischer A. Fundamentals of pulmonary drug delivery. Respir Med. 2003; 97(4): 382–387. [CrossRef]

[9] Brzoska M, Langer K, Coester C, Loitsch S, Wagner TO, Mallinckrodt C. Incorporation of biodegradable nanoparticles into human airway epithelium cells-in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases. Biochem Biophys Res Commun. 2004; 318(2): 562–570. [CrossRef]
[10] Jansen M, Darby I, Abribat T, Dubreuil P, Ferdinandi ES, Hardy JG. Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. Int J Pharm. 2004; 276(1–2): 75–81. [CrossRef]
[11] Bosquillon C, Préat V, Vanbever R. Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J Control Release. 2004; 96(2): 233–244. [CrossRef]
[12] Bivas-Benita M, van Meijgaarden KE, Franken KLMC, Junginger HE, Borchard G, Ottenhoff TH, Gelu A. Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis. Vaccine. 2004; 22(13–14): 1609–1615. [CrossRef]
[13] Reynolds PN. Delivery of DNA to pulmonary endothelium using adenoviral vectors. Methods Mol Biol. 2004; 246: 69-89. [CrossRef]
[14] Brain JD. Inhalation, deposition, and fate of insulin and other therapeutic proteins. Diabetes Technol Ther. 2007; 9 Suppl 1: S4–S15. [CrossRef]
[15] Okamoto H, Todo H, Iida K, Danjo K. Dry powders for pulmonary delivery of peptides and proteins. Kona. 2002; 20: 71–83. [CrossRef]
[16] Johnson KA. Preparation of peptide and protein powders for inhalation. Adv Drug Deliv Rev. 1997; 26(1): 3–15. [CrossRef]
[17] Iyer R, CW Hsia C, T Nguyen K. Nano-therapeutics for the lung: state-of-the-art and future perspectives. Curr Pharm Des. 2015; 21(36): 5233–5244.
[18] Paranjpe M, Müller-Goymann CC. Nanoparticle-mediated pulmonary drug delivery: a review. Int J Mol Sci. 2014; 15(4): 5852–5873. [CrossRef]
[19] Blau H, Mussaffi H, Mei Zahav M, Prais D, Livne M, Czitron BM, Cohen HA. Microbial contamination of nebulizers in the home treatment of cystic fibrosis. Child Care Hlth Dev. 2007; 33(4): 491–495. [CrossRef]
[20] Cohen HA, Cohen Z, Pomeranz AS, Czitron B, Kahan E. Bacterial contamination of spacer devices used by asthmatic children. J Asthma. 2005; 42(3): 169–172. [CrossRef]
[21] de Vries TW, Rienstra SR, van der Vorm ER. Bacterial contamination of inhalation chambers: results of a pilot study. J Aerosol Med. 2004; 17(4): 354–356. [CrossRef]
[22] Chow AH, Tong HHY, Chattopadhyay P, Shekunov BY. Particle engineering for pulmonary drug delivery. Pharm Res. 2007; 24(3): 411–437. [CrossRef]
[23] Patil-Gadhe A, Kyadarkunte A, Patole M, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance. Eur J Pharm Biopharm. 2014; 88(1): 169–177. [CrossRef]
[24] Timsina MP, Martin GP, Marriott C, Ganderton D, Yianneskis M. Drug delivery to the respiratory tract using dry powder inhalers. Int J Pharm. 1994; 101(1): 1–13. [CrossRef]
[25] Heyder J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc. 2004; 1(4): 315–320. [CrossRef]
[26] Q1A(R2) Stability Testing of New Drug Substances and Products. ICH Harmonised Tripartite Guideline, 2003.
[27] Q1C Stability Testing for New Dosage Forms. ICH Harmonised Tripartite Guideline, 1996.
[28] Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products. ICH Harmonised Tripartite Guideline, 2002.
[29] Q1E Evaluation for Stability Data. ICH Harmonised Tripartite Guideline, 2003.
[30] Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products - Quality Considerations Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), 2018.
[31] Zhang J, Wu L, Chan HK, Watanabe W. Formation, characterization, and fate of inhaled drug nanoparticles. Adv Drug Deliv Rev. 2011; 63(6): 441–455. [CrossRef]
[32] Salama RO, Traini D, Chan HK, Sung A, Ammit AJ, Young PM. Preparation and evaluation of controlled release microparticles for respiratory protein therapy. J Pharm Sci. 2009; 98(8): 2709–2017. [CrossRef]
[33] Roberts RA, Shen T, Allen IC, Hasan W, DeSimone JM, Ting JP. Analysis of the murine immune response to pulmonary delivery of precisely fabricated nano- and microscale particles. PloS One. 2013; 8(4): e62115. [CrossRef]
[34] Dailey LA, Jekel N, Fink L, Gessler T, Schmehl T, Wittmar M, Kissel T, Seeger W. Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung. Toxicol Appl Pharmacol. 2006; 215(1): 100–108. [CrossRef]
[35] Miranda MS, Rodrigues MT, Domingues RMA, Torrado E, Reis RL, Pedrosa J, Gomes ME. Exploring inhalable polymeric dry powders for anti-tuberculosis drug delivery. Mater Sci Eng C. 2018; 93: 1090–1103. [CrossRef]
[36] Tomashefski JF, Cohen AM, Doershuk CF. Long term histopathologic follow-up of bronchial arteries after therapeutic embolization with polyvinyl alcohol (Ivalon) in patients with cystic fibrosis. Hum Pathol. 1988; 19(5): 555–561. [CrossRef]
[37] Hitzman CJ, Elmquist WF, Wattenberg LW, Wiedmann TS. Development of a respirable, sustained release microcarrier for 5-fluorouracil I: in vitro assessment of liposomes, microspheres, and lipid coated nanoparticles. J Pharm Sci. 2006; 95(5): 1114–1126. [CrossRef]
[38] Alipour S, Montaseri H, Tafaghodi M. Preparation and characterization of biodegradable paclitaxel loaded alginate microparticles for pulmonary delivery. Colloids Surf B Biointerfaces. 2010; 81(2): 521–529. [CrossRef]
[39] Fiegel J, Fu J, Hanes J. Poly(ether-anhydride) dry powder aerosols for sustained drug delivery in the lungs. J Control Release. 2004; 96(3): 411–423. [CrossRef]
[40] Sivadas N, Cryan SA. Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs. J Pharm Pharmacol. 2011; 63(3): 369–375. [CrossRef]
[41] Sham JO, Zhang Y, Finlay WH, Roa WH, Lobenberg R. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm. 2004; 269(2): 457–467. [CrossRef]
[42] Andrade F, Fonte P, Costa A, Reis CC, Nunes R, Almeida A, Ferreira D, Oliva M, Sarmento B. Pharmacological and toxicological assessment of innovative self-assembled polymeric micelles as powders for insulin pulmonary delivery. Nanomedicine (Lond). 2016; 11(17): 2305–2317. [CrossRef]
[43] Rezazadeh M, Davatsaz Z, Emami J, Hasanzadeh F, Jahanian-Najafabadi A. Preparation and Characterization of Spray-Dried Inhalable Powders Containing Polymeric Micelles for Pulmonary Delivery of Paclitaxel in Lung Cancer. J Pharm Pharm Sci. 2018; 21(1s): 200-214. [CrossRef]
[44] Farhangi M, Mahboubi A, Kobarfard F, Vatanara A, Mortazavi SA. Optimization of a dry powder inhaler of ciprofloxacin-loaded polymeric nanomicelles by spray drying process. Pharm Dev Technol. 2019; 24(5): 584-592. [CrossRef]
[45] Buttini F, Colombo P, Wenger MPE, Mesquida P, Marriott C, Jones SA. Back to basics: the development of a simple, homogenous, two‐component dry‐powder inhaler formulation for the delivery of budesonide using miscible vinyl polymers. J Pharm Sci. 2008; 97(3): 1257–1267. [CrossRef]
[46] Koushik K, Dhanda DS, Cheruvu NPS, Kompella UB. Pulmonary Delivery of Deslorelin: Large-Porous PLGA Particles and HPβCD Complexes. Pharm Res. 2004; 21(7): 1119–1126. [CrossRef]
[47] Kim I, Byeon HJ, Kim TH, Lee ES, Oh KT, Shin BS, Lee KC, Youn YS. Doxorubicin-loaded highly porous large PLGA microparticles as a sustained-release inhalation system for the treatment of metastatic lung cancer. Biomaterials. 2012; 33(22): 5574-5583. [CrossRef]
[48] Ungaro F, De Rosa G, Miro A, Quaglia F, La Rotonda MI. Cyclodextrins in the production of large porous particles: Development of dry powders for the sustained release of insulin to the lungs. Eur J Pharm Sci. 2006; 28(5): 423–432. [CrossRef]
[49] Elhissi AMA, Taylor KMG. Delivery of liposomes generated from proliposomes using air-jet, ultrasonic, and vibrating-mesh nebulisers. J Drug Deliv Sci Technol. 2005; 15(4): 261–265. [CrossRef]
[50] Song KH, Chung SJ, Shim CK. Preparation and evaluation of proliposomes containing salmon calcitonin. J Control Release. 2002; 84(1–2): 27-37. [CrossRef]
[51] Rojanarat W, Changsan N, Tawithong E, Pinsuwan S, Chan HK, Srichana T. Isoniazid proliposome powders for inhalation-preparation, characterization and cell culture studies. Int J Mol Sci. 2011; 12(7): 4414–4434. [CrossRef]
[52] Patil-Gadhe A, Pokharkar V. Single step spray drying method to develop proliposomes for inhalation: a systematic study based on quality by design approach. Pulm Pharmacol Ther. 2014; 27(2): 197-207. [CrossRef]
[53] Li M, Zhang T, Zhu L, Wang R, Jin Y. Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway. Int J Pharm. 2017; 528(1): 163-171. [CrossRef]
[54] Chennakesavulu S, Mishra A, Sudheer A, Sowmya C, Reddy CS, Bhargav E. Pulmonary delivery of liposomal dry powder inhaler formulation for effective treatment of idiopathic pulmonary fibrosis. Asian J Pharm Sci. 2018; 13(1): 91-100. [CrossRef]
[55] Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm. 2000; 50(1): 161-77. [CrossRef]
[56] Rosière R, Amighi K, Wauthoz N, Dalby R, Byron PR, Peart J, et al., editors. New dry Powders for Inhalation containing Chitosan Derivative-coated Solid Lipid Nanoparticles for Targeted Delivery to Lung Cancer Cells. RDD Europe 2015; 2015: Virginia Commonwealth University.
[57] Bakhtiary Z, Barar J, Aghanejad A, Saei AA, Nemati E, Ezzati Nazhad Dolatabadi J, Omidi Y. Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer. Drug Dev Ind Pharm. 2017; 43(8): 1244-1253. [CrossRef]
[58] Mezzena M, Scalia S, Young PM, Traini D. Solid lipid budesonide microparticles for controlled release inhalation therapy. AAPS J. 2009; 11(4): 771-778. [CrossRef]
[59] Scalia S, Haghi M, Losi V, Trotta V, Young PM, Traini D. Quercetin solid lipid microparticles: a flavonoid for inhalation lung delivery. Eur J Pharm Sci. 2013; 49(2): 278–285. [CrossRef]
[60] Maretti E, Rossi T, Bondi M, Croce MA, Hanuskova M, Leo E, Sacchetti F, Iannuccelli V. Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis. Int J Pharm. 2014; 462(1): 74–82. [CrossRef]
[61] Moreno-Sastre M, Pastor M, Esquisabel A, Sans E, Viñas M, Fleischer A, et al. Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2016; 498(1): 263–273. [CrossRef]
[62] Patil-Gadhe A, Pokharkar V. Pulmonary targeting potential of rosuvastatin loaded nanostructured lipid carrier: Optimization by factorial design. Int J Pharm. 2016; 501(1): 199–210. [CrossRef]
[63] Wang Y, Kho K, Cheow WS, Hadinoto K. A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid–polymer hybrid nanoparticles. Int J Pharm. 2012; 424(1–2): 98–106. [CrossRef]
[64] Yang Y, Cheow WS, Hadinoto K. Dry powder inhaler formulation of lipid–polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles. Int J Pharm. 2012; 434(1): 49–58. [CrossRef]
[65] Bhardwaj A, Mehta S, Yadav S, Singh SK, Grobler A, Goyal AK, Mehta A. Pulmonary delivery of antitubercular drugs using spray-dried lipid–polymer hybrid nanoparticles. Artif Cells Nanomed Biotechnol. 2016; 44(6): 1544–1555. [CrossRef]
[66] Jaspart S, Bertholet P, Piel G, Dogné JM, Delattre L, Evrard B. Solid lipid microparticles as a sustained release system for pulmonary drug delivery. Eur J Pharm Biopharm. 2007; 65(1): 47–56. [CrossRef]
[67] Sanna V, Kirschvink N, Gustin P, Gavini E, Roland I, Delattre L, Evrard B. Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech. 2004; 5(2): 17–23. [CrossRef]
[68] Chougule M, Padhi B, Misra A. Nano-liposomal dry powder inhaler of tacrolimus: preparation, characterization, and pulmonary pharmacokinetics. Int J Nanomedicine. 2007; 2(4): 675.
[69] Chougule M, Padhi B, Misra A. Development of spray dried liposomal dry powder inhaler of dapsone. AAPS PharmSciTech. 2008; 9(1): 47–53. [CrossRef]
[70] Changsan N, Chan H-K, Separovic F, Srichana T. Physicochemical characterization and stability of rifampicin liposome dry powder formulations for inhalation. J Pharm Sci. 2009; 98(2): 628–639. [CrossRef]
[71] Shah SP, Misra A. Liposomal amikacin dry powder inhaler: effect of fines on in vitro performance. AAPS PharmSciTech. 2004; 5(4): 107–113. [CrossRef]
[72] Bi R, Shao W, Wang Q, Zhang N. Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery. J Drug Target. 2008; 16(9): 639–648. [CrossRef]
[73] Shah SP, Misra A. Development of liposomal amphotericin B dry powder inhaler formulation. Drug Deliv. 2004; 11(4): 247–253. [CrossRef]
[74] Joshi MR, Misra A. Liposomal budesonide for dry powder inhaler: preparation and stabilization. AAPS PharmSciTech. 2001; 2(4): 44–53. [CrossRef]
[75] Sweeney LG, Wang Z, Loebenberg R, Wong JP, Lange CF, Finlay WH. Spray-freeze-dried liposomal ciprofloxacin powder for inhaled aerosol drug delivery. Int J Pharm. 2005; 305(1–2): 180–185. [CrossRef]
[76] Huang WH, Yang ZJ, Wu H, Wong YF, Zhao ZZ, Liu L. Development of liposomal salbutamol sulfate dry powder inhaler formulation. Biol Pharm Bull. 2010; 33(3): 512–517. [CrossRef]
[77] Nemati E, Mokhtarzadeh A, Panahi-Azar V, Mohammadi A, Hamishehkar H, Mesgari-Abbasi M, Ezzati Nazhad Dolatabadi J, de la Guardia M. Ethambutol-loaded solid lipid nanoparticles as dry powder inhalable formulation for tuberculosis therapy. AAPS PharmSciTech. 2019; 20(3): 120. [CrossRef]
[78] Ezzati Nazhad Dolatabadi J, Hamishehkar H, Valizadeh H. Development of dry powder inhaler formulation loaded with alendronate solid lipid nanoparticles: solid-state characterization and aerosol dispersion performance. Drug Dev Ind Pharm. 2015; 41(9): 1431–1437. [CrossRef]
[79] Yang X, Liu Y, Liu C, Zhang N. Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. J Biomed Nanotechnol. 2012; 8(5): 834–842. [CrossRef]
[80] Pilcer G, Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm. 2010; 392(1–2): 1–19. [CrossRef]
[81] Akdag Cayli Y, Sahin S, Buttini F, Balducci AG, Montanari S, Vural I, Oner L. Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients. Drug Dev Ind Pharm. 2017: 1–12. [CrossRef]
[82] Yazdi AK, Smyth HDC. Carrier-free high-dose dry powder inhaler formulation of ibuprofen: physicochemical characterization and in vitro aerodynamic performance. Int J Pharm. 2016; 511(1): 403–414. [CrossRef]
[83] Pilcer G, Vanderbist F, Amighi K. Spray‐ dried carrier‐ free dry powder tobramycin formulations with improved dispersion properties. J Pharm Sci. 2009; 98(4): 1463–1475. [CrossRef]
[84] Raula J, Lähde A, Kauppinen EI. Aerosolization behavior of carrier-free l-leucine coated salbutamol sulphate powders. Int J Pharm. 2009; 365(1): 18–25. [CrossRef]
[85] Raula J, Thielmann F, Naderi M, Lehto V-P, Kauppinen EI. Investigations on particle surface characteristics vs. dispersion behaviour of l-leucine coated carrier-free inhalable powders. Int J Pharm. 2010; 385(1): 79–85. [CrossRef]
[86] Edwards AM, Chir B, Chambers A. Comparison of a lactose-free formulation of sodium cromoglycate and sodium cromoglycate plus lactose in the treatment of asthma. Curr Med Res Opin. 1989; 11(5): 283–92. [CrossRef]
[87] Pilcer G, Sebti T, Amighi K. Formulation and characterization of lipid-coated tobramycin particles for dry powder inhalation. Pharm Res. 2006; 23(5): 931–940. [CrossRef]
[88] Raula J, Rahikkala A, Halkola T, Pessi J, Peltonen L, Hirvonen J, Järvinen K, Laaksonen T, Kauppinen EI. Coated particle assemblies for the concomitant pulmonary administration of budesonide and salbutamol sulphate. Int J Pharm. 2013; 441(1): 248–254. [CrossRef]
[89] Rawat A, Majumder QH, Ahsan F. Inhalable large porous microspheres of low molecular weight heparin: in vitro and in vivo evaluation. J Control Release. 2008; 128(3): 224–232. [CrossRef]
[90] Yamasaki K, Kwok PCL, Fukushige K, Prud’homme RK, Chan HK. Enhanced dissolution of inhalable cyclosporine nano-matrix particles with mannitol as matrix former. Int J Pharm. 2011; 420(1): 34–42. [CrossRef]
[91] Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA. Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A. 2002; 99(19): 12001–12005. [CrossRef]
[92] D’Addio SM, Chan JG, Kwok PC, Benson BR, Prud’homme RK, Chan HK. Aerosol delivery of nanoparticles in uniform mannitol carriers formulated by ultrasonic spray freeze drying. Pharm Res. 2013; 30(11): 2891–2901. [CrossRef]
[93] Cheow WS, Ng ML, Kho K, Hadinoto K. Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants. Int J Pharm. 2011; 404(1–2): 289–300. [CrossRef]
[94] Valero J, Egea MA, Espina M, Gamisans F, Garcia ML. Effect of polymerization coadjuvants on nanocapsule elaboration and triamcinolone entrapment. Drug Dev Ind Pharm. 1996; 22(2): 167–173. [CrossRef]
[95] Feng SS, Mu L, Chen BH, Pack D. Polymeric nanospheres fabricated with natural emulsifiers for clinical administration of an anticancer drug paclitaxel (Taxol®). Mater Sci Eng C. 2002; 20(1–2): 85–92. [CrossRef]
[96] Cheow WS, Li S, Hadinoto K. Spray drying formulation of hollow spherical aggregates of silica nanoparticles by experimental design. Chem Eng Res Design. 2010; 88(5): 673–685. [CrossRef]
[97] Chan HK, Chew NYK. Novel alternative methods for the delivery of drugs for the treatment of asthma. Adv Drug Deliv Rev. 2003; 55(7): 793–805. [CrossRef]
[98] Onoue S, Aoki Y, Kawabata Y, Matsui T, Yamamoto K, Sato H, Yamauchi Y, Yamada S. Development of inhalable nanocrystalline solid dispersion of tranilast for airway inflammatory diseases. J Pharm Sci. 2011; 100(2): 622–633. [CrossRef]
[99] Hu L, Kong D, Hu Q, Gao N, Pang S. Evaluation of high-performance curcumin nanocrystals for pulmonary drug delivery both in vitro and in vivo. Nanoscale Res Lett. 2015; 10(1): 381. [CrossRef]
[100] Al-Hallak MK, Sarfraz MK, Azarmi S, Roa WH, Finlay WH, Löbenberg R. Pulmonary delivery of inhalable nanoparticles: dry powder inhalers. Ther Deliv. 2011; 2(10): 1313–1324. [CrossRef]
[101] Abdelaziz HM, Gaber M, Abd-Elwakil MM, Mabrouk MT, Elgohary MM, Kamel NM, Kabary DM, Freag MS, Samaha MW, Mortada SM, Elkhodairy KA, Fang JY, Elzoghby AO. Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates. J Control Release. 2018; 269: 374–392. [CrossRef]
[102] Yamamoto H, Hoshina W, Kurashima H, Takeuchi H, Kawashima Y, Yokoyama T, Tsujimoto H. Engineering of poly (DL-lactic-co-glycolic acid) nanocomposite particles for dry powder inhalation dosage forms of insulin with the spray-fluidized bed granulating system. Adv Powder Technol. 2007; 18(2): 215-228. [CrossRef]
[103] Kaur R, Garg T, Das Gupta U, Gupta P, Rath G, Goyal AK. Preparation and characterization of spray-dried inhalable powders containing nanoaggregates for pulmonary delivery of anti-tubercular drugs. Artif Cells Nanomed Biotechnol. 2016; 44(1): 182–187. [CrossRef]
[104] Ni R, Zhao J, Liu Q, Liang Z, Muenster U, Mao S. Nanocrystals embedded in chitosan-based respirable swellable microparticles as dry powder for sustained pulmonary drug delivery. Eur J PharmSci. 2017; 99: 137–146. [CrossRef]
[105] Mardani S, Maghsoodi M, Ghanbarzadeh S, Nokhodchi A, Yaqoubi S, Hamishehkar H. Preparation and characterization of celecoxib agglomerated nanocrystals and dry powder inhalation formulations to improve its aerosolization performance: agglomerated celecoxib nanocrystals. Pharm Sci. 2017; 23(4). [CrossRef]
[106] Liu T, Han M, Tian F, Cun D, Rantanen J, Yang M. Budesonide nanocrystal-loaded hyaluronic acid microparticles for inhalation: In vitro and in vivo evaluation. Carbohydr Polym. 2018; 181: 1143–1152. [CrossRef]
[107] Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007; 59(7): 645–666. [CrossRef]
[108] Duchene D, Wouessidjewe D, Ponchel G. Cyclodextrins and carrier systems. J Control Release. 1999; 62(1-2): 263–268. [CrossRef]
[109] Mohtar N, Taylor KMG, Sheikh K, Somavarapu S. Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin. Eur J Pharm Biopharm. 2017; 113: 1–10. [CrossRef]
[110] Kinnarinen T, Jarho P, Järvinen K, Järvinen T. Pulmonary deposition of a budesonide/γ-cyclodextrin complex in vitro. J Control Release. 2003; 90(2): 197-205. [CrossRef]
[111] Cabral-Marques H, Almeida R. Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes. Eur J Pharm Biopharm. 2009; 73(1): 121–129. [CrossRef]
[112] Vozone CM, Marques HMC. Complexation of budesonide in cyclodextrins and particle aerodynamic characterization of the complex solid form for dry powder inhalation. J Incl Phenom Macrocycl Chem. 2002; 44(1): 111–116. [CrossRef]

Details

Primary Language

English

Subjects

Pharmaceutical Biotechnology

Journal Section

Review

Authors

Yagmur Akdag ^*
Türkiye

Publication Date

June 27, 2025

Submission Date

September 9, 2019

Acceptance Date

October 25, 2019

Published in Issue

Year 2019 Volume: 23 Number: 6

IZ

https://izlik.org/JA33SS94EX

Cite

RIS / Bibtex

APA

Akdag, Y. (2025). Development of dry powder inhaler formulations for drug delivery systems. Journal of Research in Pharmacy, 23(6), 973-987. https://izlik.org/JA33SS94EX

AMA

1.Akdag Y. Development of dry powder inhaler formulations for drug delivery systems. J. Res. Pharm. 2025;23(6):973-987. https://izlik.org/JA33SS94EX

Chicago

Akdag, Yagmur. 2025. “Development of Dry Powder Inhaler Formulations for Drug Delivery Systems”. Journal of Research in Pharmacy 23 (6): 973-87. https://izlik.org/JA33SS94EX.

EndNote

Akdag Y (July 1, 2025) Development of dry powder inhaler formulations for drug delivery systems. Journal of Research in Pharmacy 23 6 973–987.

IEEE

[1]Y. Akdag, “Development of dry powder inhaler formulations for drug delivery systems”, J. Res. Pharm., vol. 23, no. 6, pp. 973–987, July 2025, [Online]. Available: https://izlik.org/JA33SS94EX

ISNAD

Akdag, Yagmur. “Development of Dry Powder Inhaler Formulations for Drug Delivery Systems”. Journal of Research in Pharmacy 23/6 (July 1, 2025): 973-987. https://izlik.org/JA33SS94EX.

JAMA

1.Akdag Y. Development of dry powder inhaler formulations for drug delivery systems. J. Res. Pharm. 2025;23:973–987.

MLA

Akdag, Yagmur. “Development of Dry Powder Inhaler Formulations for Drug Delivery Systems”. Journal of Research in Pharmacy, vol. 23, no. 6, July 2025, pp. 973-87, https://izlik.org/JA33SS94EX.

Vancouver

1.Yagmur Akdag. Development of dry powder inhaler formulations for drug delivery systems. J. Res. Pharm. [Internet]. 2025 Jul. 1;23(6):973-87. Available from: https://izlik.org/JA33SS94EX