Development of Triamcinolone Acetonide Loaded Poly(lactide-co-glycolic acid) Dry Powder Inhaler Formulations For The Treatment of Asthma

Yıl 2022, Cilt: 12 Sayı: 1, 249 - 256, 30.03.2022

Aysu Yurdasiper

https://doi.org/10.33808/clinexphealthsci.1015166

Cited By: 1

Öz

Objective: The objective of this study was to develop triamcinolone acetonide (TAA) loaded poly(lactide-co-glycolic acid) (PLGA) dry powder inhaler (DPI) formulations by using spray dryer and to characterize the formulations with reference to their appropriateness for pulmonary drug delivery.
Methods: PLGA dry powder inhalers containing TAA were produced in two stages. In the first step, PLGA microparticles were prepared by emulsion-solvent evaporation method and the DPI formulations were produced by the spray-drying process using mannitol and leucine. TAA loaded PLGA DPI was classified physicochemical properties. The in vitro dissolution test was carried out using modified USP apparatus 2. Aerosol performance was identified with next generation impactor.
Results: This study has demonstrated that TAA loaded PLGA DPI were effectively prepared. Scanning electron microscope illustrates the spherical shape, particle size (D50) was established to be between 2.7-3.1 µm and all formulations charged negatively. Special chemical interaction in the DPI was not observed by FT-IR. The in vitro aerosol performance study represented DPI formulations have the proper aerodynamic properties for targeting the lungs. The in vitro TAA release from DPI formulations decreased with increasing of PLGA concentration.
Conclusion: Developed PLGA dry powder inhaler formulations containing TAA have shown suitable aerodynamic characteristics to be administered to the lungs thereby could improve in the management of asthma by increasing TAA residency in the lungs for a prolonged period of time.

Anahtar Kelimeler

Triamcinolone acetonide, pulmonary drug delivery, dry powder inhaler formulations, poly(lactide-co-glycolic acid), spray dryer

Destekleyen Kurum

Ege University Project Coordination Center

Proje Numarası

13/ECZ/017

Teşekkür

The author would like to acknowledge Assist. Prof. Dr. Özlem Akgül for the interpretation of FT-IR experiments and Dr. Mehmet Ali Ege, Assoc. Prof. Dr. Aylin Arıcı for assisting in performing the statistical analyses.

Kaynakça

• Quirce S, Heffler E, Nenasheva N, Demoly P, Menzies-Gow A, Moreira-Jorge A, Nissen F, Hanania NA. Revisiting late-onset asthma: Clinical characteristics and association with allergy. J Asthma Allergy 2020;13:743-752.
• Ye Q, He XO, D’Urzo A. A Review on the safety and efficacy of inhaled corticosteroids in the management of asthma. Pulm Ther 2017;3:1–18.
• Zanen P, Go LT, Lammers JWJ. The optimal particle-size for beta-adrenergic aerosols in mild asthmatics. Int J Pharmaceutics 1994;107:211–217.
• Galvan CA, Guarderas JC. Practical considerations for dysphonia caused by inhaled corticosteroids. Mayo Clin Proc 2012;87(9):901-904.
• Hirst PH, Pitcairn GR, Richards JC, Rohatagi S, Gillen MS, Newman SP. Deposition and pharmacokinetics of an HFA formulation of triamcinolone acetonide delivered by pressurized metered dose inhaler. J Aerosol Med 2001;14(2), 155–165.
• Argenti D, Shah B, Heald D. A pharmacokinetic study to evaluate the absolute bioavailability of triamcinolone acetonide following inhalation administration. J Clin Pharmacology 1999;39:695-702.
• Eroglu H, Haidar MK, Nemutlu E, Ozturk S, Bayram C, Ulubayram K, Oner L. Dual release behavior of atorvastatin and alpha-lipoic acid from PLGA microspheres for the combination therapy in peripheral nerve injury. J Drug Del Sci Tech 2017;39:455-466.
• Fantini A, Padula C, Nicoli S, Pescina S, Santi P. The role of vehicle metamorphosis on triamcinolone acetonide delivery to the skin from microemulsions. Int J of Pharm 2019;565:33-40.
• Hamishehkar H, Emami J, Najafabadi AR, Gilani K, Minaiyan M, Hassanzadeh K, Mahdavi H, Koohsoltani M, Nokhodchi A. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats. Biopharm Drug Dispos 2010;31:189–201.
• Yalcin TE, Tamer SI, Takka S. Effect of organic solvents on gemcitabine loaded PLGA nanoparticles. FABAD J Pharm Sci 2017;42:15-19.
• Scherließ R, Janke J. Preparation of poly-lactic-coglycolic acid nanoparticles in a dry powder formulation for pulmonary antigen delivery. Pharmaceutics 2021;13:1196.
• Son YJ, McConville J.T. Development of a standardized dissolution test method for inhaled pharmaceutical formulations. Int J Pharm 2009;382(1-2):15–22.
• Dantas D, Pasquali MA, Cavalcanti-Mata M, Duarte ME, Lisboa HM. Influence of spray drying conditions on the properties of avocado powder drink. Food Chem 2018;266:284–291.
• Silverstein RM, Webster FX, Kiemle DJ. Spectrometric identification of organic compounds. John Wiley & Sons, Inc., editors. Hoboken 2005.p.1-550.
• Yildiz A, John E, Ozsoy Y, Araman A, Birchall JC, Broadley KJ, Gumbleton M. Inhaled extended-release microparticles of heparin elicit improved pulmonary pharmacodynamics against antigen-mediated airway hyper-reactivity and inflammation. J Control Release 2012;162(2):456-463.
• Lu W, Rades T, Rantanen J, Yang M. Inhalable co-amorphous budesonide-arginine dry powders prepared by spray drying. Int J Pharmaceutics 2019;565:1–8.
• Momin MAM, Tucker IG, Doyle CS, Denman JA, Das SC. Manipulation of spray-drying conditions to develop dry powder particles with surfaces enriched in hydrophobic material to achieve high aerosolization of a hygroscopic drug. Int J Pharmaceutics 2018;543(1-2):318–327.
• Varshosaz J, Taymouri S, Hamishehkar H, Vatankhah R, Yaghubi S. Development of dry powder inhaler containing tadalafil-loaded PLGA nanoparticles, Res Pharm Sci 2017;12(3):222-232.
• D’Aurizio E, Van Nostrum CF, Van Steenbergen MJ, Sozio P, Siepmann F, Siepmann J, Hennink WE, Di Stefano A. Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug. Int J Pharm 2011;409:289–296.
• Su Y, Zhang B, Sun R, Liu W, Zhu Q, Zhang X, Wang R, Chen C. PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application. Drug Delivery 2021;28:(1)1397-1418.
• Panyam J, William D, Dash A, Leslie-Pelecky D, Labhasetwar V. Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J of Pharm Sci 2004;93(7):1804–1814.
• Price R, Young PM, Edge S, Staniforth JN. The influence of relative humidity on particulate interactions in carrier-based dry powder inhaler formulations. Int. J Pharm 2002;246:47–59.
• Han FY, Thurecht KJ, Whittaker AK, Smith MT. Bioerodable PLGA-based microparticles for producing sustained-release drug formulations and strategies for improving drug loading. Front Pharmacol 2016;7(185):1-11.
• Kim J, Lee B, Lee J, Ji M, Park CS, Lee J, Kang M, Kim J, Jin M, Kim HH. N-Glycan modifications with negative charge in a natural polymer mucin from bovine submaxillary glands, and their structural role. Polymers (Basel) 2020;13(1):103.
• Mali AJ, Pawar AP, Purohit RN. Development of budesonide loaded biopolymer based dry powder inhaler: optimization, in vitro deposition, and cytotoxicity study. Journal of Pharmaceutics 2014; Article ID 795371.
• Cayli YA, 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;43(8):1378-1389.
• Alhajj N, O'Reilly NJ, Cathcart H. Leucine as an excipient in spray dried powder for inhalation. Drug Discovery Today 2021;26(10):2384-2396.
• Devrim B, Bozkir A, Canefe K. Preparation and evaluation of poly(lactic-co-glycolic acid) microparticles as a carrier for pulmonary delivery of recombinant human interleukin-2: II. In vitro studies on aerodynamic properties of dry powder inhaler formulations, Drug Dev Ind Pharm 2011;37(11):1376-1386.
• Scichilone N, Spatafora M, Battaglia S, Arrigo R, Benfante A, Bellia V. Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations. J Asthma Allergy 2013;6:11-21.
• Zhang Y, Zhang R, Illangakoon UE, Harker AH, Thrasivoulou C, Parhizkar M, Edirisinghe M, Luo CJ. Copolymer composition and nanoparticle configuration enhance in vitro drug release behavior of poorly water-soluble progesterone for oral formulations. Int J Nanomedicine 2020;15:5389-5403.
• Yao S, Liu H, Yu S, Li Y, Wang X, Wang L, Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior. Regenerative Biomaterials 2016;3(5):309–317.