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Recent Advances in Drug Delivery and Formulation

Author(s): Vinayak D. Kabra, Swaroop R. Lahoti* and Vrashabh V. Sugandhi

DOI: 10.2174/0126673878245506231031124020

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Development of Novel Spray-dried Microparticles to Treat Cystic Fibrosis: A Tri-drug Approach

Page: [286 - 299] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Background: Cystic fibrosis is the predominant autosomal recessive disorder known to reduce life expectancy. Research findings indicate that around 60 to 70% of adult individuals with this condition carry infections of Pseudomonas aeruginosa.

Objective: The ongoing research investigates the potential synergy of merging ivacaftor and ciprofloxacin to address bacterial infections.

Methods: The two drugs were spray-dried into microparticles, which were then coated with Lsalbutamol and were to be delivered by a dry powder inhaler. Microparticles were generated by applying the spray drying method, utilizing bovine serum albumin and L-leucine in their preparation. Additionally, L-salbutamol was mixed and adsorbed onto the surface of the spray-dried microparticles, and it acted as a bronchodilator.

Results: The microparticles produced via spray drying exhibited a particle size measuring 1.6 ± 0.04 μm, along with a polydispersity ratio of 0.33. Their zeta potential measured -27.3 ± 1.1 mV, while the mass median aerodynamic diameter of these microparticles was 3.74 ± 0.08 μm. SEM, XRD, and FTIR studies confirmed the entrapment of ivacaftor and ciprofloxacin. The morphology was observed by SEM and TEM scans. Antibacterial synergy was confirmed through the agar broth and dilution method, and the formulation's safety was established based on the outcomes of the MTT assay.

Conclusion: Using spray-dried microparticles containing ciprofloxacin, ivacaftor, and L-salbutamol presents a novel approach to the treatment of cystic fibrosis.

Graphical Abstract

[1]
Chen Q, Shen Y, Zheng J. A review of cystic fibrosis: Basic and clinical aspects. Animal Model Exp Med 2021; 4(3): 220-32.
[http://dx.doi.org/10.1002/ame2.12180] [PMID: 34557648]
[2]
Elborn JS. Cystic fibrosis. Lancet 2016; 388(10059): 2519-31.
[http://dx.doi.org/10.1016/S0140-6736(16)00576-6] [PMID: 27140670]
[3]
Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet 2021; 397(10290): 2195-211.
[http://dx.doi.org/10.1016/S0140-6736(20)32542-3] [PMID: 34090606]
[4]
Matsui H, Grubb BR, Tarran R, et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 1998; 95(7): 1005-15.
[http://dx.doi.org/10.1016/S0092-8674(00)81724-9] [PMID: 9875854]
[5]
Armstrong DS, Hook SM, Jamsen KM, et al. Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. Pediatr Pulmonol 2005; 40(6): 500-10.
[http://dx.doi.org/10.1002/ppul.20294] [PMID: 16208679]
[6]
Kiedrowski MR, Bomberger JM. Viral-bacterial co-infections in the cystic fibrosis respiratory tract. Front Immunol 2018; 9: 3067.
[http://dx.doi.org/10.3389/fimmu.2018.03067] [PMID: 30619379]
[7]
Crull MR, Somayaji R, Ramos KJ, et al. Changing rates of chronic pseudomonas aeruginosa infections in cystic fibrosis: A population-based cohort study. Clin Infect Dis 2018; 67(7): 1089-95.
[http://dx.doi.org/10.1093/cid/ciy215] [PMID: 29534149]
[8]
Acosta N, Waddell B, Heirali A, et al. Cystic fibrosis patients infected with epidemic Pseudomonas aeruginosa strains have unique microbial communities. Front Cell Infect Microbiol 2020; 10: 173.
[http://dx.doi.org/10.3389/fcimb.2020.00173] [PMID: 32426295]
[9]
Malhotra S, Hayes D Jr, Wozniak DJ. Cystic fibrosis and pseudomonas aeruginosa: The host-microbe interface. Clin Microbiol Rev 2019; 32(3): e00138-18.
[http://dx.doi.org/10.1128/CMR.00138-18] [PMID: 31142499]
[10]
Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019; 37(1): 177-92.
[http://dx.doi.org/10.1016/j.biotechadv.2018.11.013] [PMID: 30500353]
[11]
Yu S, Pu X, Ahmed MU, et al. Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa. Int J Pharm 2021; 610: 121160.
[http://dx.doi.org/10.1016/j.ijpharm.2021.121160] [PMID: 34624446]
[12]
Collins FS. Realizing the dream of molecularly targeted therapies for cystic fibrosis. N Engl J Med 2019; 381(19): 1863-5.
[http://dx.doi.org/10.1056/NEJMe1911602] [PMID: 31670919]
[13]
Allobawi R, Ghelani DP, Schneider-Futschik EK. Metabolomic description of ivacaftor elevating Polymyxin B mediated antibacterial activity in cystic fibrosis Pseudomonas aeruginosa. ACS Pharmacol Transl Sci 2020; 3(3): 433-43.
[http://dx.doi.org/10.1021/acsptsci.0c00030] [PMID: 32566909]
[14]
Reznikov LR, Abou Alaiwa MH, Dohrn CL, et al. Antibacterial properties of the CFTR potentiator ivacaftor. J Cyst Fibros 2014; 13(5): 515-9.
[http://dx.doi.org/10.1016/j.jcf.2014.02.004] [PMID: 24618508]
[15]
Waters V, Smyth A. Cystic fibrosis microbiology: Advances in antimicrobial therapy. J Cyst Fibros 2015; 14(5): 551-60.
[http://dx.doi.org/10.1016/j.jcf.2015.02.005] [PMID: 25737165]
[16]
Scavone C, Mascolo A, Ruggiero R, et al. Quinolones-induced musculoskeletal, neurological, and psychiatric ADRs: A pharmacovigilance study based on data from the italian spontaneous reporting system. Front Pharmacol 2020; 11: 428.
[http://dx.doi.org/10.3389/fphar.2020.00428] [PMID: 32351386]
[17]
Kipnis E, Sawa T, Wiener-Kronish J. Targeting mechanisms of Pseudomonas aeruginosa pathogenesis. Med Mal Infect 2006; 36(2): 78-91.
[http://dx.doi.org/10.1016/j.medmal.2005.10.007] [PMID: 16427231]
[18]
Chono S, Tanino T, Seki T, Morimoto K. Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin for the treatment of respiratory infections. Drug Metab Pharmacokinet 2007; 22(2): 88-95.
[http://dx.doi.org/10.2133/dmpk.22.88] [PMID: 17495415]
[19]
Velino C, Carella F, Adamiano A, et al. Nanomedicine approaches for the pulmonary treatment of cystic fibrosis. Front Bioeng Biotechnol 2019; 7: 406.
[http://dx.doi.org/10.3389/fbioe.2019.00406] [PMID: 31921811]
[20]
Dorkin HL, Staab D, Operschall E, Alder J, Criollo M. Ciprofloxacin DPI: A randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis. BMJ Open Respir Res 2015; 2(1): e000100.
[http://dx.doi.org/10.1136/bmjresp-2015-000100] [PMID: 26688732]
[21]
Flume PA, O’Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007; 176(10): 957-69.
[http://dx.doi.org/10.1164/rccm.200705-664OC] [PMID: 17761616]
[22]
Kieninger E, Willers C, Röthlisberger K, et al. Effect of salbutamol on lung ventilation in children with cystic fibrosis: Comprehensive assessment using spirometry, multiple-breath washout, and functional lung magnetic resonance imaging. Respiration 2022; 101(3): 281-90.
[http://dx.doi.org/10.1159/000519751] [PMID: 34808631]
[23]
Uma Maheswari P, Muthappa R, Bindhya KP, Meera Sheriffa Begum KM. Evaluation of folic acid functionalized BSA-CaFe2O4 nanohybrid carrier for the controlled delivery of natural cytotoxic drugs hesperidin and eugenol. J Drug Deliv Sci Technol 2021; 61: 102105.
[http://dx.doi.org/10.1016/j.jddst.2020.102105]
[24]
Sugandhi VV, Mahajan HS. Development of vitamin B12 containing pullulan-bovine serum albumin microparticles designed dry powder inhaler: In-vitro and in-vivo study. J Drug Deliv Sci Technol 2022; 70: 103212.
[http://dx.doi.org/10.1016/j.jddst.2022.103212]
[25]
Girase ML, Sugandhi VV, Ige PP, Jain PD, Nangare SN. Design of surface tailored carboxymethyl dextran-protein based nanoconjugates for paclitaxel: Spectroscopical characterizations and cytotoxicity assay Int J Biol Macromol 2022; 222(Pt B): 1818-29.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.09.271] [PMID: 36191785]
[26]
Fang Z, Bhandari B. Effect of spray drying and storage on the stability of bayberry polyphenols. Food Chem 2011; 129(3): 1139-47.
[http://dx.doi.org/10.1016/j.foodchem.2011.05.093] [PMID: 25212349]
[27]
Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res 2008; 25(5): 999-1022.
[http://dx.doi.org/10.1007/s11095-007-9475-1] [PMID: 18040761]
[28]
Shetty N, Cipolla D, Park H, Zhou QT. Physical stability of dry powder inhaler formulations. Expert Opin Drug Deliv 2020; 17(1): 77-96.
[http://dx.doi.org/10.1080/17425247.2020.1702643] [PMID: 31815554]
[29]
Wolska E. Fine powder of lipid microparticles-spray drying process development and optimization. J Drug Deliv Sci Technol 2021; 64: 102640.
[http://dx.doi.org/10.1016/j.jddst.2021.102640]
[30]
Alyami H, Dahmash E, Bowen J, Mohammed AR. An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug. PLoS One 2017; 12(6): e0178772.
[http://dx.doi.org/10.1371/journal.pone.0178772] [PMID: 28609454]
[31]
Tozar T, Boni M, Staicu A, Pascu ML. Optical characterization of Ciprofloxacin photolytic degradation by UV-pulsed laser radiation. Molecules 2021; 26(8): 2324.
[http://dx.doi.org/10.3390/molecules26082324] [PMID: 33923649]
[32]
Gadekar GR, Patil SS, Shah RR, Ghodke DS. Development and validation of a simple uv spectrophotometric method for the estimation of salbutamol sulphate from pharmaceutical formulations. Int J Curr Pharm Res 2019; 72-5.
[http://dx.doi.org/10.22159/ijcpr.2019v11i5.35707]
[33]
Nangare S, Dugam S, Patil P, Tade R, Jadhav N. Silk industry waste protein: Isolation, purification and fabrication of electrospun silk protein nanofibers as a possible nanocarrier for floating drug delivery. Nanotechnology 2021; 32(3): 035101.
[http://dx.doi.org/10.1088/1361-6528/abb8a9] [PMID: 32932237]
[34]
Radivojev S, Luschin-Ebengreuth G, Pinto JT, et al. Impact of simulated lung fluid components on the solubility of inhaled drugs and predicted in vivo performance. Int J Pharm 2021; 606: 120893.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120893] [PMID: 34274456]
[35]
Sudarshan S, Sunil BB. In vivo mucoadhesive strength appraisal of gum Manilkara zapota. Braz J Pharm Sci 2015; 51(3): 689-98.
[http://dx.doi.org/10.1590/S1984-82502015000300021]
[36]
Herrera LC, Tesoriero MV, Hermida LG. In vitro release testing of PLGA microspheres with franz diffusion cells. Dissolut Technol 2012; 19(2): 6-11.
[http://dx.doi.org/10.14227/DT190212P6]
[37]
Bruschi ML. Ed. 5 - Mathematical models of drug release. Strategies to Modify the Drug Release from Pharmaceutical Systems. Woodhead Publishing 2015; pp. 63-86. https://www.sciencedirect.com/science/article/pii/B9780081000922000059 Internet
[http://dx.doi.org/10.1016/B978-0-08-100092-2.00005-9]
[38]
Wiegand I, Hilpert K, Hancock REW. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 2008; 3(2): 163-75.
[http://dx.doi.org/10.1038/nprot.2007.521] [PMID: 18274517]
[39]
Wijesinghe G, Dilhari A, Gayani B, Kottegoda N, Samaranayake L, Weerasekera M. Influence of laboratory culture media on in vitro growth, adhesion, and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus. Med Princ Pract 2019; 28(1): 28-35.
[http://dx.doi.org/10.1159/000494757] [PMID: 30352435]
[40]
Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int J Mol Sci 2021; 22(23): 12827.
[http://dx.doi.org/10.3390/ijms222312827] [PMID: 34884632]
[41]
Rogueda PGA, Traini D. The nanoscale in pulmonary delivery. Part 1: deposition, fate, toxicology and effects. Expert Opin Drug Deliv 2007; 4(6): 595-606.
[http://dx.doi.org/10.1517/17425247.4.6.595] [PMID: 17970663]
[42]
Yang W, Peters JI, Williams RO III. Inhaled nanoparticles—A current review. Int J Pharm 2008; 356(1-2): 239-47.
[http://dx.doi.org/10.1016/j.ijpharm.2008.02.011] [PMID: 18358652]
[43]
Zellmer S, Garnweitner G, Breinlinger T, Kraft T, Schilde C. Hierarchical structure formation of nanoparticulate spray-dried composite aggregates. ACS Nano 2015; 9(11): 10749-57.
[http://dx.doi.org/10.1021/acsnano.5b05220] [PMID: 26505280]
[44]
Kabra VD, Lahoti SR. Novel therapeutic approach for the treatment of cystic fibrosis based on freeze-dried tridrug microparticles to treat cystic fibrosis. DARU J Pharm Sci 2023 Jun 1 31(1): 39-50. Available at: https://link.springer.com/article/10.1007/s40199-023-00460-4?code=1f7f4339-7ee6-441a-8349-ad26548e04e8&error=cookies_not_supported
[45]
Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: Formulation, process and storage considerations. Adv Drug Deliv Rev 2006; 58(15): 1688-713.
[http://dx.doi.org/10.1016/j.addr.2006.09.017] [PMID: 17118485]
[46]
Wu L, Miao X, Shan Z, et al. Studies on the spray dried lactose as carrier for dry powder inhalation. Asian Journal of Pharmaceutical Sciences 2014; 9(6): 336-41.
[http://dx.doi.org/10.1016/j.ajps.2014.07.006]
[47]
Aranaz I, Paños I, Peniche C, Heras Á, Acosta N. Chitosan spray-dried microparticles for controlled delivery of venlafaxine hydrochloride. Molecules 2017; 22(11): 1980.
[http://dx.doi.org/10.3390/molecules22111980] [PMID: 29140306]
[48]
Aramwit P. 2016.https://www.sciencedirect.com/science/article/pii/B9781782424567000015
[49]
Choi SH, Byeon HJ, Choi JS, et al. Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer. J Control Release 2015; 197: 199-207.
[http://dx.doi.org/10.1016/j.jconrel.2014.11.008] [PMID: 25445703]
[50]
Yu Z, Yu M, Zhang Z, Hong G, Xiong Q. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear. Nanoscale Res Lett 2014; 9(1): 343.
[http://dx.doi.org/10.1186/1556-276X-9-343] [PMID: 25114637]
[51]
Wang W, Lei Y, Sui H, et al. Fabrication and evaluation of nanoparticle-assembled BSA microparticles for enhanced liver delivery of glycyrrhetinic acid. Artif Cells Nanomed Biotechnol 2017; 45(4): 740-7.
[http://dx.doi.org/10.1080/21691401.2016.1193024] [PMID: 27267996]
[52]
Lee G. Spray-drying of proteins 2002.
[http://dx.doi.org/10.1007/978-1-4615-0557-0_6]
[53]
Pedrozo RC, Antônio E, Khalil NM, Mainardes RM. Bovine serum albumin-based nanoparticles containing the flavonoid rutin produced by nano spray drying. Braz J Pharm Sci 2020; 56: e17692.http://www.scielo.br/j/bjps/a/8CmgtXcTJCqpRtMrSTcrprp/ [Internet].
[http://dx.doi.org/10.1590/s2175-97902019000317692]
[54]
Nettey H, Haswani D, Oettinger CW, D’Souza MJ. Formulation and testing of vancomycin loaded albumin microspheres prepared by spray-drying. J Microencapsul 2006; 23(6): 632-42.
[http://dx.doi.org/10.1080/02652040600776564] [PMID: 17118879]
[55]
Mangal S, Meiser F, Tan G, et al. Relationship between surface concentration of l-leucine and bulk powder properties in spray dried formulations. Eur J Pharm Biopharm 2015; 94: 160-9.
[http://dx.doi.org/10.1016/j.ejpb.2015.04.035] [PMID: 26007290]
[56]
Thiyagarajan D, Huck B, Nothdurft B, et al. Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals. Drug Deliv Transl Res 2021; 11(4): 1766-78.
[http://dx.doi.org/10.1007/s13346-021-01011-7] [PMID: 34101127]
[57]
Xu Y, Harinck L, Lokras AG, et al. Leucine improves the aerosol performance of dry powder inhaler formulations of siRNA-loaded nanoparticles. Int J Pharm 2022; 621: 121758.
[http://dx.doi.org/10.1016/j.ijpharm.2022.121758] [PMID: 35483619]
[58]
Party P, Kókai D, Burián K, Nagy A, Hopp B, Ambrus R. Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: in vitro aerodynamic and cell line measurements. Eur J Pharm Sci 2022; 176: 106247.
[http://dx.doi.org/10.1016/j.ejps.2022.106247] [PMID: 35760279]
[59]
Wang X, Wan W, Lu J, Quan G, Pan X, Liu P. Effects of L-leucine on the properties of spray-dried swellable microparticles with wrinkled surfaces for inhalation therapy of pulmonary fibrosis. Int J Pharm 2021; 610: 121223.
[http://dx.doi.org/10.1016/j.ijpharm.2021.121223] [PMID: 34710541]
[60]
Momin MAM, Rangnekar B, Sinha S, Cheung CY, Cook GM, Das SC. Inhalable dry powder of bedaquiline for pulmonary tuberculosis: In vitro physicochemical characterization, antimicrobial activity and safety studies. Pharmaceutics 2019; 11(10): 502.
[http://dx.doi.org/10.3390/pharmaceutics11100502] [PMID: 31581469]
[61]
Lu P, Xing Y, Peng H, et al. Physicochemical and pharmacokinetic evaluation of spray-dried coformulation of Salvia miltiorrhiza polyphenolic acid and L-leucine with improved bioavailability. J Aerosol Med Pulm Drug Deliv 2020; 33(2): 73-82.
[http://dx.doi.org/10.1089/jamp.2019.1538] [PMID: 31660760]
[62]
Alhajj N, O’Reilly NJ, Cathcart H. Leucine as an excipient in spray dried powder for inhalation. Drug Discov Today 2021; 26(10): 2384-96.
[http://dx.doi.org/10.1016/j.drudis.2021.04.009] [PMID: 33872799]
[63]
Liu M, Dasgupta A, Qu N, Rama E, Kiessling F, Lammers T. Strategies to Maximize Anthracycline Drug Loading in Albumin Microbubbles. ACS Biomater Sci Eng 2021; 1c01203. acsbiomaterials
[http://dx.doi.org/10.1021/acsbiomaterials.1c01203] [PMID: 34931809]
[64]
Chablani L, Tawde SA, D’souza MJ. Spray-dried microparticles: a potential vehicle for oral delivery of vaccines. J Microencapsul 2012; 29(4): 388-97.
[http://dx.doi.org/10.3109/02652048.2011.651503] [PMID: 22283700]
[65]
Smith S, Rowbotham NJ, Edwards CT. Short-acting inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2022; 6(6): CD013666.
[PMID: 35749226]
[66]
Isawa T, Teshima T, Hirano T, Ebina A, Konno K. Effect of oral salbutamol on mucociliary clearance mechanisms in the lungs. Tohoku J Exp Med 1986; 150(1): 51-61.
[http://dx.doi.org/10.1620/tjem.150.51] [PMID: 3775772]
[67]
Zheng Z, Leung SSY, Gupta R. Flow and particle modelling of dry powder inhalers: Methodologies, recent development and emerging applications. Pharmaceutics 2021; 13(2): 189.
[http://dx.doi.org/10.3390/pharmaceutics13020189] [PMID: 33535512]
[68]
Courrier HM, Butz N, Vandamme TF. 2002.https://www. dl.begellhouse.com/journals/3667c4ae6e8fd136,69e332455d956168,36cf2510466cdf35.html
[69]
Takechi-Haraya Y, Ohgita T, Demizu Y, Saito H, Izutsu K, Sakai-Kato K. Current status and challenges of analytical methods for evaluation of size and surface modification of nanoparticle-based drug formulations. AAPS PharmSciTech 2022; 23(5): 150.
[http://dx.doi.org/10.1208/s12249-022-02303-y] [PMID: 35596094]
[70]
Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol 2011; 697: 63-70.
[http://dx.doi.org/10.1007/978-1-60327-198-1_6] [PMID: 21116954]
[71]
Tarhini M, Pizzoccaro A, Benlyamani I, et al. Human serum albumin nanoparticles as nanovector carriers for proteins: Application to the antibacterial proteins “neutrophil elastase” and “secretory leukocyte protease inhibitor”. Int J Pharm 2020; 579: 119150.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119150] [PMID: 32070757]
[72]
Edsman K, Hägerström H. Pharmaceutical applications of mucoadhesion for the non-oral routes. J Pharm Pharmacol 2010; 57(1): 3-22.
[http://dx.doi.org/10.1211/0022357055227] [PMID: 15638988]
[73]
Dimer F, de Souza Carvalho-Wodarz C, Haupenthal J, Hartmann R, Lehr CM. Inhalable clarithromycin microparticles for treatment of respiratory infections. Pharm Res 2015; 32(12): 3850-61.
[http://dx.doi.org/10.1007/s11095-015-1745-8] [PMID: 26113237]
[74]
Scherließ R, Bock S, Bungert N, Neustock A, Valentin L. Particle engineering in dry powders for inhalation. Eur J Pharm Sci 2022; 172: 106158.
[http://dx.doi.org/10.1016/j.ejps.2022.106158] [PMID: 35248734]
[75]
Najafabadi AR, Gilani K, Barghi M, Rafiee-Tehrani M. The effect of vehicle on physical properties and aerosolisation behaviour of disodium cromoglycate microparticles spray dried alone or with l-leucine. Int J Pharm 2004; 285(1-2): 97-108.
[http://dx.doi.org/10.1016/j.ijpharm.2004.07.027] [PMID: 15488683]
[76]
Melzig S, Niedbalka D, Schilde C, Kwade A. Spray drying of amorphous ibuprofen nanoparticles for the production of granules with enhanced drug release. Colloids Surf A Physicochem Eng Asp 2018; 536: 133-41.
[http://dx.doi.org/10.1016/j.colsurfa.2017.07.028]
[77]
Guan J, Yuan H, Yu S, Mao S, Tony Zhou Q. Spray dried inhalable ivacaftor co-amorphous microparticle formulations with leucine achieved enhanced in vitro dissolution and superior aerosol performance. Int J Pharm 2022; 622: 121859.
[http://dx.doi.org/10.1016/j.ijpharm.2022.121859] [PMID: 35643348]
[78]
Bhongade B, Talath S, Dhaneshwar S. A validated method for the quantitation of ciprofloxacin hydrochloride using diffuse reflectance infrared fourier transform spectroscopy. Int J Spectrosc 2014; 2014: 1-6.
[http://dx.doi.org/10.1155/2014/294612]
[79]
Cho DY, Lim DJ, Mackey C, et al. Ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, enhances ciprofloxacin activity Against Pseudomonas aeruginosa. Am J Rhinol Allergy 2019; 33(2): 129-36.
[http://dx.doi.org/10.1177/1945892418815615] [PMID: 30585080]
[80]
Li W, Zhou J, Xu Y. Study of the in vitro cytotoxicity testing of medical devices. Biomed Rep 2015; 3(5): 617-20.
[http://dx.doi.org/10.3892/br.2015.481] [PMID: 26405534]
[81]
Chai G, Park H, Yu S, et al. Evaluation of co-delivery of colistin and ciprofloxacin in liposomes using an in vitro human lung epithelial cell model. Int J Pharm 2019; 569: 118616.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118616] [PMID: 31415873]