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Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Formulation of Dry Powder Inhaler of Anti-tuberculous Drugs Using Spray Drying Technique and Optimization Using 23 Level Factorial Design Approach

Author(s): Vaishali Thakkar*, Ekta Pandey, Tosha Pandya, Purvi Shah, Asha Patel, Roma Trivedi, Mukesh Gohel, Lalji Baldaniya and Tejal Gandhi

Volume 14, Issue 3, 2019

Page: [239 - 260] Pages: 22

DOI: 10.2174/1574885514666190104114209

Price: $65

Abstract

Background: Targeting anti-tubercular therapeutics to alveolar macrophages using microparticles technology mainly focuses on increasing local concentrations of therapeutics and potentially reducing the frequency of dosing requirements. Rifampicin (RIF), Ofloxacin (OFX) and Ethambutol (ETH) combination show synergism.

Objective: In light of the above facts, the focus of the present study was to develop and characterize novel Dry powder Inhaler formulation incorporating novel drug combination as a pulmonary delivery for the effective eradication of Tuberculosis.

Method: Biodegradable microparticles containing RIF, OFX and ETH were prepared by a spray drying technique using PLGA polymer through the critical process as well as polymer attributes were screened and optimized using 23 factorial design. The identified critical process parameters (CPP’s) viz. Inlet temperature, Aspiration rate, and feed rate were selected as independent variables while percentage yield, percentage entrapment efficiency, and particle size were selected as a response. The formulated microparticles were evaluated for particle size, drug-polymer compatibility study, aerodynamic behavior, morphology, particle size distribution, crystallinity, residual solvent content, in-vitro drug release study, and stability study.

Results: By choosing the optimum spray drying conditions maximum yield of 73%, entrapment efficiency of 86% and particle size of 1.4 μm was attained of the optimized batch. Thus the results revealed that spherical microparticles are suitable for inhalation and sustained release for 12 h.

Conclusion: The successful formulation and evaluation of dry powder could be used as an enhanced therapeutic alternative of the standard oral anti-tubercular regimen, rescuing oral dosing, shortening drug regimen and limiting toxicity. This will ultimately improve patient compliance and diminish the prevalence of MDR resistance.

Keywords: Dry powder inhaler, tuberculosis, PLGA, Spray drying, 23 factorial design, optimization.

Graphical Abstract
[1]
World Health Organization. Global tuberculosis report. 2017; Geneva, Switzerland: WHO.
[2]
Advaryu M, Vakharia B. Drug-resistance tuberculosis: emerging treatment options: a review. Clin Pharmacol Adv Appl 2011; 3: 51-67.
[3]
Palmero D, Cruz V, Museli T, Pavlovsky H, Fernández J, Waisman J. Adverse drug reactions in multidrug-resistant tuberculosis. Medicina (B Aires) 2010; 70: 427-33.
[4]
Patil-Gadhe AA, Kyadarkunte AY, Pereira M, et al. Rifapentine-proliposomes for inhalation: In vitro and in vivo toxicity. Toxicol Int 2014; 21: 275-82.
[5]
Pandey R, Khuller GK. Antitubercular inhaled therapy: opportunities, progress and challenges. J Antimicrob Chemother 2005; 55: 430-5.
[6]
Sharma R, Muttil P, Yadav AB, et al. Uptake of inhalable microparticles affects defence responses of macrophages infected with Mycobacterium tuberculosis H37Ra. J Antimicrob Chemother 2007; 59: 499-506.
[7]
Rey-Jurado E, Tudo G, Martinez JA, Gonzalez-Martín J. Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis. Tuberculosis 2012; 92: 260-3.
[8]
Surber MW, Bostian KA, Dudley MN, Lomovskaya O, Griffith DC. Aerosolized fluoroquinolones and uses thereof United States patent US 0166673 A1, 2010.
[9]
Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolone, tuberculosis, and resistance. Lancet Infect Dis 2013; 3: 432-42.
[10]
Takiff H, Guerrero E. Current prospects for the Fluoroquinolones as First-line Tuberculosis Therapy. Antimicrob Agents Chemother 2011; 55: 5421-9.
[11]
Makadia HK, Siegel SJ. Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 2011; 3: 1377-97.
[12]
Verma R, Singh A, Mohan M, et al. Inhalable microparticles containing nitric oxide donors: saying NO to intracellular Mycobacterium tuberculosis. Mol Pharm 2012; 9: 3183-9.
[13]
Koch K, Dew B, Corcoran T, Przybycien T, Tilton R, Garoff S. Surface tension gradient driven spreading on aqueous mucin solutions: a possible route to enhanced pulmonary drug delivery. Mol Pharm 2011; 8: 387-94.
[14]
Ashurst I, Malton A, Prime D, Sumby B. Latest advances in the development of dry powder inhalers. Pharm Sci Technol Today 2000; 3: 246-56.
[15]
Rattanupatam T, Srichana T. Budesonide dry powder for inhalation: effects of leucine and mannitol on the efficiency of delivery. Drug Deliv 2014; 21: 397-405.
[16]
Marques H, Almeida R. Optimization of spray-drying process variables for dry powder inhalation (DPI) formulation of corticosteroid/cyclodextrin inclusion complexes. Eur J Pharm Biopharm 2009; 73: 121-9.
[17]
Kumaresan C, Sathishkumar K. Development of an inhaled sustained release dry powder formulation of salbutamol sulphate, an antiasthmatic drug. Indian J Pharm Sci 2016; 78: 136-42.
[18]
Ozeki T, Tagami T. Drug/polymer nanoparticles prepared using unique spray nozzles and recent progress of inhaled formulation. Asian J Pharmac Sci 2014; 9: 236-43.
[19]
Tamura G, Sakae H, Fujino S. In vitro evaluation of dry powder inhaler devices of corticosteroid preparations. Allergol Int 2012; 61: 149-54.
[20]
Rahimpour Y, Hamishehkar H. Lactose engineering for better performance in dry powder inhalers. Adv Pharm Bull 2012; 2: 183-7.
[21]
Vaghani D, Patel A, Thakkar V, Gohel M. Exploring polymeric nano-particles as targeted pulmonary delivery of Rifampicin, Ethambutol and Ofloxacin against Inh-Resistant Tuberculosis. J Lung Pulm Respir Res 2017; 4: 00116.
[22]
Mokale V, Rajput R, Patil J, Yadava S, Naik J. Formulation of metformin hydrochloride nanoparticles by using spray drying technique and in-vitro evaluation of sustained release with 32-level factorial design approach. Dry Technol 2016; 34: 1455-61.
[23]
Mehta P. Dry powder inhalers: A focus on advancements in novel drug delivery systems. J Drug Deliv 2016; 20168290963

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