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Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis.
Int J Pharm. 2016 Jun 15; 506(1-2):174-83.IJ

Abstract

Sterilization of necrotic granulomas containing Mycobacterium tuberculosis is difficult by oral and parenteral drug delivery of antitubercular drugs. Pulmonary delivery of these drugs should increase the concentration of drug in the granulomas and, thereby, improve the sterilization. The current study aimed to develop spray-dried (SD) powders composed of pyrazinamide, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine N-(carbonyl-methoxy polyethylene glycol-2000) (DSPE-PEG2k) and l-leucine to improve drug delivery to the deeper lung. Pyrazinamide SD powders with varying amounts of DPPC (5, 15 and 25% w/w) were produced using a BUCHI B-290 Mini Spray-Dryer. The powders were characterized physicochemically and for their aerosol dispersion performance using a Next Generation Impactor (NGI). All the SD powders had a narrow particle size distribution (1.29-4.26μm) with low residual moisture (<2%). Solid state characterization confirmed that the α-polymorphic crystalline pyrazinamide transformed into the γ-polymorphic form during spray-drying. SD pyrazinamide (PDDL0) without excipients showed very poor aerosolization with a fine particle fraction (FPF%) of 8.5±1.0%. However, the SD powder with 25% w/w DPPC (PDDL3) exhibited the best aerosolization with a FPF of 73.2±4.0%. Incorporating high amounts of DPPC improved aerosolization of SD powders; however further evaluation of the developed inhalation powders is necessary to determine their therapeutic potential for treating pulmonary tuberculosis.

Authors+Show Affiliations

New Zealand's National School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, P.O. Box 56, Dunedin 9054, New Zealand.New Zealand's National School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, P.O. Box 56, Dunedin 9054, New Zealand.New Zealand's National School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, P.O. Box 56, Dunedin 9054, New Zealand. Electronic address: Shyamal.das@otago.ac.nz.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27091294

Citation

Eedara, Basanth Babu, et al. "Phospholipid-based Pyrazinamide Spray-dried Inhalable Powders for Treating Tuberculosis." International Journal of Pharmaceutics, vol. 506, no. 1-2, 2016, pp. 174-83.
Eedara BB, Tucker IG, Das SC. Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis. Int J Pharm. 2016;506(1-2):174-83.
Eedara, B. B., Tucker, I. G., & Das, S. C. (2016). Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis. International Journal of Pharmaceutics, 506(1-2), 174-83. https://doi.org/10.1016/j.ijpharm.2016.04.038
Eedara BB, Tucker IG, Das SC. Phospholipid-based Pyrazinamide Spray-dried Inhalable Powders for Treating Tuberculosis. Int J Pharm. 2016 Jun 15;506(1-2):174-83. PubMed PMID: 27091294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis. AU - Eedara,Basanth Babu, AU - Tucker,Ian G, AU - Das,Shyamal C, Y1 - 2016/04/28/ PY - 2016/01/23/received PY - 2016/03/23/revised PY - 2016/04/15/accepted PY - 2016/4/20/entrez PY - 2016/4/20/pubmed PY - 2017/4/13/medline KW - 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) KW - Aerosolization KW - Dry powder inhalation KW - Pyrazinamide KW - Spray drying KW - Tuberculosis SP - 174 EP - 83 JF - International journal of pharmaceutics JO - Int J Pharm VL - 506 IS - 1-2 N2 - Sterilization of necrotic granulomas containing Mycobacterium tuberculosis is difficult by oral and parenteral drug delivery of antitubercular drugs. Pulmonary delivery of these drugs should increase the concentration of drug in the granulomas and, thereby, improve the sterilization. The current study aimed to develop spray-dried (SD) powders composed of pyrazinamide, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine N-(carbonyl-methoxy polyethylene glycol-2000) (DSPE-PEG2k) and l-leucine to improve drug delivery to the deeper lung. Pyrazinamide SD powders with varying amounts of DPPC (5, 15 and 25% w/w) were produced using a BUCHI B-290 Mini Spray-Dryer. The powders were characterized physicochemically and for their aerosol dispersion performance using a Next Generation Impactor (NGI). All the SD powders had a narrow particle size distribution (1.29-4.26μm) with low residual moisture (<2%). Solid state characterization confirmed that the α-polymorphic crystalline pyrazinamide transformed into the γ-polymorphic form during spray-drying. SD pyrazinamide (PDDL0) without excipients showed very poor aerosolization with a fine particle fraction (FPF%) of 8.5±1.0%. However, the SD powder with 25% w/w DPPC (PDDL3) exhibited the best aerosolization with a FPF of 73.2±4.0%. Incorporating high amounts of DPPC improved aerosolization of SD powders; however further evaluation of the developed inhalation powders is necessary to determine their therapeutic potential for treating pulmonary tuberculosis. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/27091294/Phospholipid_based_pyrazinamide_spray_dried_inhalable_powders_for_treating_tuberculosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(16)30322-2 DB - PRIME DP - Unbound Medicine ER -