TY - JOUR
T1 - Promising chitosan-alginate combination for rifampicin dry powder inhaler to target active and latent tuberculosis
AU - Putri, Kurnia Sari Setio
AU - Ramadhani, Laily Syahri
AU - Rachel, Theodora
AU - Suhariyono, Gatot
AU - Surini, Silvia
N1 - Funding Information:
The authors would like to acknowledge Universitas Indonesia for funding this research through the “Publikasi Terindeks Internasional (PUTI) Q3 Universitas Indonesia” grant with Contract no. NKB-1812/UN2.RST/HKP.05.00/2020. The authors also would like to thank Dr. Wouter L. J. Hinrichs (University of Groningen, The Netherlands) for his professional advice on the DPI.
Publisher Copyright:
© 2022. Kurnia Sari Setio Putri et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
PY - 2022/5
Y1 - 2022/5
N2 - A suitable excipient with certain characteristics is required in formulating a dry powder inhaler (DPI), to deliver the anti-tuberculosis (TB) drug into the lung and provide adequate drug concentration in the lung and in the alveolar macrophage, to overcome active and latent TB infection. This study aimed to explore the combination of chitosan and alginate in formulating rifampicin DPI. Rifampicin DPI was prepared by spray drying using various combinations of chitosan and alginate. The obtained rifampicin dry powder was characterized for its particle size distribution, morphology, moisture content, drug content, and entrapment efficiency. In addition to the dissolution study in a phosphate buffer of pH 7.4 with sodium lauryl sulfate 0.05% and in a phthalate buffer of pH 4.5, the cytotoxicity study toward cell line A549 was also conducted. The combination of chitosan and alginate in DPI F3 (RIF-Ch-Alg 2:1:1) provides a suitable drug release profile of rifampicin DPI in both simulated lung fluid (78.301% ± 1.332% in 2 hours) and simulated macrophage fluid (41.355% ± 1.259% in 2 hours). DPI F3 also possessed an aerodynamic particle size of 11.4288 ± 1.259 µm and was also considered safe toward pulmonary epithelial cells (viability 89.73%) in concentrations up to 0.1 mg/ml. In conclusion, combination of chitosan and alginate is a prospective carrier to develop dry powder inhaler with suitable characteristics for tuberculosis therapy.
AB - A suitable excipient with certain characteristics is required in formulating a dry powder inhaler (DPI), to deliver the anti-tuberculosis (TB) drug into the lung and provide adequate drug concentration in the lung and in the alveolar macrophage, to overcome active and latent TB infection. This study aimed to explore the combination of chitosan and alginate in formulating rifampicin DPI. Rifampicin DPI was prepared by spray drying using various combinations of chitosan and alginate. The obtained rifampicin dry powder was characterized for its particle size distribution, morphology, moisture content, drug content, and entrapment efficiency. In addition to the dissolution study in a phosphate buffer of pH 7.4 with sodium lauryl sulfate 0.05% and in a phthalate buffer of pH 4.5, the cytotoxicity study toward cell line A549 was also conducted. The combination of chitosan and alginate in DPI F3 (RIF-Ch-Alg 2:1:1) provides a suitable drug release profile of rifampicin DPI in both simulated lung fluid (78.301% ± 1.332% in 2 hours) and simulated macrophage fluid (41.355% ± 1.259% in 2 hours). DPI F3 also possessed an aerodynamic particle size of 11.4288 ± 1.259 µm and was also considered safe toward pulmonary epithelial cells (viability 89.73%) in concentrations up to 0.1 mg/ml. In conclusion, combination of chitosan and alginate is a prospective carrier to develop dry powder inhaler with suitable characteristics for tuberculosis therapy.
KW - alginate
KW - chitosan
KW - cytotoxicity
KW - drug release profile
KW - dry powder inhaler
KW - Rifampicin
UR - http://www.scopus.com/inward/record.url?scp=85129942511&partnerID=8YFLogxK
U2 - 10.7324/JAPS.2022.120507
DO - 10.7324/JAPS.2022.120507
M3 - Article
AN - SCOPUS:85129942511
SN - 2231-3354
VL - 12
SP - 98
EP - 103
JO - Journal of Applied Pharmaceutical Science
JF - Journal of Applied Pharmaceutical Science
IS - 5
ER -