Highly increasing solubility of clofazimine, an extremely water-insoluble basic drug, in lipid-based SEDDS using digestion products of long-chain lipids
Loading...
Author (Corporation)
Publication date
06.2025
Typ of student thesis
Course of study
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Journal of Pharmaceutical Sciences
Special issue
DOI of the original publication
Link
Series
Series number
Volume
114
Issue / Number
6
Pages / Duration
103782
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
Clofazimine (CFZ) is a highly effective antibiotic against leprosy and drug-resistant tuberculosis and is on the WHO List of Essential Drugs. However, no CFZ product with optimal bioavailability is available worldwide. The manufacturer withdrew its only marketed product, presumably due to poor and erratic bioavailability because of extremely low aqueous solubility in the gastrointestinal pH range. We developed a self-emulsifying drug delivery system (SEDDS) using a lipid digestion product (LDP) containing glyceryl monooleate and oleic acid at ∼1:2 molar ratio to increase drug solubility and ensure rapid dispersion into microemulsion. While solubilities of CFZ in glyceryl monooleate, glyceryl trioleate, and two common surfactants (Tween 80 and Kolliphor EL) were comparatively low (<15 mg/g), oleic acid provided a very high solubility of ∼500 mg/g. Because of the presence of oleic acid, the clofazimine solubility in SEDDS containing a 50:50 w/w mixture of LDP and surfactants increased to 130 mg/g. Two formulations having 50 or 100 mg CFZ in one gram of SEDDS were developed. They dispersed rapidly and almost completely in simulated intestinal fluid and in the USP pH 6.8 phosphate buffer containing 3 mM sodium taurocholate. There was some precipitation of CFZ as the HCl salt at low gastric pH during dispersion testing, but the effect could be avoided using enteric-coated capsules. Thus, an enteric-coated lipid-based formulation for CFZ with as high as 100 mg/g drug loading was developed, providing complete drug release and producing microemulsions under intestinal pH conditions.
Keywords
Clofazimine, SEDDS, Lipid digestion product, Oleic acid, Glyceryl monooleate, Solubility, Drug loading, Enteric coating, Quantum-chemical simulation, Dispersion test
Subject (DDC)
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
0022-3549
1460-2415
1460-2415
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Closed
License
Citation
Kandagatla, H. P., Kathawala, M. H., Syed, A., Verbić, T. Ž., Avdeef, A., Kuentz, M., & Serajuddin, A. T. M. (2025). Highly increasing solubility of clofazimine, an extremely water-insoluble basic drug, in lipid-based SEDDS using digestion products of long-chain lipids. Journal of Pharmaceutical Sciences, 114(6), 103782. https://doi.org/10.1016/j.xphs.2025.103782