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Compatibility investigation for a new antituberculotic fixed dose combination with an adequate drug delivery
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- The compatibility of formulation components is crucial for safe and high-quality medicines. To detect the potential for incompatibility and to assess formulation stability, it is beneficial to conduct a compatibility study during the drug development phase. The therapy of tuberculosis normally consists of two or more medicines taken together. Consequently, different antituberculotic fixed-dose combination (FDC) formulations have been developed. Isoniazid is first-line medicine and present in several FDCs. Low bioavailability due to the active substances’ incompatibility in acidic medium was reported for some of these FDC forms. Rifabutin, also a first- line antituberculotic, is available in the market as a single component formulation. This study presents compatibility testing of these two active substances for a new FDC and evaluates the impact of the most common solid dosage forms’ excipients on the stability of two active substances. The potential for interaction between the formulation components was analyzed by the UHPLC method. One degradation product and one interaction product were observed and further characterized by high- resolution mass spectrometry. Still, significant degradation of two active substances, such as reported in marketed FDC formulations was not detected for this combination. The stability and drug delivery of the proposed combination were confirmed by the dissolution test in acidic medium.
- Subjects :
- Pharmacology
Materials science
Rifabutin
Organic Chemistry
Fixed-dose combination
Biological Availability
Pharmaceutical Science
02 engineering and technology
021001 nanoscience & nanotechnology
030226 pharmacology & pharmacy
Formulation stability
Drug Combinations
03 medical and health sciences
0302 clinical medicine
Drug Discovery
Compatibility (mechanics)
Drug delivery
compatibility
FDC
isoniazid
rifabutin
impurities
characterization
MS/MS
dissolution
Isoniazid
medicine
Humans
Tuberculosis
0210 nano-technology
medicine.drug
Biomedical engineering
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6cd5ca48b66f78d41c248e7811a5d080
- Full Text :
- https://doi.org/10.6084/m9.figshare.12601135