ArticlePharmaceutics2024
Effects of Different Weak Small Organic Acids on Clofazimine Solubility in Aqueous Media.
Article in Pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Quality-by-Design Development of a Clofazimine-Pyrazinamide Dermal Emulsion and Its Diffusion Behavior in Strat-MPharmaceuticals (Basel, Switzerland) · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
BACKGROUND/
objectivesClofazimine (CFZ) is a Biopharmaceutics Classification System (BCS) II drug introduced in the US market in 1986 for the treatment of leprosy. However, CFZ was later withdrawn from the market due to its extremely low aqueous solubility and low absorption. In the literature, the intrinsic solubility of CFZ has been estimated to be <0.01 μg/mL, and solubilities of its different salt forms in simulated gastric and intestinal fluids are <10 µg/mL. These are extremely low solubilities for the dissolution of a drug administered orally at 100-200 mg doses.
methodsIn the present investigation, seven weak organic acids (adipic, citric, glutaric, maleic, malic, succinic, and tartaric) were tested by determining the aqueous solubility of CFZ as the function of acid concentration to investigate whether any of the acids would lead to the supersolubilization of CFZ.
resultsThere were only minimal increases in solubilities when concentrations of acids in water were increased up to 2.4 M. The solubilities, however, increased to 0.32, 1.23, and 10.68 mg/mL, respectively, in 5 M solutions of tartaric, malic, and glutaric acids after equilibration for 24 h at 25 °C. Crystalline solids were formed after the equilibration of CFZ with all acids. Apparently, salts or cocrystals were formed with all acids, except for glutaric acid, as their melting endotherms in DSC scans were in the range of 207.6 to 248.5 °C, which were close to that of CFZ itself (224.8 °C). In contrast, the adduct formed with glutaric acid melted at the low temperature of 77 °C, and no other peak was observed at a higher temperature, indicating that the material converted to an amorphous state.
conclusionsThe increase in CFZ solubility to >10 mg/mL in the presence of 5 M glutaric acid could be called supersolubilization when compared to the intrinsic solubility of the basic drug. Such an increase in CFZ solubility and the conversion of the glutarate adduct to an amorphous state are being exploited to develop rapidly dissolving dosage forms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.