Investigating the effects of amphipathic gastrointestinal compounds on the solution behaviour of salt and free base forms of clofazimine: An in vitro evaluation

International Journal of Pharmaceutics
Pauric BanniganSarah P Hudson

Abstract

Interactions between hydrophobic drugs and endogenous gastrointestinal substances have the potential to manipulate drug concentration in the human gastrointestinal system, and thus likely play an important role in determining the rate of absorption for hydrophobic drugs. The effects of phospholipids, bile salts and digestive proteins on the solution behaviour of clofazimine in biorelevant media was demonstrated here using dissolution experiments and solid state analytical techniques. Clofazimine is a hydrophobic, anti-mycobacterial agent with virtually no detectable water solubility in its free base form. Salt forms of the drug offer improved aqueous solubility but are unstable in solutions at low pH (pH 1.6) or high pH (pH 6.5). At low pH and high chloride ion concentrations, CFZ in solution experiences a high driving force to crystallize from solution as a hydrochloride salt, which is insoluble, while at high pH CFZ does not dissolve to any extent. In this study, it is demonstrated that amphipathic compounds present in the gastric and intestinal systems can overcome the instability experienced by CFZ at these pH values. This is done by encapsulation of the hydrophobic drug in mixed bile salt phospholipid micelles in both the ...Continue Reading

Citations

Mar 21, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·James FlynnSarah P Hudson
Nov 23, 2018·Journal of Colloid and Interface Science·James FlynnSarah P Hudson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.