Master of Science
Patty Fu-Giles, Ph.D.
Timothy Gsell, Ph.D.
Karen D'Arcy, Ph.D.
Rifampicin is a naturally made, non-peptide antibiotic. It is bactericidal, killing by disabling the protein expression system universally conserved by all bacteria. Specifically, it inhibits the RNA polymerase protein, which is responsible for binding to a strand of DNA as a template and using it to construct a strand of mRNA. The reason rifampicin works so well is that it is a rigid molecule, and sits tightly in the pocket where it binds, allowing the bonds to be very strong. However, this also means if an amino acid with the edge of the channel with a small side chain is replaced by an amino acid with a large side chain, rifampicin may not be able to bind, simply because it cannot fit in the space. Rifampicin is mainly useful in the treatment of tuberculosis and meningococcal infections.
Coming to the pharmacokinetics of the drug, rifampicin is easily absorbed from the gastro intestinal tract. After about six hours almost the entire drug is deacetylated by esterases even in this deacytylated form rifampicin is a potent antibiotic. However, it can no longer be absorbed by the intestines and it is subsequently eliminated from the body. About 7% of the administered drug will be excreted unchanged through the urine, and urinary elimination accounts for about 30% of the dose of the drug that is excreted.
About 60% - 65% is excreted through feces. As a result of this, the drug dose has to be increased or the drug must be given at regular intervals to maintain the minimum effective concentration.
Rifampicin shows polymorphism and therefore, it is necessary to select a suitable crystal form to ensure optimum solubility and dissolution rates. An increase in amorphous content significantly reduces the dissolution rate of the powders in water. Because of the disadvantages both in physical properties and biologically rifampicin has to be synthesized in the form of nano particles which have low surface area and show good solubility and dissolution properties. Nano particles can also be designed to allow sustained drug release from the matrix. This property of nano particles enables improvement of drug bio-availability and reduction of the dosing frequency and may resolve the problem of drug resistance, which is one of the major obstacles in the control of tuberculosis epidemics.
In this method, equal amounts of PEG200 and tween 60(polysorbate 60) and calculated amount of rifampicin was dissolved in that mixture. After that, the solution was stirred with the help of high speed magnetic stirrer. After dissolving the compound completely, this solution was added to the water drop wise while the water was stirred with the magnetic stirrer. Then the nano particles are formed. If the nano particles are not formed after this procedure, homogenizer can be used. After the formation of nanoparticles, characterization using scanning electron microscope is done to confirm the surface properties of the nanoparticle.
Guttikonda, Lakshmi Sai Priyanka, "Synthesis and Characterization of Nanoparticulated Rifampicin" (2011). All Capstone Projects. 19.