IP 142 LECTURE Matibag, Maychelle Anne Matienzo, Jeff Drug Complexes Complexation affects either the biopharmaceutical or pharmaceutical

properties, sometimes to an advantage and sometimes, adversely. Here are some examples how complex formation affects such properties (listed in order of drug-complexing agent): chemical stability (such as benzocaine-caffeine) o inhibits reactions (usually oxidations) which are catalyzed by metal ions solubility (such as aspirin-caffeine) o masking of taste (more preferred as an ingredient for chewable tablets) o gives some drug the extensive-release property (due to slow dissolution) o some dissolve faster due to complex formation (thus bioavailability is greater) absorption rate (such as salycylamide-caffeine) production of incompatibilities and unwanted complexation reactions (such as widely used polyethers forming precipitates with H-bond donors from phenols and carboxylic acids); and, partition coefficient (such as benzoic acid-caffeine; or salicylamide-caffeine) For example, salicylamide and caffeine form a complex in aqueous solution which has an apparent lipoid-aqueous partition coefficient intermediate between the partition coefficients of free salicylamide and free caffeine. The observations suggest that the complex can be transferred as such and that diffusion of the drugs through the bulk solution to the membrane surface is not transfer-rate limiting. A theoretical analysis of the simultaneous equilibria involved in the partitioning between an organic and an aqueous phase of two interacting drugs in the presence of one another shows that the apparent partition coefficient of a drug complex does not necessarily represent the ratio of transfer rate constants of the complex itself across the interface. There will always be a correlation between the apparent partition coefficient and the intestinal transfer rate constant of drug complexes. The effect of complex formation on drug absorption correlates with kinetic analyses based on the stability or binding constants of the respective complexes, the difference in diffusivity between free drug and drug complex, and the absorption rate of the free drug. The absorption rate of drugs can be modified by formation of complexes which differ from the free drug mainly in size or in lipoid-water partition coefficient. Reference: Gennaro, A. R., 2000. Remington: The Science and Practice of Pharmacy. 20th ed. MD: Lippincott Williams and Wilkins. p. 195. Sinko, P. J., 2006. Martins Physical Pharmacy and Pharmaceutical Sciences. 5th ed. MD: Lippincott Williams and Wilkins. pp.272-273. Reuning, R. H, Levy, G.,2006. Effect of complex formation on drug absorption VIII. Intestinal transfer characteristics of the salicylamide-caffeine system. Available at http://onlinelibrary.wiley.com/doi/10.1002/jps.2600570813/abstract?systemMessage=Due+to+ scheduled+maintenance%2C+access+to+Online+Library+will+be+disrupted+on+Saturday%2C+5t h+Feb+%2711+between+10%3A00-12%3A00+GMT [Accessed 2 February 2011]. 7th of February, 2011