Design and synthesis of ionic liquid formulation of NSAID (Non Stereoidal Anti̇ Inflamatory Drugs ) as a quaternary ammonium salts

Design and synthesis of pharmaceutical salts are one of the prime aspects of drug development as 50% of drugs are in salt form. Pharmaceutical salts are occur with combination of an active ion and inert counterion. Exchanging the inert counterion of an active pharmaceutical salt with a pharmaceutically active ion can change the phyisco-chemical properties such as melting point, solubility and also the pharmaceutical properties e.g bioavailability, stability and permeability. The biggest problem of giving the pharmaceutical salts is polymorphism and this is one of the principal matters of obstructing the drug administration. This problem can be eliminated by administration of the drugs in ionic liquid form. One of the solutions for this is the pharmaceutical salts of which both anions and cations are active drug material. Moreover, personalized drug design which shows both antimicrobic and analgesic features only in one drug is one of the active research fields of drug industry at the present days. The aim of this study is to design and synthesize pharmaceutical salts of which anions are active drug ingredients, changing the drug properties e.g.solubility, permeability and length of effect and to synthesize new chiral quaternary ammonium salts which has antimicrobial activity. In this study, secondary and tertiary amines and QAS's synthesis have been performed via controlled alkylation of rasemic and chiral α-phenylethylamine; the structure of dialkyl phenylethyl methyl ammonium iodide have been changed via alkyl chain lenght and branched alkyl groups. In the second stage, the in vitro antimicrobial activities of the QASs' rasemic and chiral forms, have been tested by disc diffusion method according to rules of N.C.C.L.S( the National Committee for Clinical Laboratory Standards) against to the American Type Culture Collection (Maryland, USA): Escherichia coli, Staphylococcus aureus, Streptecocus pyogenes, Pseudomonas aeruginosa, Bacillus subtilis and a kind of fungus, Candida albicans. Finally, dual biologically active pharmaceutical salts have been synthesized by metastasis reactions of high-effective antimicrobial QASs and NSAID (Non-Stereoidal Anti Inflammatory Drug) like ibuprofenate and naproxenate.