Prodrug is the precursor of drug which is made by derivatization of the same to enhance the bioavailability by pharmacokinetics, lipid solubility by partition coefficient and increase the physicochemical and biochemical parameters by pharmacodynamics. All two prodrugs showed different logP values and molecular weights according to the solubility parameters and electronegativity: logP profile: Prodrug-B>Prodrug-A; molecular weight profile: Prodrug-B>Prodrug-A. The main side effect of NSAID is gastric acidity due to release of free H+ because all NSAIDs have free-COOH (carboxylic acid) group which act by competitive inhibition of cyclooxygenase enzyme (COX1/COX2). Here the target of this project has been designed in such a way to convert the free –COOH/–OH of API (aspirin/paracetamol) into prodrug of two ester (–COO–) and one amide (– CONH–) linkage (Prodrug-A) and one ester and two amide linkage (Prodrug-B) which releases free API after metabolic hydrolysis in acidic pH: 1-4 and alkaline pH: 7-9. Since the prodrugs are repository forms so chances to release gastric acid has been minimized due to non-availability of free-COOH group in stomach. The biotransformation of active drug from prodrug takes such a time in stomach that all goes upto duodenum and then ileum of small intestine that chances of acidity is reduced. Finally all prodrugs go to small intestine where alkaline pH starts so gastric acidity is reduced. Since all two prodrugs are made of two NSAID: Prodrug-A (logP=2.15) releases Aspirin and Paracetamol, Prodrug-B (logP=3.94) releases Indomethacin and Paracetamol which shows distinct two Rt values in HPLC both in acidic an alkaline hydrolysis and these Rt values of Prodrugs match with the individual API components so the purpose of our goal has been completed successfully. The pH of gastric acid varies from 1.5- 3.5 in the human stomach lumen, the acidity being maintained by the proton pump H+/K+ ATPase. So the pattern for acid hydrolysis was adjusted at pH=3- 3.5 by HCl. The pH of intestine varies from 5.6-6.9, so the pattern for alkaline hydrolysis was adjusted at pH=7.0-8.0 by NaOH. In case of codrug which is made by non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals interactions and π-interactions between two APIs, so the release of parent molecule will be faster than prodrug both in acidic as well as in alkaline pH because prodrug is made by covalent bonding between two APIs. log P profile: Codrug-B (3.42)>Codrug-A (1.55); molecular weight profile: Codrug-B (508.94g)>Codrug-A (331.31g).
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