Solubility enhancement of Cefpodoxime acid by aqueous solution of paracetamol through acoustical, polarizable continuum model and antimicrobial activity studies

The pharmacological response of an antibiotic depends on the optimum concentration of homogenous solution of the drug and deviation from this may result in major problems with generic and formulation developments of new chemical entities (NCE's). Further, the introduction of additional new drugs with greater pharmacokinetic activity is limited because of their poor aqueous solubility. In the present work, an attempt has been made to explore the enhancement of solubility and hence the bioavailability or antimicrobial activity of a pharmaceutically significant drug Cefpodoxime acid (CA), a metabolite of third generation cephalosporin antibiotic cefpodoxime proxetil (CP), by the addition of aqueous paracetamol (PA) solution. Ultrasonic investigation has been carried out on the aqueous solutions of PA containing different concentration of CA at ambient and physiological temperatures and at pressure 101.3 kPa. The measured values of ultrasonic velocity, density and dynamic viscosity and the computed acoustical parameters at 303.15 K, 310.15 K and 313.15 K reveal significant intermolecular interactions between unlike drug molecules. The polarizable continuum model (PCM) study for the two drugs in four different solvents is applied in the calculation of free energy of solution (Delta Gsol) which provide valid information regarding the mutual solubility of the two drugs and possible enhancement of bioavailability of CA in presence of PA. Antimicrobial activity of CA in the presence of PA in aqueous medium confirms the improvisation of solubility of CA drug. The data obtained through antimicrobial activity studies support the increased pharmacokinetic activity of CA in the presence of PA in aqueous environment.