Evaluation of the Inhibitory potential of Polymers on Carvedilol Precipitation from the Supersaturated Solutions

Abstract

Introduction: Due to their sensitivity to pH changes, poorly soluble alkaline drugs such as Carvedilol tend to precipitate quickly after entering the intestinal environment after dissolving in the acidic environment of the stomach, which causes low and variable bioavailability of these types of drugs. Aim: Our goals were to evaluate the potential of precipitation inhibition of Carvedilol in the presence of polymers.Methods: Five polymers: PVP, HPMC, HPC, PVA and PEG had been chosen at different molecular weight. Precipitates were characterized by differential scanning calorimetry and FT-IR to investigate the possible drug-polymer interactions.Results: The rank order of polymers based on their efficiency of precipitation inhibition in solution was found to be HPC followed by HPMC, PVP and PVA.PEG was found to be ineffective Carvedilol precipitation inhibition polymer. In the presence of efficient polymers, the FT-IR spectra and DSC thermograms of the precipitates showed absorption band and melting peak shifts, respectively, indicating the possible drug-polymer molecular interactions which plays a significant role in precipitation inhibition of drug.Conclusion: This study manifested the importance of physicochemical properties of polymers to inhibit drug precipitation. On the other hand, it could be seen how the change in molecular weight and polymer concentration can affect drug precipitation. It is important to determine the effect order of polymers in stabilizing the supersaturated state of the drug. This study provided information about the rank order of the polymers based on their effectiveness in precipitation inhibition of Carvedilol, which is valuable in the rational selection of polymers for formulation development of Carvedilol. This case, in turn, can increase the absorption and reduce the changes in drug absorption in the case of poorly soluble drugs.