Evaluation of the effect of some Eudragits on dissolution of Celecoxib solid dispersion formulations

Abstract

Background: Many drug candidates have poor bioavailability as a result of low water solubility. Therefor developing appropriate formulation for these drugs in order to increase their water solubility and bioavailability is of a great importance. Objective: The aim of this study is first, to identify the effectiveness of some polymers in inhibition of celecoxib (CX) precipitation from solution. Second, to investigate on the influence of the effective inhibitor polymers on dissolution behavior of CX from solid dispersion (SD). Method: The effectiveness of Eudragits (Eu) E100, S100, L100, L100-55, RL and RS and PVP in inhibition of drug precipitation were evaluated. Solid-dispersion formulations (1:1) were used to improve the dissolution rate of drug. The effective inhibitor excipients (Eu L100 and PVP) were added to inhibit the drug precipitation. Solid dispersions were produced by solvent evaporation. Furthermore, they were characterized by FT-IR and differential scanning calorimetry (DSC). Results: The results indicated that Eu E100, Eu L100, Eu S100 and PVP inhibited CX precipitation from solution efficiently, probably owing to their interaction with CX. For Eu E, Eu L100, Eu S100 and PVP SDs, a similar degree of supersaturation was generated via dissolution and it was maintained up to end of test, suggesting that inhibition effect of polymer on drug governs the longevity of the supersaturated solution formed by dissolution of SDs. Among the excipients investigated, Eu L100-55 had the most efficiency in generating the supersaturated solution of CX. However, this excipient failed to prevent the rapid precipitation of CX from solution formed by dissolution of SDs. Nevertheless, adding an efficient precipitation inhibitor (Eu L100) to CX:Eu L100-55 formulation did not allow the CX precipitate rapidly out of the solution and maintained the supersaturation state of it. Conclusion: According to the results, adding Eu L100 to CX:Eu L100-55 formulation could promote the dissolution behavior, stability and probably bioavailability of CX.