Hydrolytic stability of diltiazem in the presence of chosen polymers - Poloxamer 407 and Ammonio Metacrylate Copolymer Type B (Eudragit RS): а preliminary study

Introduction : The hydrolytic stability of the calcium channel blocker representative diltiazem hydrochloride in the presence of different polymeric entourage was quantitatively assessed using HPLC. Aim: The experiment was performed in order to establish drug-excipients compatibility in Poloxamer 407 hydrogel formulations, where the drug was introduced either by a direct (conventional) approach or in the form of Eudragit RS microsponge -type particles with sustained drug release. Materials and Methods : Samples of conventional diltiazem 2% hydrogel and microsponge -enriched diltiazem 2% hydrogel were stored at 25±2 o C for 10 months, protected from light. Analysis of the chemical decomposition rate of diltiazem hydrochloride to its desacetyl degradant - O - desacetyl - diltiazem hydrochloride - was performed in the period between 4 th and 10 th month of storage. Results and Discussion: It was hypothesized that a polymeric “shield” of Eudragit RS in the composition of diltiazem -loaded porous microspheres and/or the enhanced viscosity achieved by the addition of high-molecular gelling agent Poloxamer 407 to an aqueous drug dispersion will benefit the drug’s stability. Instead, a negative effect on the hydrolysis rate was found to be dominant for both polymers, likely due to an “unfavorable” shift in the dielectric conductivity of the media and/or suspected catalytic effect of quaternary ammonium groups of Eudragit RS . Conclusion : These preliminary results led us to a deeper understanding of the polymeric impact on diltiazem hydrolytic behavior and a very useful foundation for a future preformulation stage in the development of diltiazem modified-release semisolid forms for the treatment of chronic anal fissure.