Synthesis, characterization, and in vitro evaluation of polyvinyl acetate succinate vs. polyvinyl acetate phthalate as enteric-coating polymers

A new potentially useful enteric-coating agent, polyvinyl acetate succinate (PVAS), was synthesized by esterification of polyvinyl alcohol with succinic anhydride in glacial acetic acid. This polymer was compared in terms of its enteric properties with polyvinyl acetate phthalate (PVAP), the commercially available products as well as one synthesized in the laboratory under similar reaction conditions to the PVAS. Both polymers, PVAS and PVAP, were prepared using the same polyvinyl alcohol starting material. Molecular weight for the polyvinyl alcohol used was determined using intrinsic viscosity measurements. The percent phthalyl, succinyl, apparent pKa, and pH of precipitation (minimum solubility pH) were determined for these polymers as well as commercially available PVAP. In addition, other empirical constants were obtained from the slope and Y intercept of the plots of pH vs. log ((1-{dollar}alpha{dollar})/{dollar}alpha{dollar}), where {dollar}alpha{dollar} is the degree of ionization.; Infrared spectra were obtained for both polymers as well as polyvinyl alcohol, and supported their structural assignments. The pH of precipitation for the succinate polymer was lower than that of the phthalate, although the apparent pKa for the succinate polymer was higher. The succinate polymer was predicted to have a lower glass-transition temperature (Tg) than the phthalate. This was supported by differential scanning calorimetry (DSC) measurements.; Ibuprofen tablets coated with the different polymers at similar coating levels were subjected to the USP enteric dissolution test. Tablets coated with PVAS alone did not resist the acid phase test (at 37{dollar}spcirc{dollar}C) due to swelling of the PVAS film under the test conditions. However tablets coated with commercial and synthesized PVAP passed the enteric dissolution test using the full change method. A further studies to evaluate the effect of molecular weight and pKa on the enteric properties of PVAS were performed by succinoylating a higher molecular weight PVA. The pKa was also higher. Dissolution results were not significantly different. However when using PVAS in a blend with ethyl cellulose or with Hydroxypropyl methylcellulose acetate succinate HPMCAS, the coated tablets passed the enteric dissolution test. These combinations may provide the following advantages: (1) a lower Tg so that a minimum amount or no plasticizers are needed. (2) Earlier release of the drug at a lower pH may be achieved.