Enteric polymers have been long used in oral drug delivery. They have been viewed as "pH-dependent" in the sense of utilizing the pH gradient along the intestine to target drug release to different intestinal segments based on the polymer's dissolution pH threshold, with the dosage form delivering the drug to the most proximal segment where the pH value exceeds that dissolution threshold. However, it has been overlooked that it is the surface pH that directly controls an enteric polymer's dissolution rate, and that this surface pH is not a function of solely the bulk pH. In this study, we investigated the effects of bulk pH and bicarbonate molarity (bicarbonate being the buffering species in the intestinal fluid in vivo) on the performance of different enteric-coated (EC) products utilizing various polymers. Our results showed that an enteric polymer's dissolution rate (and so its surface pH) is more strongly affected by bicarbonate molarity ([HCO3-]) than by bulk pH, with [HCO3-] seeming to be the intestinal fluid parameter limiting the in vivo performance of these polymers. This is because of the effective pKa of bicarbonate in the diffusion layer surrounding the dissolving polymer being lower than the value of ~6.1 (at physiological temperature and ionic strength) commonly encountered in literature. This is attributed to the interconversion between carbonic acid and carbon dioxide not being sufficiently rapid to maintain equilbrium in this layer under ordinary hydrodynamic conditions. These findings shed a new light on reports concerning the failure of various EC products to deliver drugs to the intestinal segments they are supposed to target. In addition, these results pose the question whether referring to enteric polymers as pH-dependent or bicarbonate molarity-dependent (with a [HCO3-] gradient also existing along the intestine) would be more practical from a pharmaceutical development point of view.

pH-Dependent dissolution of enteric polymers: A misconception? Implications for pH-dependent drug delivery

2019 Spring National Meeting

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