Siegel R A, Johannes I, Hunt C A, Firestone B A
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Pharm Res. 1992 Jan;9(1):76-81. doi: 10.1023/a:1018983828027.
The swelling kinetics of polybasic gels consisting of copolymers of methyl methacrylate and dimethylaminoethyl methacrylate are studied in solutions at various acidic pH values, with monoacidic derivatives of acetic acid added as buffers. The effects of solution pH, as well as buffer pKa and concentration, on swelling rate are assessed. Gel swelling rate shows a nearly linear dependence on the concentration of nonionized buffer in the solution, as determined by the Henderson-Hasselbach equation. This result is explained in terms of the increased availability of protons that are carried by the nonionized buffer to bare amines on the gel. In fact, the so-called pH sensitivity of these gels, under these conditions, can be attributed mainly to the effect of pH on the nonionized buffer concentration. A practical consequence is that these gels may not reliably mediate pH-sensitive swelling-controlled release in oral applications, since the levels of buffer acids in the stomach (where swelling and release are expected to occur) generally cannot be controlled. However, the gels may be useful as mediators of pH-triggered release when precise rate control is of secondary importance.
研究了由甲基丙烯酸甲酯和甲基丙烯酸二甲氨基乙酯的共聚物组成的多元凝胶在不同酸性pH值溶液中的溶胀动力学,并添加单酸性乙酸衍生物作为缓冲剂。评估了溶液pH值以及缓冲剂的pKa和浓度对溶胀速率的影响。根据亨德森-哈塞尔巴赫方程,凝胶溶胀速率与溶液中非离子化缓冲剂的浓度呈现近似线性关系。这一结果可解释为非离子化缓冲剂携带的质子更容易与凝胶上的游离胺结合。实际上,在这些条件下,这些凝胶所谓的pH敏感性主要可归因于pH对非离子化缓冲剂浓度的影响。一个实际的结果是,由于胃部(预期会发生溶胀和释放)的缓冲酸水平通常无法控制,这些凝胶在口服应用中可能无法可靠地介导pH敏感的溶胀控制释放。然而,当精确的速率控制次要时,这些凝胶可能用作pH触发释放的介质。