Alur H H, Pather S I, Mitra A K, Johnston T P
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Katz Pharmacy Building, Room 211A, 5100 Rockhill Road, Kansas City 64110-2499, USA.
Int J Pharm. 1999 Oct 15;188(1):1-10. doi: 10.1016/s0378-5173(99)00211-2.
The objective of this study was to evaluate the gum from Hakea gibbosa (Hakea) as a sustained-release and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits. Flat-faced core tablets containing either 22 or 32 mg of Hakea and 40 or 25 mg of chlorpheniramine maleate (CPM) per tablet with either sodium bicarbonate or tartaric acid in a 1:1.5 molar ratio were formulated using a direct compression technique and were coated with Cutina(R) on all but one face. The resulting plasma CPM concentration versus time profiles were determined following buccal application of the tablets in rabbits. The strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time. Following the application of the mucoadhesive buccal tablets, the following values for several pharmacokinetic parameters were obtained. The force of detachment for the mucoadhesive buccal tablets containing 22 mg of Hakea and either 25 and 40 mg CPM, and 32 mg Hakea and 40 mg CPM increased from 1.64+/-0.47 to 7.32+/-0.34 N, 1.67+/-0.30 to 7.21+/-0.36 N, and 2.93+/-0.73 to 7.92+/-0.60 N, respectively from 5 to 90 min following application to excised intestinal mucosa. Addition of either sodium bicarbonate or tartaric acid, as well as higher amounts of CPM, did not affect the mucoadhesive bond strength. These results demonstrate that the novel, natural gum, H. gibbosa, may not only be used to sustain the release of CPM from a unidirectional-release buccal tablet, but also demonstrate that the tablets are sufficiently mucoadhesive for clinical application. The mucoadhesive strength as measured by the force of detachment, can be modulated by altering the amount of Hakea in the tablet. The mucoadhesive buccal tablets evaluated represent an improved transbuccal delivery system for conventional drug substances.
本研究的目的是评估哈克木属植物（Hakea gibbosa，哈克木）的树胶作为颊含片的缓释和黏膜黏附成分在兔颊黏膜上的应用效果。采用直接压片技术制备每片含22或32毫克哈克木以及40或25毫克马来酸氯苯那敏（CPM）且含有摩尔比为1:1.5的碳酸氢钠或酒石酸的平面片芯，并除一面外其余各面均包被Cutina®。在兔颊部给药后测定所得血浆CPM浓度随时间的变化曲线。片剂的黏膜黏附强度也根据剥离力随时间的变化进行定量。应用黏膜黏附颊含片后，获得了几个药代动力学参数的以下值。含22毫克哈克木以及25毫克和40毫克CPM的黏膜黏附颊含片，以及含32毫克哈克木和40毫克CPM的黏膜黏附颊含片，在应用于离体肠黏膜后5至90分钟内，其剥离力分别从1.64±0.47牛增加到7.32±0.34牛、从1.67±0.30牛增加到7.21±0.36牛、从2.93±0.73牛增加到7.92±0.60牛。添加碳酸氢钠或酒石酸以及更高量的CPM均不影响黏膜黏附结合强度。这些结果表明，新型天然树胶哈克木不仅可用于维持CPM从单向释放颊含片中的释放，而且还表明该片剂具有足够的黏膜黏附性可用于临床应用。通过剥离力测量的黏膜黏附强度可通过改变片剂中哈克木的量来调节。所评估的黏膜黏附颊含片代表了一种用于传统药物的改进型经颊给药系统。
