Fassihi A R, Munday D L
Department of Pharmacy, University of the Witwatersrand, Medical School, Johannesburg, South Africa.
J Pharm Pharmacol. 1989 Jun;41(6):369-72. doi: 10.1111/j.2042-7158.1989.tb06479.x.
The dissolution of an experimental formulation of film-coated slow release theophylline mini-tablets has been investigated using the USP paddle apparatus in test media at pH 1.2 (hydrochloric acid), pH 5.4 and 7.4 (phosphate buffers) at 37 degrees C. Monitoring of in-vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in less than 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in-vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasize the usefulness of an animal model for assessment of in-vivo drug release and subsequent absorption, during the development of modified release dosage forms.
采用美国药典桨法装置，在37℃下于pH 1.2（盐酸）、pH 5.4和pH 7.4（磷酸盐缓冲液）的试验介质中，对薄膜包衣缓释茶碱微型片的一种实验制剂的溶出度进行了研究。在相同的流体动力学条件下，监测体外茶碱12小时的释放情况，结果表明，pH 1.2时的溶出速率明显更快（不到10小时内释放了95%的总药物含量），高于在磷酸盐缓冲液中的溶出速率。在pH 5.4和pH 7.4时，12小时后的最大释放量分别约为片剂总药物含量的20%和30%。然而，给兔子口服该片剂后的体内生物利用度相当于总药物的95%以上，与静脉注射相同剂量相比。在磷酸盐缓冲液中体外溶出过程中药物释放延迟归因于片剂片芯-包衣界面处磷酸根离子与茶碱分子之间可能的相互作用。这些发现表明，从缓释包衣微型片中释放茶碱的速率和程度对磷酸盐缓冲液高度敏感。这些数据还强调了在开发缓释剂型过程中，动物模型对于评估体内药物释放及随后吸收的有用性。
