Schoenwald R D, Ward R L, DeSantis L M, Roehrs R E
J Pharm Sci. 1978 Sep;67(9):1280-3. doi: 10.1002/jps.2600670923.
Gel formulations containing 2% pilocarpine hydrochloride were prepared from ethylene maleic anhydride, carbomer, hydroxyethylcellulose, polyacrylamide, ethylhydroxyethylcellulose, hydroxypropylcellulose, and poly(methylvinyl ether--maleic anhydride). The viscosity characteristics of each formulation were evaluated from rheograms developed at 37 degrees using a cone and plate viscometer. Single-point viscosities were determined at room temperature using a single-point rotational viscometer. Plastic viscosity parameters correlated to miosis durations in the rabbit following ophthalmic dosing of 50 microliters. Carbomer formulations varying in concentration between 0.9 and 5.0% (w/w) showed a discontinuous relationship when either yield value or plastic viscosity was plotted against miosis durations. At carbomer concentrations above 3%, miosis durations increased 1.5-fold. Above and below this range, plastic parameters did not correlate to miosis duration. It was reasoned that the increased duration was a consequence of the gel's increased yield value such that appreciable in vivo thinning of the gel does not take place with eyelid and/or eyeball movements. As a result, the residence time of the drug in the eye would be expected to increase, thus promoting an increased duration.
含有2%盐酸毛果芸香碱的凝胶制剂由乙烯马来酸酐、卡波姆、羟乙基纤维素、聚丙烯酰胺、乙基羟乙基纤维素、羟丙基纤维素和聚（甲基乙烯基醚-马来酸酐）制备而成。使用锥板粘度计在37℃下绘制流变图来评估每种制剂的粘度特性。使用单点旋转粘度计在室温下测定单点粘度。在兔眼给药50微升后，塑性粘度参数与缩瞳持续时间相关。当将屈服值或塑性粘度与缩瞳持续时间作图时，浓度在0.9%至5.0%（w/w）之间变化的卡波姆制剂呈现出不连续的关系。在卡波姆浓度高于3%时，缩瞳持续时间增加了1.5倍。在此范围之上和之下，塑性参数与缩瞳持续时间不相关。据推测，持续时间增加是凝胶屈服值增加的结果，使得凝胶在体内不会因眼睑和/或眼球运动而明显变薄。因此，预计药物在眼中的停留时间会增加，从而延长持续时间。
