Adeyeye C M, Price J C
Department of Pharmaceutical Chemistry and Pharmaceutics, School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania 15282.
Pharm Res. 1994 Apr;11(4):575-9. doi: 10.1023/a:1018931002991.
A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.
采用使用微型篮的改良美国药典桨法，研究了各种制剂对布洛芬微球体外溶出的影响。含有石蜡或微晶蜡等蜡且无改性剂的制剂表现出非常缓慢的溶出曲线和不完全释放，增加药物载量或制备更小的微球并不能改善这种情况。添加硬脂醇和单硬脂酸甘油酯等改性剂大大提高了溶出速率，20%（w/w）接近可预测溶出的最佳比例。更高的药物载量和更小的微球尺寸提高了含改性剂微球的溶出速率。最佳制剂包含微晶蜡或微晶蜡以及作为改性剂的硬脂醇，药物含量为17%。包封分散剂浓度的增加对溶出曲线影响很小。来自窄粒度级分微球的溶出数据表明为球形基质药物释放动力学；50%溶出时间随微球直径的平方而降低。对于具有与布洛芬相似溶解度特征的药物，使用适当的改性剂，蜡微球制剂可为可预测的缓释剂型提供起始基础。
