Alvarez-Lorenzo C, Gómez-Amoza J L, Martínez-Pacheco R, Souto C, Concheiro A
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15706, Santiago de Compostela, Spain.
Int J Pharm. 1999 Mar 25;180(1):91-103. doi: 10.1016/s0378-5173(98)00409-8.
This study investigated the influence of the rheological properties of hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties (mean molecular weight between 5x105 and 1.2x106, nominal viscosity between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion coefficients at 37 degrees C ranged from 3.5x10-7 to 1.1x10-3 cm2/min, and were in all cases markedly higher than those predicted on the basis of gel macroviscosity as determined by capillary viscometry. In general, the theophylline diffusion coefficient declined exponentially with HPC concentration; in the case of the lowest-molecular-weight HPC, however, the diffusion coefficient remained constant to HPC concentrations of up to 0.8%, probably because of the high entanglement concentration of the HPC. Gel microviscosities as determined by dynamic light scattering (DLS) with latex microspheres (162 nm diameter) were considerably lower than the macroviscosities determined by capillary viscometry, and similar to microviscosities estimated on the basis of theophylline diffusion. Nevertheless, macroviscosity was correlated with microviscosity, suggesting that it is of value for approximate estimates of rates of diffusion of theophylline from HPC gels.
本研究考察了羟丙基纤维素（HPC）凝胶的流变学性质对凝胶中0.2 g/l茶碱体外释放的影响。使用六种HPC品种（平均分子量在5×10⁵至1.2×10⁶之间，标称粘度在100至4000 mPa·s之间），浓度为0 - 2%（w/w）进行实验。37℃时茶碱的扩散系数范围为3.5×10⁻⁷至1.1×10⁻³ cm²/min，在所有情况下均明显高于基于毛细管粘度测定法所确定的凝胶宏观粘度预测值。一般来说，茶碱扩散系数随HPC浓度呈指数下降；然而，对于最低分子量的HPC，扩散系数在HPC浓度高达0.8%时保持恒定，这可能是由于HPC的高缠结浓度所致。通过动态光散射（DLS）使用乳胶微球（直径162 nm）测定的凝胶微观粘度明显低于通过毛细管粘度测定法测定的宏观粘度，且与基于茶碱扩散估算的微观粘度相似。尽管如此，宏观粘度与微观粘度相关，这表明其对于近似估计茶碱从HPC凝胶中的扩散速率具有价值。
