Jones David S, Lawlor Michelle S, Woolfson A David
School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
Curr Drug Deliv. 2004 Jan;1(1):17-25. doi: 10.2174/1567201043480027.
This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.
本研究描述了一系列用于治疗牙周疾病的制剂的药物释放、流变学（动态和流动）以及质地/机械性能。这些制剂由15% w/w的聚甲基乙烯基醚-马来酸酐共聚物（PMVE-MA）、0-9% w/w的聚乙烯吡咯烷酮（PVP）组成，并含有1-5% w/w的盐酸四环素。所有制剂均表现出假塑性流动且触变性极小。依次增加PVP的浓度会使零速率粘度（由Cross模型得出）以及制剂的硬度和可压缩性（由质地剖面分析得出）增加。这些影响可能归因于聚合物缠结的增加，并且鉴于观察到的两种聚合物在质地和流变学性能方面的协同作用，还归因于PVP与PMVE-MA之间的相互作用。增加PVP的浓度会使所有制剂的储能模量和损耗模量增加，但损耗角正切减小，这表明弹性行为增加。观察到两种聚合物在粘弹性性能方面存在协同作用。与PVP浓度增加相关的粘附性增加归因于制剂生物粘附性和粘性的增加。增加药物浓度对流变学和质地性能的影响取决于PVP浓度。在较低浓度（0、3% w/w）下未观察到影响，而在存在9% w/w PVP的情况下，增加药物浓度会增加制剂的弹性、零速率粘度、硬度和可压缩性。这些观察结果归因于含有最高浓度PVP的制剂中悬浮药物的质量更大。含有6%和9% PVP（以及5% w/w药物）的制剂的药物释放延长，且为溶胀/扩散控制。基于药物释放、流变学和质地性能，建议含有15% w/w PMVE-MA、6% w/w PVP和盐酸四环素（5% w/w）的制剂可能对治疗牙周疾病有用。
