Planinsek O, Pisek R, Trojak A, Srcic S
University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000, Ljubljana, Slovenia.
Int J Pharm. 2000 Oct 10;207(1-2):77-88. doi: 10.1016/s0378-5173(00)00535-4.
Surface free energy was determined for model substances pentoxyfilline, acyclovir, lactose and binding agents (that were used in the granulation process) hydroxypropilmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) were determined by contact angle measurements. The methods of Wu, Good-van Oss and Della Volpe were used for solid-surface free-energy calculation. Spreading coefficients (S) were calculated and correlated with granulate properties. Granulates consisted of model drug and binding agent, and were produced in fluid bed granulator Glatt powder coater granulator GPCG1 by means of spraying the colloidal solution of binder on the model substance. Granules contained either 5% or 10% binder. Inverse granules, however, were also produced by spraying the model drug (i.e. pentoxyfilline and lactose) on the binding agent (HPMC, PVP). Particle size distribution, friability, true density, bulk density and tapped density of the granulates were determined. Although many different parameters influence the granule properties, it has been found that the interactions between the drug and the binder play a very important role. Spreading coefficients were found to be in good correlation with the friability of granulates. Positive spreading coefficient values of the binder over the model substance correlate well with the low friability of the granules containing lower amount of binder, i.e. 5%. In the group of the same binder, the spreading coefficient values decrease from pentoxyfilline over lactose to acyclovir. Friability results show that, for the system under consideration, PVP offers certain advantages over the grade of HPMC employed. The increase of the binder amount from 5 to 10% resulted in more friable granulates. Lower work of cohesion of the binder (PVP and HPMC) than the work of adhesion between binder and the model substances is considered responsible for the higher friability of the granules. The inverse granulation process, where the suspension of the model substance was sprayed over the solid binder particles, proved more efficient with HPMC than with PVP. According to the spreading coefficient results, the binder should spread over the drug. However, the kinetics of wetting appears to play an important role in the granulation process. According to these results, the conclusion was made that water wets HPMC much faster than PVP.
通过接触角测量法测定了模型物质己酮可可碱、阿昔洛韦、乳糖以及制粒过程中使用的粘合剂（羟丙基甲基纤维素（HPMC）和聚乙烯吡咯烷酮（PVP））的表面自由能。采用吴法、古德-范奥斯法和德拉沃尔佩法进行固体表面自由能计算。计算了铺展系数（S）并将其与颗粒性质相关联。颗粒由模型药物和粘合剂组成，通过将粘合剂的胶体溶液喷洒在模型物质上，在流化床制粒机格拉特粉末包衣机GPCG1中制备而成。颗粒中粘合剂的含量为5%或10%。然而，反向制粒是通过将模型药物（即己酮可可碱和乳糖）喷洒在粘合剂（HPMC、PVP）上进行的。测定了颗粒的粒度分布、脆碎度、真密度、堆密度和振实密度。尽管许多不同参数会影响颗粒性质，但已发现药物与粘合剂之间的相互作用起着非常重要的作用。发现铺展系数与颗粒的脆碎度具有良好的相关性。粘合剂在模型物质上的正铺展系数值与含有较低粘合剂含量（即5%）的颗粒的低脆碎度密切相关。在同一粘合剂组中，铺展系数值从己酮可可碱到乳糖再到阿昔洛韦逐渐降低。脆碎度结果表明，对于所研究的体系，PVP相对于所使用的HPMC等级具有一定优势。粘合剂用量从5%增加到10%会导致颗粒更易碎。粘合剂（PVP和HPMC）的内聚功低于粘合剂与模型物质之间的粘附功被认为是颗粒脆碎度较高的原因。将模型物质的悬浮液喷洒在固体粘合剂颗粒上的反向制粒过程，结果表明HPMC比PVP更有效。根据铺展系数结果，粘合剂应铺展在药物上。然而，润湿动力学似乎在制粒过程中起着重要作用。根据这些结果得出结论，水对HPMC的润湿速度比PVP快得多。
