Thommes Markus, Kleinebudde Peter
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
AAPS PharmSciTech. 2007 Nov 9;8(4):E95. doi: 10.1208/pt0804095.
The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.
本研究的目的是系统评估含κ-卡拉胶制剂的制粒工艺参数。该研究探讨了4个工艺参数——螺杆速度、模孔数量、摩擦板速度和滚圆机温度——对颗粒形状、尺寸、尺寸分布、拉伸强度和药物释放等颗粒性质的影响。这些参数在2(4)全因子设计中系统地变化。此外，在恒定工艺条件下研究了4种药物——非那西丁、氯霉素、茶苯海明和盐酸利多卡因。通过使用大量模孔和高滚圆机速度，以高产率获得了最接近球形的颗粒。所研究的工艺参数对尺寸分布、机械稳定性和药物释放没有相关影响。难溶性药物非那西丁和氯霉素制成的颗粒具有合适的形状、尺寸和拉伸强度，且药物释放迅速。茶苯海明和利多卡因的盐类，以pH 3的水溶液作为制粒液时，会影响颗粒形状、机械稳定性和药物释放性能。对于茶苯海明，这归因于与κ-卡拉胶的离子相互作用，导致溶解过程中形成稳定的基质且不会崩解。利多卡因的作用与钠离子的作用相当，钠离子会抑制卡拉胶的胶凝作用，导致颗粒具有快速崩解和药物释放特性。颗粒性质受工艺参数和所用活性药物成分的影响。
