Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903, USA.
J Pharm Sci. 2012 Apr;101(4):1385-90. doi: 10.1002/jps.23053. Epub 2012 Jan 10.
Foam granulation is a relatively newer wet granulation process whereby foamed binder solutions are added to powders in a mixer. It is essential to understand the effect of powder substrate on foam drainage and half-life, which are relevant to nucleation and agglomeration during foam granulation. Hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) foams were characterized. Anhydrous lactose and stearic acid were selected as model soluble and insoluble substrates, respectively. The effect of these substrates on foam stability was measured by foam drainage and collapse time and microscopic observations. Both HPMC and HPC foams were similar in foam quality and foam density. Lactose destabilized both HPMC and HPC foams and foam drainage and collapse times were reduced two to four times in the presence of lactose. On the contrary, stearic acid did not significantly change foam drainage and collapse times. Microscopically, lactose exhibited rapid wetting within 15 s upon contacting the HPMC and HPC foam beds, whereas stearic acid remained unwetted even after 8 min and collapse of the foam beds. Substrate solubility can influence foam-substrate interaction. On the basis of this, we suggest potential mechanisms of nucleation and agglomeration of soluble and insoluble substrates during foam granulation.
泡沫造粒是一种相对较新的湿法制粒工艺,其中将泡沫粘结剂溶液加入到混合器中的粉末中。了解粉末基质对泡沫排水和半衰期的影响至关重要,因为这与泡沫造粒过程中的成核和团聚有关。对羟丙基甲基纤维素(HPMC)和羟丙基纤维素(HPC)泡沫进行了表征。选择无水乳糖和硬脂酸分别作为可溶性和不溶性基质的模型。通过泡沫排水和塌陷时间以及微观观察来测量这些基质对泡沫稳定性的影响。HPMC 和 HPC 泡沫在泡沫质量和泡沫密度方面均相似。乳糖使 HPMC 和 HPC 泡沫均不稳定,并且在存在乳糖的情况下,泡沫排水和塌陷时间减少了两到四倍。相反,硬脂酸对泡沫排水和塌陷时间没有明显影响。从微观上看,乳糖在与 HPMC 和 HPC 泡沫床接触的 15 秒内迅速润湿,而硬脂酸即使在 8 分钟后仍未润湿,泡沫床仍会塌陷。基质的溶解度会影响泡沫-基质相互作用。基于此,我们提出了在泡沫造粒过程中可溶性和不溶性基质成核和团聚的潜在机制。