Li Weiyong, Cunningham John, Rasmussen Henrik, Winstead Denita
Analytical Development, Johnson & Johnson Pharmaceutical Research & Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA.
J Pharm Sci. 2007 Dec;96(12):3470-7. doi: 10.1002/jps.20974.
Potency and content uniformity of granulation and tablet samples are usually determined by HPLC or UV-VIS. However, these methods are not suitable for the determinations of other important process related attributes. The monitoring of nucleation, granule growth and granule breakage in the granulation process requires different analytical tools. In early formulation development of a new active pharmaceutical ingredient (API), out of trend content uniformity results were observed for batches manufactured using a fluid bed wet granulation process. A qualitative near infrared (NIR) method was used to characterize the process samples, which were separated into fractions with sieve sizes of 40, 60, 80, 100, and 200-mesh. Based on spectral analysis, the method was able to demonstrate changes in relative content of lactose, microcrystalline cellulose and the API at different processing times. The results also showed that the out of trend content uniformity was caused by large particle size of the API. Because lactose and microcrystalline cellulose are commonly used ingredients in wet granulation formulations, the qualitative NIR method may find wide applications.
颗粒剂和片剂样品的效价和含量均匀度通常通过高效液相色谱法（HPLC）或紫外可见分光光度法（UV-VIS）来测定。然而，这些方法并不适用于测定其他与工艺相关的重要属性。制粒过程中晶核形成、颗粒生长和颗粒破碎的监测需要不同的分析工具。在一种新的活性药物成分（API）的早期制剂开发过程中，观察到使用流化床湿法制粒工艺生产的批次出现了超出趋势的含量均匀度结果。采用定性近红外（NIR）方法对工艺样品进行表征，这些样品被分离成筛目尺寸为40、60、80、100和200目的级分。基于光谱分析，该方法能够证明在不同加工时间乳糖、微晶纤维素和API的相对含量变化。结果还表明，超出趋势的含量均匀度是由API的大粒径引起的。由于乳糖和微晶纤维素是湿法制粒制剂中常用的成分，定性近红外方法可能会有广泛的应用。
