Popo Manuel, Romero-Torres Saly, Conde Carlos, Romañach Rodolfo J
University of Puerto Rico, Mayaguez Campus, Department of Chemistry, PO Box 9019, Mayaguez, PR 00680, USA.
AAPS PharmSciTech. 2002;3(3):E24. doi: 10.1208/pt030324.
A near infrared spectroscopic method was developed to determine drug content in a 20% (wt/wt) ibuprofen and spray-dried hydrous lactose blend. A blending profile was obtained after blending for 0.5, 1, 3, 5, 10, and 20 minutes. Stream sampling was used to collect about 20 blend samples at each of the blending times from a laboratory scale V-blender. The samples collected were used to develop a near infrared calibration model. The calibration model was then used to determine the drug content of unknown samples from 2 validation blends. The validation blends were not included in the calibration model; they were used to evaluate the effectiveness of the calibration model. A total of 45 samples from the 2 validation blends were predicted by the near infrared calibration model and then analyzed by a validated UV spectrophotometric method. The root mean square error of prediction for the first validation blend was 5.69 mg/g and 3.30 mg/g for the samples from the second blend. A paired t test at the 95% confidence level did not indicate any differences between the drug content predicted by the near infrared spectroscopy (NIRS) method and the validated UV method for the 2 blends. The results show that the NIRS method could be developed while the blending profile is generated and used to thoroughly characterize a new formulation during development by analyzing a large number of samples. The new formulation could be transferred to a manufacturing plant with an NIRS method to facilitate blend uniformity analysis.
开发了一种近红外光谱法，用于测定含20%（重量/重量）布洛芬和喷雾干燥含水乳糖混合物中的药物含量。混合0.5、1、3、5、10和20分钟后获得混合曲线。采用流样法在实验室规模的V型混合器中，在每个混合时间收集约20个混合样品。所收集的样品用于建立近红外校准模型。然后使用该校准模型来测定来自2个验证混合物的未知样品的药物含量。验证混合物未包含在校准模型中；它们用于评估校准模型的有效性。近红外校准模型对来自2个验证混合物的总共45个样品进行了预测，然后通过经过验证的紫外分光光度法进行分析。第一个验证混合物的预测均方根误差为5.69 mg/g，第二个混合物样品的预测均方根误差为3.30 mg/g。在95%置信水平下的配对t检验表明，近红外光谱（NIRS）法预测的药物含量与2个混合物的经过验证的紫外法之间没有任何差异。结果表明，可以在生成混合曲线的同时开发NIRS方法，并通过分析大量样品用于在开发过程中全面表征新制剂。可以使用NIRS方法将新制剂转移到生产工厂，以促进混合均匀性分析。
