Dr Rajendra Gode College of Pharmacy, Department of Pharmaceutics, Malkapur, Buldhana (M.S.) 443 101, India.
Sekkei Bio Pvt. Ltd, Novel Formulation Development Laboratory, Bangalore, Karnataka 560 065, India.
J AOAC Int. 2024 Jul 4;107(4):558-570. doi: 10.1093/jaoacint/qsae033.
Estimation of the drug and development of the method is a critical aspect of formulation development and a critical factor for analytical scientists. Gefitinib is a poorly soluble anticancer drug.
The present research focuses on the topic of the development of innovative quality by design methods for the estimation of gefitinib (GF) from bulk, pharmaceutical tablet formulation, and complex nanoformulations.
To simplify the estimation of poorly soluble drugs such as GF, response surface methodology (RSM) was adopted with effective leverages to obtain precise computation design space using the Box-Behnken design (BBD) model. The major three mixed-effect independent factors (percentage of buffer, pH of buffer, and flow rate) were screened with three prominent dependent responses (viz., theoretical plate, retention time, and tailing factor) selected for optimal analysis. Furthermore, co-processed steps were employed for the estimation of the analyte from the complex formulation.
The RP-HPLC method uses the quality by design (QbD) approach can effectively estimate the analyte concentration of less than 4.5 min. The developed method was economically robust and sensitive and shows a relative standard deviation (RSD, %) of less than 2% for all the selected validation parameters. The estimated design space suggests the highest desirability (R2-0.998) at 60% of buffer in the mobile phase, pH 4.25, and flow rate of 0.7 mL/min.
The QbD approach was used to design and develop the method by understanding the interaction between dependent and independent variables to get the optimum values. The developed method was validated successfully and can be useful for formulation scientists to estimate drug concentration and drug release profiles from complex nanoformulations.
The analytical approach was designed and quantified using a quality-by-design approach to make the RP-HPLC method more robust and efficient for the estimation of analytes from complex nanoformulations. The method is also useful to eliminate the interfering molecule during estimation by employing co-processing steps. The developed method saves time and cost of solvent and employs QbD as a requirement of recent regulatory concern.
药物评估和方法开发是制剂开发的关键环节，也是分析科学家的关键因素。吉非替尼是一种难溶性抗癌药物。
本研究专注于通过创新质量设计方法来开发吉非替尼（GF）的估算，这些方法适用于原料药、药物片剂制剂和复杂纳米制剂。
为了简化对难溶性药物如 GF 的估算，采用响应面法（RSM），利用 Box-Behnken 设计（BBD）模型的有效杠杆作用，获得精确的计算设计空间。主要的三个混合效应独立因素（缓冲液的百分比、缓冲液的 pH 值和流速）与三个突出的依赖响应（即理论塔板数、保留时间和拖尾因子）一起进行筛选，以选择最佳分析。此外，还采用共处理步骤来估算复杂制剂中的分析物。
反相高效液相色谱法（RP-HPLC）方法采用质量源于设计（QbD）方法可以有效地估算少于 4.5 分钟的分析物浓度。所开发的方法具有经济稳健性和灵敏度，对于所有选定的验证参数，相对标准偏差（RSD，%）均小于 2%。估计的设计空间表明，在流动相中有 60%的缓冲液、pH 值为 4.25 和流速为 0.7 mL/min 的情况下，具有最高的理想度（R2-0.998）。
采用质量源于设计（QbD）方法来设计和开发方法，通过了解依赖变量和独立变量之间的相互作用，获得最佳值。所开发的方法已成功验证，可用于制剂科学家估算复杂纳米制剂中的药物浓度和药物释放曲线。
采用质量设计方法设计和定量分析方法，使 RP-HPLC 方法更稳健、高效，可用于从复杂纳米制剂中估算分析物。该方法还可用于通过采用共处理步骤在估算时消除干扰分子。所开发的方法节省了溶剂的时间和成本，并采用 QbD 作为当前监管关注的要求。
