Development and Validation of New Analytical Method for Determination of Particle Size Distribution in Alogliptin Benzoate Drug Substance Using Laser-based Particle Size Analyzer
Jitendra Kumar Dubey *
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Jitendra Koundinya
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Babul Nishad
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Praveen Choubay
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Nirav Parekh
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Mehul Gujrati
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Pankaj T. Shah
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
Frenil Vaidya
CTX Lifesciences Pvt. Ltd., Analytical Research & Development, Sachin, Surat, Gujarat 394230, India.
*Author to whom correspondence should be addressed.
Abstract
Particle size distribution (PSD) characterisation is important for pharmaceutical drug-substance quality because particle size can influence formulation-related performance. This study developed and validated a wet-dispersion laser-diffraction method for determining the PSD of Alogliptin Benzoate using the Malvern Mastersizer 3000 (Ultra Plus). Methanol, chloroform, and liquid paraffin light were evaluated during method development, and liquid paraffin light was selected as the dispersion medium. The optimised measurement conditions included a particle refractive index of 1.50, dispersant refractive index of 1.468, sample absorption value of 1.0, obscuration of 10–20%, stirrer speed of 2000 rpm, and sonication for 45 seconds. Method performance was assessed using Dᵥ10, Dᵥ50, and Dᵥ90 through precision, intermediate precision, and robustness studies. Method precision produced %RSD values of 3.00%, 2.47%, and 3.91% for D(0.1), D(0.5), and D(0.9), respectively. Intermediate precision gave corresponding %RSD values of 3.46%, 3.40%, and 8.77%. The cumulative %RSD values for method and intermediate precision were 3.21%, 3.30%, and 6.80%, respectively. Robustness was evaluated by deliberate changes in stirrer speed, obscuration range, and sonication time, with the reported results remaining within the stated acceptance criteria. The developed procedure therefore demonstrated consistent performance under the conditions evaluated and is suitable for routine particle size determination of Alogliptin Benzoate drug substance in quality control laboratories.
Keywords: Alogliptin benzoate, drug substance, particle size distribution, wet dispersion, Malvern Mastersizer 3000, method validation, robustness