Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia.
Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia.
Int J Pharm. 2024 Oct 25;664:124653. doi: 10.1016/j.ijpharm.2024.124653. Epub 2024 Aug 30.
Evaluation of the particle size distribution (PSD) of active pharmaceutical ingredients (APIs) in nasal suspension products is challenging due to the presence of both API and excipients. To characterize these intricate formulations, it is essential to have sophisticated analytical methods that offer high spatial resolution and the ability to chemically pinpoint and map out the presence of API particles. However, such advanced techniques have not been documented for nasal formulations yet. In this proof-of-concept study, we investigated the utility of optical photothermal infrared spectroscopy (O-PTIR) to analyze the PSD of commercially available Nasonex® and its generic Azonaire® nasal mometasone furoate (MM) suspensions. Simultaneous O-PTIR and Raman spectra, as well as IR chemical maps, were collected from the particles in both formulations. Spatially resolved spectra from the particles confirmed the presence of peaks related to MM (1727 cm, 1661 cm, and 1122 cm) and excipient microcrystalline cellulose (MCC) (1061 cm). The PSD of MM particles was characterized using chemical maps specific to MM (1661 cm) and automated imaging. Results confirmed that the PSD of both formulations were comparable. Spectral analysis also revealed the presence of free MM, free MCC, and particles containing co-localized MM and MCC. For suspension-based nasal products, O-PTIR enables the measurement of API PSD, which is critical for formulators in developing nasal suspension products. This approach holds potential as an innovative complimentary analytical tool that could diminish the need for extensive clinical endpoint bioequivalence studies when evaluating the comparability of generic and brand-name nasal suspension products.
评估鼻用混悬剂产品中原料药（API）的粒度分布（PSD）具有挑战性，因为存在 API 和赋形剂。为了对这些复杂的制剂进行表征，必须使用具有高空间分辨率且能够对 API 颗粒进行化学定位和绘图的复杂分析方法。然而，这种先进的技术尚未用于鼻用制剂。在这项概念验证研究中，我们研究了光热红外光谱（O-PTIR）在分析市售 Nasonex®及其通用 Azonaire®鼻腔糠酸莫米松（MM）混悬剂的 PSD 方面的适用性。从这两种制剂中的颗粒同时收集 O-PTIR 和拉曼光谱以及红外化学图谱。来自颗粒的空间分辨光谱证实存在与 MM（1727 cm、1661 cm 和 1122 cm）和赋形剂微晶纤维素（MCC）（1061 cm）相关的峰。使用针对 MM（1661 cm）和自动成像的化学图来表征 MM 颗粒的 PSD。结果证实，两种制剂的 PSD 具有可比性。光谱分析还揭示了游离 MM、游离 MCC 以及含有 MM 和 MCC 共定位的颗粒的存在。对于基于混悬剂的鼻用产品，O-PTIR 能够测量 API 的 PSD，这对于开发鼻用混悬剂产品的制剂师来说至关重要。这种方法具有作为一种创新的补充分析工具的潜力，可以减少在评估通用和品牌名鼻用混悬剂产品的可比性时对广泛的临床终点生物等效性研究的需求。
