9/28/2023 0 Comments Laser diffraction spectroscopyIn line with the Generic Drug User Fee Amendments (GDUFA) program and the “weight-of-evidence” approach, the FDA has published a number of product-specific guidances (PSGs) for a series of nasal products. Thus, the US Food and Drug Administration (FDA) relies on cumulative evidence of indirect measures to establish BE.įor an abbreviated new drug application (ANDA) submitted under section 505(j) of the Federal Food, Drug, and Cosmetic Act, the FDA recommends a “weight-of-evidence” approach to help determine BE between test and reference products for locally acting nasal suspensions as presented in Fig. Complex drug-device combination products such as those seen for nasal suspensions further compound this by being dependent on formulation/device, patient/device, manufacturing, and processing factors. However, the determination of BE for locally acting drugs has been a long standing challenge in the pharmaceutical industry as the absorption of the API at the local site of action is typically difficult to analyze directly, and there is no guarantee that local drug concentration is at equilibrium with the systemic distribution. To demonstrate bioequivalence (BE) with its reference listed drug (RLD), a generic product must demonstrate an absence of a significant difference in the rate and extent of absorption of the active pharmaceutical ingredient (API) when administered at the same molar dose under similar experimental conditions, either single dose or multiple dose. The correlation observed between PSD and dissolution rate extends the use of dissolution as a critical analytical tool demonstrating BE between test and reference products. This approach has been approved for use in lieu of a comparative clinical endpoint BE study. For suspension-based nasal products, MDRS allows the measurement of API PSD which is critical for BE assessment. Dissolution analysis confirmed the trend observed by MDRS in terms of PSD. Although the PSD between distinct techniques cannot be directly compared due to inherent differences between these methodologies, the same trend is observed for three out of the four batches. A systematic approach was utilized to develop a robust method for the analysis of the PSD of MFM in Nasonex® and four test formulations containing the MFM API with different particle size specifications. Upon formulation manufacture, the droplet size, single actuation content, spray pattern, plume geometry, the API dissolution rate, and the API PSD by MDRS were determined. The PSD of the MFM batches was characterized before formulation manufacture using laser diffraction and automated imaging. Nasal suspension formulations containing different PSD of mometasone furoate monohydrate (MFM) were manufactured. Dissolution was also investigated as an orthogonal technique. This study investigated the utility of the morphologically-directed Raman spectroscopy (MDRS) method to investigate the particle size distribution (PSD) of nasal suspensions. Analytical tools are required to determine the particle size of the active pharmaceutical ingredient (API) and the structure of a relatively complex formulation. Particle & Particle Systems Characterization Wiley Demonstrating bioequivalence (BE) of nasal suspension sprays is a challenging task. Simulations and experiments with reticles verified the need for this adaptation technique and its efficiency when applied. ![]() Based on these results, particles were considered to be ellipsoids with specific (but negligible) surface structures and a mathematical adaptation method was developed by extending the evaluation theory from spheres to randomly in space oriented ellipsoids. its axis ratio, affects the measurement result greatly and must be taken into account in the evaluation method. In contrast to this advantageous outcome, the particle's microstructure, i.e. its surface roughness, has almost no or only a negligible effect on the measurement result. The detailed investigations showed that the particle's microstructure, i.e. To determine the influence of the particle shape, measurements of arbitrarily shaped particles were simulated, evaluated and compared with results for spherical particles of the same projected area. ![]() As this evaluation theory is limited to spheres only, the measurement of irregularly shaped particles results in errors in the evaluated particle size distribution. The evaluation algorithm employed in laser diffraction spectroscopy is usually based on the Fraunhofer diffraction theory for spheres. Laser Diffraction Spectroscopy: Influence of Particle Shape and a Shape Adaptation Technique Laser Diffraction Spectroscopy: Influence of Particle Shape and a Shape Adaptation Technique
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