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Evaluating Particle Size Differences of Suspension-Based Nasal Sprays Through In Vitro and Pharmacokinetic Approaches

Hochhaus G, Amini E, Berger S, Shur J, Kurumaddali A, Schilling U, Jiao Y, Drescher SK, Seay B, Baumstein SM, Abu-Hasan MN, Oguntimein O, Carrasco C, Winner L, Delvadia RR, Saluja B, Price R, Conti DS, Dhapare S, Newman B, Bulitta JB.

Respiratory Drug Delivery 2022. Volume , 2022: 47-54.

Abstract:

Food and Drug Administration (FDA) currently recommends a weight of evidence approach for demonstration of bioequivalence (BE) of suspension-based nasal sprays and aerosols, which consists of in vitro, pharmacokinetic (PK) and comparative clinical endpoint BE studies. Recent product-specific guidances (PSGs) for such products also recommend alternative pathways to comparative clinical endpoint BE studies using validated advanced methodologies for assessing the particle size distribution (PSD) of suspended drug particles within the product. This presentation compared the ability of PK studies to detect differences in the PSD with two in vitro methodologies, morphologically directed Raman spectroscopy (MDRS) and in vitro dissolution tests. Two mometasone furoate (MF) nasal sprays, differing in their PSD were formulated and characterized through in vitro and PK methods. PK studies indicated significantly larger AUC (area under the concentration-time curve) estimates for the formulation comprised of smaller MF particles. These results correlated well with the dissolution tests, indicating that faster dissolution of smaller particles likely resulted in less efficient removal of nasally deposited MF particles through mucociliary clearance. In summary, PK studies and in vitro approaches, including the assessment of the dissolution rate, may potentially be used as an alternative BE approach to comparative clinical endpoint BE studies.