In-vitro Evaluation of Solution Pressurised Metered Dose Inhaler Sprays with Low-GWP Propellants.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-02-12 DOI:10.1007/s11095-025-03830-6

Daniel J Duke, Lingzhe Rao, Benjamin Myatt, Phil Cocks, Stephen Stein, Nirmal Marasini, Hui Xin Ong, Paul Young

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引用次数: 0

Abstract

Purpose: The transition from high Global Warming Potential (GWP) propellants such as HFA134a to low-GWP alternatives such as HFA152a and HFO1234ze(E) in pressurised metered dose inhalers (pMDIs) poses a number of challenges for inhaled pharmaceutical product development. Changes in chemicophysical properties will alter product performance, impacting in-vitro bioequivalence metrics. This study investigates those differences using equivalent pMDI hardware and formulations.

Methods: Aerodynamic particle size distribution (APSD) measurements, laser diffraction and high-speed imaging were used to compare the performance of HFA134a, HFA152a and HFO1234ze(E) solution formulations of beclomethasone dipropionate. Propellant-only placebos, cosolvent-free solutions, and ethanol solutions at 8% and 15% w/w were investigated.

Results: HFA152a formulations had increased drug deposition on the actuator and throat while HFO1234ze(E) produced comparable APSD performance to HFA134a formulations. Plumes from HFA152a formulations spread more rapidly and were less stable and repeatable than those from HFA134a. HFO1234ze(E) plumes spread more slowly than HFA134a, but converged with HFA134a ex-mouthpiece. Differences between propellants were moderated by the addition of ethanol.

Conclusion: Plume stability is a driver of differences between formulations in the near-orifice region. Shot-to-shot repeatability differences are more pronounced ex-mouthpiece, where mixing with ambient air is dominant. Modifications to low-GWP pMDI product actuator orifice and mouthpiece geometries may provide a route to improved in-vitro product bioequivalence relative to current pMDIs. Differences between formulations are modest and may be managed through a combination of formulation, orifice and mouthpiece geometry changes. These generic formulations provide a database of benchmark data against which the performance of low-GWP products may be compared.

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.