Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation

May, Sabine; Jensen, Birte; Wolkenhauer, Markus; Schneider, Marc; Lehr, Claus‐Michael

doi:10.1007/s11095-012-0744-2

Cited by 78 publications

(68 citation statements)

References 13 publications

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“…Causality between rate of dissolution and the clinical performance of an OIP is complex, but differences in dissolution rate between different OIP's with otherwise similar aerosol performance (with potential effects on local and systemic bioavailability, and drug safety) have been demonstrated in several recent publications (11,25,(35)(36)(37)(38). A variety of dissolution test methods have been developed (35)(36)(37)(38)(39)(40)(41), and it is generally accepted that these methods may have value, even if they are not strictly in vivo predictive, by discriminating between formulations with similar aerodynamic properties but different release properties.…”

Section: Dissolution Permeation Particle Clearance and Tissue Expomentioning

confidence: 99%

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

Forbes

Bäckman

Christopher

et al. 2015

AAPS J

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Abstract. This article is part of a series of reports from the "Orlando Inhalation Conference-Approaches in International Regulation" which was held in March 2014, and coorganized by the University of Florida and the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of the conference was to foster the exchange of ideas and knowledge across the global scientific and regulatory community in order to identify and help move towards strategies for internationally harmonized, science-based regulatory approaches for the development and marketing approval of inhalation medicines, including innovator and second entry products. This article provides an integrated perspective of case studies and discussion related to in vitro testing of orally inhaled products, including in vitro-in vivo correlations and requirements for in vitro data and statistical analysis that support quality or bioequivalence for regulatory applications.

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Section: Dissolution Permeation Particle Clearance and Tissue Expomentioning

confidence: 99%

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

Forbes

Bäckman

Christopher

et al. 2015

AAPS J

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“…Several dissolution techniques for powders for inhalation have been described, such as the flow-through cell (7)(8)(9), the Franz diffusion cell (8)(9)(10), and the paddle apparatus equipped with a special sample holder (8,11,12). The common disadvantage of these apparatus is the nonphysiologically large amount of dissolution medium (60-1000 mL).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the deposition of particles with an aerodynamic diameter less than 5 µm was carefully controlled. This deposition process allowed an exact quantification of the amount on the membrane, which is crucial for the dissolution process (8,11). In consequence, we could specifically test several variables to identify critical factors, especially membrane material, addition of dissolution medium on the membrane (air side), and stirring of the acceptor medium, respectively.…”

Section: Introductionmentioning

confidence: 99%

Miniature In Vitro Dissolution Testing of Powders for Inhalation

May¹,

Kind²,

Jensen³

et al. 2015

Dissolution Technol.

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The aim of this study was the development and evaluation of a miniaturized setup for in vitro dissolution testing of inhalation powders based on an adapted Transwell system with artificial membranes. Such a system should be able to discriminate between different inhalation powders with good reproducibility by allowing easy handling while only small amounts of test compound and liquids are necessary.The modified Transwell setup was tested by depositing a fraction of aerosol particles with an aerodynamic particle size less than 5 µm on different artificial membranes (inserts) using a modified abbreviated Andersen cascade impactor to guarantee homogeneous and non-agglomerated particle distribution, which is essential for dissolution testing of powders for inhalation. The performance of the system was tested with the commercially available Transwell inserts and artificial membranes in a modified setup. Both systems provided reliable and comparable data that extends the flexibility of the test system with respect to the commercial setup. The dissolution tests were performed using budesonide and a proprietary active pharmaceutical ingredient (API), substance A, from the Boehringer Ingelheim research line. Besides the use of different membranes, the setup was modified to allow stirring, which improved the reproducibility of the dissolution process. Surprisingly, providing additional dissolution medium in the donor compartment for the poorly soluble substances decreased the stability of the dissolution process. Furthermore, the membrane material had a strong influence on the dissolution profile. The polyester (PE) and polycarbonate (PC) membranes interacted with the substances used, whereas regenerated cellulose and Isopore PC membranes were more suitable for the dissolution testing of these APIs.

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“…The USP Inhalation Ad Hoc Advisory Panel "could not find compelling evidence suggesting that such dissolution testing is kinetically and/or clinically crucial for currently approved inhalation drug products (19). " Some proposals about dissolution testing of inhalation products using the paddle apparatus, flow-through cell, Franz diffusion cell apparatus, and Transwell diffusion apparatus were published (20)(21)(22)(23).…”

Section: In Vitro Performance Testingmentioning

confidence: 99%