Abstract
To overcome some of the shortfalls of the types of dissolution testing currently used for pulmonary products, a new custom-built dissolution apparatus has been developed. For inhalation products, the main in vitro characterisation required by pharmacopoeias is the deposition of the active pharmaceutical ingredient in an impactor to estimate the dose delivered to the target site, i.e., the lung. Hence, the collection of the respirable dose (<5 µm) also appears to be an essential requirement for the study of the dissolution rate of particles, because it results as being a relevant parameter for the pharmacological action of the powder. In this sense, dissolution studies could become a complementary test to the routine testing of inhaled formulation delivered dose and aerodynamic performance, providing a set of data significant for product quality, efficacy and/or equivalence. In order to achieve the above-mentioned objectives, an innovative dissolution apparatus (RespiCell™) suitable for the dissolution of the respirable fraction of API deposited on the filter of a fast screening impactor (FSI) (but also of the entire formulation if desirable) was designed at the University of Parma and tested. The purpose of the present work was to use the RespiCell dissolution apparatus to compare and discriminate the dissolution behaviour after aerosolisation of various APIs characterised by different physico-chemical properties (hydrophilic/lipophilic) and formulation strategies (excipients, mixing technology).
Highlights
The study of the solid state of the active pharmaceutical ingredient (API), of its modification induced by the processing and of the resulting dissolution properties is fundamental for the development of innovative lung products, as well as for the development of bioequivalent drugs
These new techniques, once validated and implemented, have to produce robust data to complement traditional aerosolisation performance studies that seem inadequate for the challenges posed by the rapidly changing landscape of the inhalation product market
The RespiCell dissolution apparatus has been designed with the aim of having a system able to offer a liquid-air interface for the dissolution and a reduced receiver volume compared to that of the dissolution apparatuses using vessels, such as those adapted from USP
Summary
The in vitro dissolution tests for solid oral dosage forms are well-established characterisation steps necessary to guide formulation and product development as well as to ensure quality control during medicinal product manufacture This has never been the case for inhalation drug products, as the first and most critical step for their clinical performance involves the delivery of the active pharmaceutical ingredient (API) from the device and its deposition in the nose or lung [1,2]. The respiratory drug delivery market is moving from low-dose locally acting drugs to higher-dosage, poorly soluble and possibly systemically acting compounds [6] For this generation of inhalation products, it appears that the classic pharmacopeial characterisations are no longer appropriate to exhaustively describe the product profile, and the development of more bio-relevant techniques would help to predict the products’ biological availability [7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
