AbstractLocally-acting orally inhaled and nasal drug products (OINDP) are complex dosage forms which depend on a combination of device, patient, and formulation. Its localised effect inside the human body adds further intricacies when developing a generic drug product. To facilitate the development of locally-acting topical products, the US Food and Drug Administration (FDA) proposed the concept of Q3 microstructural equivalence, suggesting that any differences for products with qualitative (Q1) and quantitative (Q2) sameness can be related to the arrangement of matter and/or its state of aggregation. This study investigates the introduction of this concept to OINDPs by evaluating and validating several scientifically robust techniques that can be used to characterise the microstructures of OINDPs.
The use of a newly developed technique, morphologically-directed Raman spectroscopy (MDRS), and dissolution to characterise the in situ particle size distribution (PSD) of complex nasal drug products was studied by tracking the PSD of the drug substance before and after formulation. These two techniques were sensitive to differences in PSD of the drug substance in the final product and may be used in an orthogonal approach to demonstrate equivalence of the drug substance PSD in the final product.
For orally inhaled drug products, an aerosol dose collection (ADC) apparatus able to capture the aerosolised dose onto a filter was developed, validated, and used to evaluate microstructural differences by dissolution and MDRS. These techniques were able to capture differences in the microstructure of products Q1 equivalent and Q2 dissimilar, but also between products Q1 and Q2 equivalent although sourced from different regions.
In vitro release testing with a novel immersion cell apparatus and rheology were also used to characterise differences between locally-acting nasal drug products with a distinct concentration of a thickening agent.
This work highlights that the concept of Q3 microstructural equivalence may be applied to the development of OINDPs with scientifically robust and validated techniques.
|Date of Award||8 Sep 2021|
|Supervisor||Ian Blagbrough (Supervisor), Robert Price (Supervisor), Paul De Bank (Supervisor) & Jag Shur (Supervisor)|