Logotyp: till Uppsala universitets webbplats

Impactor-type dose deposition is a common prerequisite for dissolution testing of inhaled medicines, and drug release typically takes place through a membrane. The purpose of this work is to develop a mechanistic model for such combined dissolution and release processes, focusing on a drug that initially is present in solid form. Our starting points are the Noyes-Whitney (or Nernst-Brunner) equation and Fick's law. A detailed mechanistic analysis of the drug release process is provided, and approximate closed-form expressions for the amount of the drug that remains in solid form and the amount of the drug that has been released are derived. Comparisons with numerical data demonstrated the accuracy of the approximate expressions. Comparisons with experimental release data from literature demonstrated that the model can be used to establish rate-controlling release mechanisms. In conclusion, the model constitutes a valuable tool for the analysis of in vitro dissolution data for inhaled drugs.

Dissolution rate impacts the absorption rate of poorly soluble inhaled drugs. In vitro dissolution tests that can capture the impact of changes in critical quality attributes of the drug product on in vivo dissolution are important for the development of products containing poorly soluble drugs, as well as modified release formulations. In this study, an extended mathematical model allowing for dissolution of polydisperse powders and subsequent diffusion of dissolved drug across a membrane is described. In vitro dissolution profiles of budesonide, fluticasone propionate, and beclomethasone dipropionate delivered from three commercial drug products were determined using a membrane-type Transwell dissolution test, which consists of a donor and an acceptor compartment separated by a membrane. Subsequently, the profiles were analyzed using the developed mechanistic model and a semi-empirical model based on the Weibull distribution. The two mathematical models provided the same rank order of the performance of the three drug products in terms of dissolution rates, but the rates were significantly different. The faster rate extracted from the mechanistic model is expected to reflect the true dissolution rate of the drug; the Weibull model provides an effective and slower rate that represents not only drug dissolution but also diffusion across the Transwell membrane. In conclusion, the developed extended model provides superior understanding of the dissolution mechanisms in membrane-type (Transwell) dissolution tests.

Most pulmonary drugs are immediate-release formulations with short duration of action. Controlled release systems provide the ability to deliver drugs at a controlled rate, which helps maintain drug concentrations within the therapeutic window for a longer period of time. This study aimed to produce microparticles (MPs) of hyaluronic acid hydrogel (HAGA) loaded with salbutamol sulphate (SS) for controlled release in the lung. The drugloaded MPs were prepared via spray drying and underwent extensive characterization, which revealed that SS was successfully encapsulated in the HAGA matrix. The prepared MPs (denoted as HASS) ranged in size from 1.6 & PLUSMN; 0.4 & mu;m to 1.7 & PLUSMN; 0.5 & mu;m with a fine particle fraction (FPF) of 48-56% and showed improvement in aerodynamic properties compared to unloaded HAGA hydrogel MPs. In vitro drug release studies performed in a Transwell system confirmed the potential of the particles to release the drug in a sustained manner. The drug release was delayed for all formulations, with a t63 between 5 and 30 min, compared to < 1min for pure SS. This study advances our understanding of the formulation of a highly soluble drug to achieve controlled release in the lung.