Methods and Technologies:
Additive manufacturing (AM) enables the utilization of biodegradable polymers with different thermomechanical properties in pharmaceutical development. The use of biodegradable polymers in AM can be exploited to overcome challenges in drug formulation, such as low solubility and poor absorption. AM facilitates the production of amorphous solid dispersions (ASDs) with a flexible design that can achieve the desired drug release profile, making it a convenient method for enhancing the bioavailability of drugs with low solubility. ASDs typically involve mixing the drug with a polymer to form non-crystalline materials that can enhance drug solubility. Fused deposition modeling (FDM) is a common AM approach that uses a thermoplastic polymer that is melted and extruded layer-by-layer to create a desired shape. In the pharmaceutical industry, traditional manufacturing processes can lead to quality inconsistencies between batches, such as assay, drug release, and stability. On the other hand, AM is more economical, sustainable, and reproducible. It is a timesaving and solvent-free process that is easy to scale up.
In our project, we propose to use a model drug that has low solubility and/or low permeability.
Initially, we will use a variety of analytical tools to select suitable excipients for the model drug, study its solid-state changes, and develop a validated assay method for measurements.
In the second phase, we will develop a formulation of drug that can be compatible with FDM. Custom drug-loaded filaments will be created using an extruder, and we will fine-tune the drug loading. These extruded filaments will undergo mechanical and physicochemical testing and could incorporate one or more thermoplastic biodegradable polymers. In the development of custom drug-loaded filaments, measures will be taken to ensure that they possess suitable mechanical strength to resist handling without being damaged. Furthermore, custom drug-loaded filaments will be subjected to physicochemical testing to evaluate the effect of the degree of drug loading on mechanical properties and content uniformity.
In the third phase, we will optimize the critical process parameters, such as layer thickness, infill density, and temperature, to yield drug formulation with consistent quality and desired drug release profile.
Finally, we may optionally study the biorelevant permeability of the formulation by parallel artificial membrane permeability assays or by cell lines, namely the Caco-2 cell culture model. In vitro pharmacokinetic modelling or in vivo pharmacokinetic study on animal models will be conducted.
