Novel Structured Particulates from a Scalable Mixed-Mode Crystallisation Platform
Lead Research Organisation:
University of Strathclyde
Department Name: Inst of Pharmacy and Biomedical Sci
Abstract
This project will investigate the potential of coupling multiple crystallisation methods for the generation active pharmaceutical ingredient (API) microstructure particles. Objectives for this process include: full process understanding of a baseline normal crystallisation for reference, selection of which crystallisation methods to couple (cooling, anti-solvent, evaporative, supercritical fluid, etc.), generate particle with a range of microstructures and testing of said microstructures for manufacturability and patient performance. This research will investigate how feasible it is to generate microstructured APIs, what range of structure properties are able to be generated and do these have any benefit with regards to either the manufacturing process or drug delivery to patient? Potential applications exist in the area of personalised medicines were the API particle could be tuned to a specific patient needs.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/R513349/1 | 01/10/2018 | 30/09/2023 | |||
| 2145630 | Studentship | EP/R513349/1 | 01/10/2018 | 30/09/2022 | Jenna Johnston |
| Description | Mechanistic modelling The focus of this work has been to build a model of the crystallisation of lactose from water under an array of conditions. In order to build this model, the kinetics of the process have been investigated experimentally in small batch processes. The crystallisation process is made up of a number of separate mechanisms that are competing within the system for solute molecules. This work originally looked to focus on the following mechanisms: volume diffusion, surface integration, agglomeration, primary and secondary nucleation. Since investigating the process under the chosen conditions the presence of nuceleation was found to be minimal except at the most extreme conditions being considered. Therefore, the inclusion of nucleation within the mechanistic model has not been considered at this time. Volume diffusion and surface integration are considered in terms of a two-step growth model and have been studied under a wide range of temperatures and concentrations. The growth mechanism has been developed into a growth-only mechanistic model at this stage with hopes to incorporate other mechanisms of crystallisation for the future of this work. Supercritical Fluid crystallisation A Supercritical Anti-Solvent (SAS) system was studied for the possible use as a method of crystallising lactose from Dimethyl sulfoxide (DMSO) under supercritical conditions. Initials investigations of the system with these compounds was found to produce very low yield. The set-up was then studied using paracetamol:ethanol solutions as this system has been investigated extensively in literature. The resulting yield was still very low and as such the limiting factor was highlighted as the mixing within the system rather than the system itself. A crude coaxial nozzle was then introduced to mix the supercritical fluid (SCF) and solution streams more efficiently. As such, the system is now more suitable for investigating crystallisation with supercritical fluids. Vacuum induced Evaporation crystallisation This work has focused on developing and studying an evaporative crystallisation set-up. The lactose:water solution being studied contains two forms of lactose in solution. The form of interest is alpha and can be crystallised out from water below 90 °C, above this temperature the crystallisation of the beta from will occur. This work looks to utilise vacuum as a method of inducing evaporation at lower temperatures in order to push the system to crystallise compounds usually unattainable via evaporative crystallisation at standard conditions. Currently the platform for these experiments has been developed and proven to produce lactose crystals via evaporation of water below 85 °C. The future for this work looks to focus on mechanistic modelling of the evaporation of water and the crystallisation process under these conditions. |
| Exploitation Route | The mechanistic model of the lactose crystallisation process can be used to predict the outcomes of chosen conditions in the replacement of copious experiments. The model can also be used as the basis for optimisation of preferable outcomes from the process based on the studied range of conditions. This type of interpolation is made possible by the models ability to simulate more conditions than have been directly studied. As such, there is a greater understanding of the crystallisation of lactose from water than would be gained from purely experimental research. The vacuum set-up that has been developed is also an interesting approach to recovery of specific crystals from a mixture of solutes in solution. The presence of different forms of sugars in aqueous solution is very common and this work could be utilised beyond the study of lactose. |
| Sectors | Pharmaceuticals and Medical Biotechnology |