Determining measured experimental values of density to aid formulation development of new environmentally friendly propellant mixtures with Ethanol
Lauren Harrison1
1Kindeva Drug Delivery Limited, Derby Road, Loughborough, UK, LE11 5SF
Summary
Kindeva have been working on multiple projects with greener propellants, hydrofluoroolefin (HFO) 1234ze(E) and hydrofluoroalkane (HFA) 152a to assess their suitability to replace the current HFA 134a and HFA 227 as greener alternatives.
A key property of propellants to consider when formulating pressurised metered dosage inhalers (pMDIs) is density, due to its direct impact on characteristics of the formulation and calculations to determine exact quantities of each component required. When there are no additional excipients, the formulation density is the same as the liquid propellant density and this value is used when determining quantities of the formulation.
However, as additional excipients such as co-solvents are added to the formulation the overall density of the formulation will change. Historically, this has been well characterised for HFA 134a and HFA 227, but with the change to greener propellants, these density values need to be determined experimentally.
Kindeva therefore assessed the effect of increasing levels of Ethanol on density of HFA 152a and HFO 1234ze(E) containing formulations to improve accuracy when formulating by measuring actual experimental values. See Table 1 below that shows the change in overall formulation density for HFA 152a as Ethanol % increases.
Table 1: Measured Density Values of HFA 152a and HFO 1234ze(E) with increase of Ethanol
| 152a | 1234ze(E) | |
| Ethanol (% w/w) | Average Measured Density (g/mL) | |
| 0% | 0.9173 | 1.1786 |
| 20% | 0.8972 | 1.0764 |
| 40% | 0.8748 | 0.9870 |
| 50% | 0.8594 | 0.9453 |
The results of the study showed a clear correlation with reduction in density as the Ethanol level increased in each propellant and therefore highlighted the need to re-model a suitable calculation for the greener propellants, HFA 152a and HFO 1234ze(E).
Key Message
By measuring the formulation density with increasing levels of Ethanol in new propellants, it has been possible to highlight the need for a new model for HFA 152a and HFO 1234ze(E) for use in development programmes as a predictive tool for formulation activities in pMDI’s.