Influence of Liquid and Vapourized Solvents On Explosibility of Pharmaceutical Excipient Dusts

Hybrid mixture explosion research is typically conducted with three possible approaches: (i) gaseous solvent at room temperature existing in the combustion atmosphere prior to dust dispersal, (ii) liquid solvent at room temperature requiring flashing-off for admixture to the combustion atmosphere prior to dust dispersal, and (iii) liquid solvent at room temperature admixed as a liquid with the dust prior to dust dispersal.

The current project utilizes the latter two of the above approaches with common pharmaceutical excipients and solvents – lactose and microcrystalline cellulose (MCC), and methanol, ethanol and isopropanol, respectively. All materials tested are pharmaceutical-grade in terms of composition and, in the case of the solids, particle size distribution.

Explosibility parameters investigated include maximum explosion pressure (P_max), size-normalized maximum rate of pressure rise (K_St), minimum explosible concentration (MEC), minimum ignition energy (MIE), and minimum ignition temperature (MIT). ASTM protocols are being followed using standard dust explosibility test equipment (Siwek 20-L explosion chamber, MIKE 3 ignition energy apparatus, and BAM oven for ignition temperature measurement).

Because the MIKE 3 apparatus and BAM oven are not closed systems, only baseline excipient-alone testing and excipient pre-wetted with solvent testing are possible for MIE and MIT determination in our laboratory. With the Siwek 20-L  chamber (i.e., a closed system), however, it is feasible to conduct P_max, K_St and MEC testing for all three cases of the dust alone, pre-wetted with solvent, and with solvent admixed to the combustion atmosphere prior to dust dispersal.

At the time of writing, P_max, K_St, MEC, MIE and MIT tests have been conducted (with ongoing data analysis) for lactose and MCC, and also for each dust pre-wetted with methanol, ethanol and isopropanol at 80 % of the lower flammability limit for each solvent. Testing is currently underway for P_max, K_St and MEC of the dusts with solvent admixed directly to the combustion atmosphere.

As preliminary commentary, we offer the following thoughts on data trends. In all cases, pre-wetting of MCC and lactose with solvent had a measurable impact on each explosibility parameter (P_max, K_St, MEC, MIE and MIT). As expected, the influence was generally an enhancement of the particular parameter (e.g., increase in K_St, decrease in MIE, etc.); the lone exception was P_max for MCC which displayed a decrease of 0.6-0.8 bar(g) with solvent admixture. Additionally, while the magnitude of the effect of solvent admixture to MCC was generally distinguishable for the different solvents, this was not the case for lactose. Pre-wetting of lactose with each of the three solvents resulted in similar values of P_max, K_St and MIE.

It therefore appears that burning velocity considerations alone may adequately account for the enhanced K_St values brought about by solvent pre-wetting of microcrystalline cellulose (with laminar burning velocities of 56 cm/s for methanol, 42 cm/s for ethanol and 41 cm/s for isopropanol). As indicated above, this does not appear to be the case for solvent pre-wetting of lactose. Consideration of physical properties such as solvent latent heat of vaporization, and excipient heat capacity and solubility, may be required to attempt a phenomenological explanation of the observed data trends. It is anticipated that further insight will be provided by the ongoing experiments with solvent admixture by flashing-off into the partially evacuated 20-L chamber prior to dust dispersal.