Many of the ingredients used in the formulation of pharmaceutical oral solid dosage (OSD) forms have been shown to be combustible. Generally, the fire and explosion hazards associated with flammable solvents are well understood. However, hazards associated with solid ingredients are less so.
When assessing dust cloud flash fire and explosion hazards one should not only consider the active pharmaceutical ingredients (API) but also the excipient ingredients that are used. In order to evaluate the potential explosion hazards associated with the use of powders/dusts, the following data (also shown in Table 1) are usually relevant:
- Explosion Screening/Classification (is the dust cloud explosible?): Determining whether the dust cloud will explode (create pressure or flame that propagates away from the ignition source) when exposed to an ignition source.
- Minimum Explosible Concentration (MEC): The lowest concentration of dust suspended in air that can give rise to flame propagation upon ignition.
- Minimum Ignition Temperature, Dust Cloud (MIT-Cloud): The lowest temperature capable of igniting the dust dispersed in the form of a cloud.
- Minimum Ignition Temperature, Dust Layer (MIT-Layer): The lowest surface temperature capable of igniting a dust layer of standard thickness (5 to 12.7 mm depending on test method)
- Self-Heating: Ignition of bulk powders can occur by a process of self-heating when the powder temperature is raised to a level at which the heat liberated by the exothermic oxidation or decomposition reaction is sufficient to exceed the heat losses and produce a “runaway” increase in temperature.
- Minimum Ignition Energy (MIE): The lowest electrical spark energy that is capable of igniting the dust cloud at its optimum concentration for ignition. MIE data is used primarily to assess the susceptibility of dust clouds to electrostatic discharges/sparks.
- Electrostatic Chargeability: The propensity of powder particles to become charged when flowing through conveyances or during handling and processing
- Volume Resistivity: The primary criterion for classifying powders as low, moderately, or highly insulating. Insulating powders have a propensity to retain electrostatic charge and can produce hazardous electrostatic discharges when exposed to grounded facilities, equipment, or personnel.
- Limiting Oxidant Concentration (LOC): The minimum concentration of oxygen (displaced by an inert gas such as nitrogen or carbon dioxide) capable of supporting combustion. An atmosphere having an oxygen concentration below the LOC is not capable of supporting a dust explosion.
- Explosion Severity (Maximum Explosion Pressure and Maximum Rate of Pressure Rise): The maximum rate of pressure rise is measured and used to calculate the deflagration index (Kst) value of the dust cloud. These data are used to design dust explosion protection measures.
- Explosibility Screening test is only conducted if the combustibility of the powder/dust (present in the process/facility) is not yet established. If the dust is found to be non-combustible, other tests in the table may not be required.
- MIT-cloud and MIT-layer may be required for equipment temperature rating specification in Class II classified areas of buildings/rooms.
- LOC is determined if the basis of safety is inert gas blanketing.
- Volume Resistivity should be considered if the Minimum Ignition Energy is less than 25mJ.
- Chargeability should be considered if the Minimum Ignition Energy is less than 25mJ.
Table 2 lists the properties of a number of common pharmaceutical excipients from a number of publically available sources. It should be noted that these properties are dependent upon parameters such as: particle size, moisture content, oxidant concentration, and the presence of flammable vapors; and caution should be exercised in their use.
Table 2. Examples of Properties of Pharmaceutical Excipients
As stated earlier, when handling combustible solid materials, an explosion hazard is present whenever the fine particulate becomes suspended in air. This may be intentional (fluidized bed drying) or unintentional, such as during vessel charging. Operations where dust explosion hazards must be considered during the design and operation of an OSD facility will typically include: powder charging operations, blending, granulation, drying, milling, compression/coating, and dust collection. A primary Basis of Safety needs to be defined and documented for each operation. Common options are summarized in Table 3.
Table 3. Typical Bases of Safety for Some Pharmaceutical Unit Operations
1. NFPA 68, “Venting of Deflagrations”
2. NFPA 69, “Standard on Explosion Prevention Systems”
Dr. Vahid Ebadat Ph.D., M.Inst.P, MIEE, C.Eng., C.Phys. is the CEO of Chilworth North America. He has worked extensively as a process and operational hazards consultant for the chemical, pharmaceutical and food industries and can be reached at firstname.lastname@example.org.