Many of the solid ingredients, or excipients, used in the formulation of pharmaceutical oral solid dosage (OSD) forms have been shown to be combustible. As a result, operations typically found in this type of facility have the potential to generate explosible dust cloud atmospheres. Recognized explosion, or deflagration hazards will necessarily influence process equipment specifications, design of air handling and conditioning systems, electrical area classification, and room construction in order to achieve applicable code compliance. It is therefore necessary for OSD manufacturers to clearly understand the explosion hazards presented by the materials utilized in their processes, and be able to assess the level of explosion risk that their operations may present. This article presents guidance for safe handling of combustible solids in Pharmaceutical OSD facilities, by applying a Basis of Safety.
Explosion hazards associated with the use of flammable solvents such as acetone, isopropyl alcohol (IPA), methanol, and others used in tablet coating and equipment cleaning operations, are well understood and controlled. The explosion hazards associated with solid pharmaceutical ingredients tend to be less well understood or controlled.
An explosion hazard may exist when a sufficient quantity of finely divided solid particles becomes suspended in an atmosphere containing an oxidant. In pharmaceutical facilities the oxidant is typically atmospheric air present within the processing equipment. Although some manufacturers are well aware of the explosion hazards associated with their active pharmaceutical ingredients (API), however the explosion hazards of the excipients are often overlooked.
Most compounds that are not already stable oxides can potentially give rise to solid in air explosions including: natural organic materials, synthetic organic materials, and metallics. Table 1 lists published data for some materials commonly used as excipients in the pharmaceutical industry that have been experimentally shown to present an explosion hazard.
In order to evaluate the explosion hazards associated with the use of these solid materials, it is necessary to have accurate explosibility data. The requirements will vary depending upon the process operations, with relevant data typically including the Explosion Severity (Kst), Minimum Ignition Energy (MIE), Minimum Ignition Temperature (MIT), Minimum Explosible Concentration (MEC), and Limiting Oxygen Concentration (LOC). If the material is determined to be sensitive to ignition from electrostatic discharges (i.e. having an MIE of less than 25 mJ), electrostatic properties such as the Volume Resistivity and Chargeability (mass charge density) of the powder may also be relevant.
Dust Explosion Hazards in Specific OSD Operations
An explosion hazard is present when handling combustible solid materials whether particle suspension is by design, (fluidized bed drying) or unintentional, such as during vessel charging. Operations where dust explosion hazards must be considered during the design of an OSD facility include: material charging operations, blending, granulation, drying, milling, compression, coating, and dust collection.
During the design phase of a new or proposed process or subsequent review of an existing process, a primary Basis of Safety needs to be defined and documented for each operation. The selected basis of safe operation will be a function of: the type of operation, potential ignition sources, and the explosibility properties of the materials being handled. The basis of safety will focus on achieving explosion prevention or mitigation. Technologies that have been successfully used in the pharmaceutical industry are shown in Table 2.
When selecting a basis of safety, consideration should be given to the effectiveness of each method, reliability of the safety systems, and the potential personnel hazards inherent in each method. Further guidance on the applicability and design of such systems can be found in NFPA 68 “Venting of Deflagrations” and NFPA 69 “Explosion Prevention Systems”, and NFPA 654 “Standard For The Prevention of Fire and Dust Explosions from the Manufacturing, Processing, and Handling of Combustible Particulate Solids”.
Other Facility Design Considerations
The safe processing of combustible solid materials may also require modifications to the design of the facility itself. In areas of the facility where dust explosion hazards can exist external to processing equipment, building codes may require the process room to be provided with explosion venting or blast resistant walls. These added features may be costly and difficult to achieve. Recognizing the potential for dust explosion hazards early in the life cycle of a project or process may avoid this situation of challenging retrofit.
Incorrectly specified electrical equipment may provide a ready source of ignition for combustible dust in air mixtures. In areas where combustible materials are to be handled, an electrical area classification should be conducted. The National Fire Protection Association outlines the requirements for electrical systems in areas where combustible dust may be present. (NFPA 499 and NFPA 70). Elimination of potential ignition sources, though not as reliable as the control of oxidant, should be attempted to contribute to the Basis of Safety.
A Summary of Key Factors for Explosion Hazard Control
Effective control of the explosion hazard associated with the manufacture of pharmaceutical OSD forms begins with application of the following points:
• Evaluate the materials being processed.
• Identify areas where combustible atmospheres of solid materials may be formed.
• Identify potential ignition sources.
• Define a Basis of Safety for the operation early in the project or process life cycle.
• Effectively communicate the potential hazard and control strategy to operations personnel and third parties such as architects, engineers, equipment suppliers and consultants.
• Document the basis of safe operation for future training and review.
1. Eckhoff R.K., “Dust Explosions in the Process Industries”, Butterworth-Heinemann, 1991.
2. Field, P., “Handbook of Powder Technology”, Elsevier, 1982.
3. NFPA 68, “Venting of Deflagrations”, 1998.
4. NFPA 69, “Standard on Explosion Prevention Systems”
5. NFPA 70, “National Electrical Code®”
6. NFPA 499, “Recommended Practice for the Classification of Combustible Dusts and of Hazardous (Classified) Locations for Electrical Installations in Chemical Process Areas”
7. NFPA 654, “Standard For The Prevention of Fire and Dust Explosions from the Manufacturing, Processing, and Handling of Combustible Particulate Solids”
About the author: 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. For additional information regarding this article, please contact Dr. Vahid Ebadat at 609-799-4449 or email firstname.lastname@example.org or visit: www.chilworth.com.