The Effect of Milling on the Triboelectrification of Pharmaceutical Powders - Essay Example

The Effect of Milling on the Triboelectrification of Pharmaceutical Powders Abstract Pharmaceutical manufacturing processes involve making granular solids and eventually assembling them therapeutically into their respective dosage forms (Matsusaka et al. 2010). Designing the manufacturing process for capsules and tablets in pharmaceutical manufacturing involves identifying the quality factors of the product, formulating the product, designing the manufacturing process and finally evaluating the processes and the product to make sure that the product meets the quality standards. In manufacturing, two areas involve the making of the required granular material while the third involves processing and assembling a dosage. Milling is a process in manufacturing that involves particle size reduction. The resultant powder particles could charge themselves or be charged by the surfaces of the vessels. This paper examines the process of milling and the resultant triboelectrification effect and how to curb this phenomenon. Information would be collected from secondary sources including relevant journals and books. Introduction According to Crowder et al. (2003), pharmaceutical particulates could be produced either through constructive or destructive methods. Constructive methods include freeze-drying, supercritical fluid techniques and crystallisation. Of these three, the latter has been widely applied where the solid crystals would be produced by cooling, precipitating, evaporating or adding a solute or solvent to a liquid solution. This would cause nucleation which would result into crystal growth. Also known as lyophilisation, freeze-drying involves freezing, sublimation then finally secondary drying. Using supercritical fluids, re-crystallisation would occur through precipitation. Carbon dioxide has been commonly used as a supercritical fluid due its low critical temperature of 310C and also because it is inexpensive, non-toxic and non-flammable. Milling refers to the process of mechanically reducing the size of active pharmaceutical ingredients, APIs that are highly potent. In pharmaceutical milling, particles greater than 20 mesh would be produced through coarse milling, 200 to 20 mesh particles would be produced by intermediate milling and particles less than 200 mesh produced through fine milling. The aim of this would be to reduce the sizes and increase the surface area of these ingredients (Pingali, Tomassone & Muzzio 2010). Milling could be accomplished through communion, impaction, compression, shearing, attrition, cutting or grinding. The particles would therefore be subjected to a combination or one of compression, shear or tension forces. While compression crushes, shear and tension forces cut and elongate or pull apart respectively. The purpose of milling would be for these forces to increase the initial flaws that always exist on the particles. Above the yield value, the particles experience permanent deformation, hence the milling process. The rate of reduction depends on the initial size of the material, the reduction machine used, the material orientation in the machine and the period of subjection. The properties of the particles to be milled such as stickiness, moisture content, soapiness and hardness should be considered before embarking on the milling process. The choice of milling equipment would depend on the material type, its initial size, the material’s moisture content, the final size of the product needed and range of abrasion (Crowder et al. 2003). Coarse crushers do not have any use in pharmacy. Hammer and cutting mills constitute intermediate crushers while ball, fluid energy and oscillating granulator mills make up the fine crushers (Anderson 2012). Colloidal mills are also a classification of milling equipment. The advantages of this process includes increased rate of dissolution hence enhanced bioavailability. More so, milling improves important aspects in pharmaceutical manufacturing processes such as extraction rate, drying rate and flow rate. It improves mixing of ingredients so as to reduce discrepancies in content and weight uniformity of tablets. This ensures that dispersion of active ingredients and colour in tablet excipient diluents is uniform. Finally, this process controls the distribution of particle size in dry granulation so as to limit segregation during handling and tableting. Nonetheless, Kwok, Glover and Chan (2005) observe possible disadvantages of milling which include possibility of change in the API’s polymorphic form which limits its stability. Heat build-up during milling observed by Pu, Mazumder and Cooney (2009) could degrade the drugs through adsorption or oxidation as a result of increased surface area. Flow rate could also be limited due to decreased bulk density. Of importance to this paper would be the disadvantage of creation of static charge due to reduction in particle size which could lead to agglomeration of small drug particles which effectively reduces the surface area. This could further limit dissolution. Effect of milling on tribolelectrification Milling in pharmaceutical secondary manufacturing generates amorphous regions on the surfaces of the particles that exhibit thermodynamic instability that causes re-crystallisation upon storage (Pu, Mazumder & Cooney 2009). Without the presence of any electric fields, charging would occur either through friction or contact between two solid surfaces. While contact charging would encompass direct contact followed by subsequent separation of surfaces without any rubbing, frictional charging would call for relative movement of the contacting surfaces. Nonetheless, Kwok, Glover and Chan (2005) appreciate that in a physical interaction, these modes of charging would rarely be discerned independently. Therefore, the terminology tribolelectrification, with ‘tribo’ literally meaning rubbing has been used in describing the overall process. During milling, the contact between the particles that rub against one another and against the walls of the vessel leads to triboelectrification of the materials being milled. Anderson (2012) defines tribolelectrification as the ability of pharmaceutical powder to pick up charges when in contact with other materials which causes poor mixture of particles, especially the small ones. Triboelectrification occurs commonly in most industries handling powders such as detergents, foods and pharmaceuticals and depends on constitution of the powder, the surfaces of the manufacturing vessels, relative humidity and particle size. Manufacturing processes such as milling cause frequent contact among the particles and with the walls of the vessels. These interactions lead to charge transfer through friction, impact and shearing, a process referred to as triboelectric charging or triboelectrification (Supuk et al. 2011). Charging of particles leads to their change of behaviour causing them to easily adhere to each other or cause repulsion of other charged materials. When tribolelectrification occurs in excess, it could lead to adhesion, dust explosions, blockage or coating of pipelines or even loss of powder and difficulties in the control of powder flow (Matsusaka 2010; Pingali, Tomassone & Mizzio 2010). In the pharmaceutical industry, “pharmaceutical powders are usually semiconductors or insulators of small particle size and low bulk density, providing ideal conditions for electrostatic effects” (Supuk et al. 2011, p.209). Therefore, tribolelectrification could lead to segregation which compromises the quality of the end product. This would be manifested through susceptibility to change in the formulation of drugs in different processes like tabletting. The pharmaceutical industry operates under tight regulations that tightly monitor uniformity in content, thus the need for controlling electrostatic effect and ensuring that the end product meets safety and effectiveness standards. According to Anderson (2012), there would be a huge cost to pay in case of failure to control the physical form of APIs hindering adherence to the required standards which would result into the interruption of clinical trials or a ban on sale of such drugs. Supuk, Seiler and Ghadiri (2009) argue that understanding the magnitude of charge would be useful in developing pharmaceutical formulations which involve mixing of APIs and excipients so as to avoid loss of particles through wall adhesion. The accumulated charges in a silo during the loading of powder could cause high electric potentials on the surface of the heap which could cause electrostatic discharges. With higher discharge energies exceeding the powder’s minimum ignition energy, the heap could self-ignite. This would be particularly risky with dust clouds or flammable vapours in the vicinity. While attractive forces cause agglomeration of particles hence inhibited flow, repulsive forces reduce the density of the bulk powder and the powder blends’ physical stability. This affects formulation doses metering and filling of containers during manufacturing (Pu, Mazumder & Cooney 2009). Solution To minimise the effect of tribolelectrification, Supuk et al. (2011) proposes particle charging with opposite polarity so as to form stable ordered mixtures which minimise segregation. Studies by Matsusaka et al. (2010) indicate that co-milling stable amorphous with appropriate additives effectively minimised surface electrostatic charging. But cases have been recorded where both components have charged with same polarities hence propagating the adherence of particles to the inner walls of the vessels as opposed to adherence among the particles themselves. This could probably explain the popularity of cyclone charger as a tribocharging device that has interchangeable polymers and steel contact surfaces. Particles would be introduced through the sides using a carrier gas and would be charged through collision with the inside surfaces of the case cyclone charger. Nonetheless, this still suffers from the openness of its system with the risk of being exposed to active pharmaceutical ingredients, APIs. Conclusion In the process of therapeutically assembling granular solids into tablets, pharmaceutical industries undertake various manufacturing processes. Among these would be milling which has been considered as a size reduction process that involves application of various forces on particles to produce the required pharmaceutical particulates using various mills. During milling, the powder particles could be charged either through collision or by friction. This could be either through the particles charging themselves or through these particles rubbing against the inside walls of the manufacturing vessel. Referred to as triboelectrification, this causes the particles to either attract or repel other materials which eventually leads to possible outcomes such as difficulties in controlling powder flow, adhesion, blockages of pipelines and loss of powder. Various adaptations have been employed to reduce the effect of triboelectrification in pharmaceutical industries including co-milling and use of cyclone chargers, but the success rate still remains low. Reference Anderson, NG 2012, Practical process research and development – A guide for organic chemists, 2nd ed., Academic Press, Oxford, UK. Crowder, TM, Hickey, AJ, Louey, MD & Orr, N 2003, Pharmaceutical particulate science, Interpharm/CRC Press LLC, Boca Raton, Florida. Hickey, AJ, Mansour, HM, Telko, MJ, Xu, Z, Smyth, HDC, Mulder, T, McLean, R, Langridge, J & Papadopoulos, D 2007, ‘Physical characterisation of component particles in dry powder inhalers. II dynamic characteristics’, Journal of Pharmaceutical Sciences, vol. 96, no. 5, 1302 – 1319. Kwok, PCL, Glover, W & Chan, HK 2005, ‘Electrostatic charge characteristics of aerosols produced from metered dose inhalers’, Journal of Pharmaceutical Sciences, vol. 94, 2789–2799. Matsusaka, S, Marumaya, H, Matsumaya, T & Ghadiri, M 2010, Triboelectric charging of powders: A review, Journal of Chemical Engineering Science, vol. 65, 5781 – 5807. Pingali, KC, Tomassone, MS & Muzzio, F 2010, Effects of shear and electrical properties on flow characteristics of pharmaceutical blends, Journal of American Institute of Chemical Engineers, vol. 56, no. 3, 570 – 582. Pu, Y, Mazumder, M & Cooney, C 2009, Effects of electrostatic charging on pharmaceutical powder blending homogeneity, Journal of Pharmaceutical Sciences, vol. 98, no. 7 Supuk, E, Hassanpour, A, Ahmadian, H, Ghadiri, M & Matsuyama, T 2011, ‘Tribo-electrification and associated segregation of pharmaceutical bulk powders’, KONA Powder and Particle Journal, vol. 29, pp. 208 – 221. Supuk, E, Seiler, C & Ghadiri, M 2009, Analysis of a sample test device for tribo-electric charging of bulk powders, Particulate Particles System Character Journal, vol. 26, 7 – 16. Read More