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processes, it is critical to feed powders consistently and accurately into subsequent unit operations of the process line, as feeding is typically the first unit operation. Feeders have been designed to achieve performance reliability, feed rate accuracy, and minimal disturbances. Accurate and consistent delivery of materials by well-designed feeders ensures overall process stability. Loss-in-weight (LIW) feeders are selected for pharmaceutical manufacturing. Loss-in-weight (LIW) feeders control material dispensing by weight at a precise rate and are often selected to minimize the flowrate variability that is caused by change of fill level and material bulk density. Importantly, feeding performance is strongly dependent on powder flow properties.
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addressed to achieve target product quality attributes. These variables may include the particle size distribution (including aggregates or lumps of material), particle shape (spheres, rods, cubes, plates, and irregular), presence of moisture (or other volatile compounds), particle surface properties (roughness, cohesion), and powder flow properties.
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process involves the application of heat, pressure and agitation to mix materials together and 'extrude' them through a die. Twin-screw high shear extruders blend materials and simultaneously break up particles. The resulting particles can be blended and compressed into tablets or filled into capsules.
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In general, there are two types of granulation: wet granulation and dry granulation. Granulation can be thought of as the opposite of milling; it is the process by which small particles are bound together to form larger particles, called granules. Granulation is used for several reasons. Granulation
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In the pharmaceutical industry, a wide range of excipients may be blended together with the active pharmaceutical ingredient to create the final blend used to manufacture the solid dosage form. The range of materials that may be blended (excipients, API), presents a number of variables which must be
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Whether to add organic solvent into aqueous solvent, or vice versa, becomes important on the industrial scale. Depending on the solvents used, emulsions can form, and the time needed for the layers to separate can be extended if the mixing between solvents is not optimal. When adding organic solvent
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information about the production and control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, the site master file needs to describe
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Hot melt extrusion is utilized in pharmaceutical solid oral dose processing to enable delivery of drugs with poor solubility and bioavailability. Hot melt extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier increasing dissolution rates and bioavailability. The
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The documentation of activities by pharmaceutical manufacturers is a license-to-operate endeavor, supporting both the quality of the product produced and satisfaction of regulators who oversee manufacturing operations and determine whether a manufacturing process may continue or must be terminated
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In continuous manufacturing, input raw materials and energy are fed into the system at a constant rate, and at the same time, a constant extraction of output products is achieved. The process's performance is heavily dependent on the stability of the material flowrate. For powder-based continuous
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organic compounds in only mildly acidic or basic conditions. In an even wider scope, the location of the chemical plant can play a role in the ambient temperature of the reaction vessel. A difference of even a couple of degrees can yield much different levels of extractions between plants located
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of the reagents typically also increases as the temperature lowers, leading to difficult mixing. This results in added costs to stir harder and replace parts more often, or it results in a non-homogeneous reaction. Finally, lower temperatures can result in crusting of reagents, intermediates, and
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ratios of reagents can result in different ratios of products formed. On the industrial scale, adding a large amount of reagent A to reagent B may take time. During this, the reagent A that is added is exposed to a much higher stoichiometric amount of reagent B until it is all added, and this
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prevents the "demixing" of components in the mixture, by creating a granule which contains all of the components in their required proportions, improves flow characteristics of powders (because small particles do not flow well), and improves compaction properties for tablet formation.
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148:, milling is often required in order to reduce the average particle size in a drug powder. There are a number of reasons for this, including increasing homogeneity and dosage uniformity, increasing
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152:, and increasing the solubility of the drug compound. In some cases, repeated powder blending followed by milling is conducted to improve the manufacturability of the blends.
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as a cooling agent for reaction selectivity, this process gets complicated on an industrial scale. The cost to cool a typical reactor to this temperature is large, and the
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Blackshields, Caroline A.; Crean, Abina M. (3 July 2018). "Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review".
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imbalance can lead to reagent A prematurely reacting, and subsequent products to also react with the huge excess of reagent B.
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Cartwright, James J.; Robertson, John; D'Haene, Dorie; Burke, Matthew D.; Hennenkamp, Jeffrey R. (1 April 2013).
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398:"Twin screw wet granulation: Loss in weight feeding of a poorly flowing active pharmaceutical ingredient"
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405:. Special Issue: 5th International Granulation Workshop Granulation across the length scale 2011.
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195:. The document is created by a manufacturer. The Site Master file contains specific and factual
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byproducts to the reaction vessel over time, which will impact the purity of the product.
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Wang, Yifan; Li, Tianyi; Muzzio, Fernando J.; Glasser, Benjamin J. (15 February 2017).
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to aqueous, stoichiometry must be considered again, as the excess of water could
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547:"PIC/S explanatory notes for industry on the preparation of a site master file"
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44:. The process of drug manufacturing can be broken down into a series of
553:. Australian Government, Department of Health and Ageing. Archived from
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275:. Maharashtra, India: Blockdale Media. pp. 51–56. Archived from
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82:
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462:"Pharmaceutical Drug Formulation, Development & Drug Delivery"
356:"Predicting feeder performance based on material flow properties"
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which provides information about the production and control of
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Toledo
Pharmacal Company from Toledo, Ohio seen in 1905
495:. China: Churchill Livingstone Elsevier. p. 465.
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200:only those operations, e.g., analysis, packaging.
569:"WHO: Guidelines for drafting a Site Master File"
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491:Aulton, Michael; Malcolm, Summers, eds. (2013).
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578:. World Health Organization. Archived from
466:Particle Sciences Drug Development Services
122:Powder feeding in continuous manufacturing
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295:Pharmaceutical Development and Technology
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436:Baxter, Thomas; Prescott, James (2009).
187:A Site Master File is a document in the
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266:"How to Minimize Scale Up Difficulties"
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576:Prequalification of Medical Products
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32:is the process of industrial-scale
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438:Developing Solid Oral Dosage Forms
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16:Synthesis of pharmaceutical drugs
551:Therapeutic Goods Administration
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523:(Definition). Archived from
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373:10.1016/j.powtec.2016.12.010
30:Pharmaceutical manufacturing
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264:Laird, Trevor (July 2010).
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77:While a laboratory may use
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517:"Extrusion Spheronisation"
468:. Lubrizol. Archived from
225:Pharmaceutical formulation
146:drug manufacturing process
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273:Chemical Industry Digest
230:Pharmaceutical packaging
193:manufacturing operations
220:Medical science liaison
189:pharmaceutical industry
68:Scale-up considerations
42:pharmaceutical industry
183:Site Master File (SMF)
26:
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210:Chemical engineering
38:pharmaceutical drugs
585:on 24 January 2013.
103:Solvent extractions
603:Drug manufacturing
472:on 10 October 2015
440:. Academic Press.
165:Hot melt extrusion
113:across countries.
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527:on 1 October 2016
502:978-0-7020-4290-4
447:978-0-444-53242-8
403:Powder Technology
360:Powder Technology
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215:Chemical reactor
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62:tablet pressing
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409:: 116–121.
366:: 135–148.
156:Granulation
144:During the
54:granulation
476:24 October
316:10468/4633
297:(Review).
246:References
94:Different
48:, such as
521:PharmaCMC
423:0032-5910
382:0032-5910
341:205750263
325:1083-7450
110:hydrolyze
83:viscosity
34:synthesis
597:Category
333:28590824
204:See also
140:Milling
79:dry ice
73:Cooling
58:coating
50:milling
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583:(PDF)
572:(PDF)
337:S2CID
280:(PDF)
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533:2016
497:ISBN
478:2015
442:ISBN
419:ISSN
378:ISSN
329:PMID
321:ISSN
411:doi
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197:GMP
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
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