# Powder mixture

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{{Short description|Mixture of dry particles}}
A powder is an assembly of dry particles dispersed in air. If two different powders are mixed perfectly, theoretically, three types of '''powder mixtures''' can be obtained: the random mixture, the ordered mixture or the interactive mixture.

== Different powder types ==
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A [powder](/source/Powder_(substance)) is called '''free-flowing''' if the particles do not stick together. If particles are [cohesive](/source/cohesion_(chemistry)), they cling to one another to form [aggregate](/source/Particle_aggregation)s. The significance of cohesion increases with decreasing size of the powder particles; particles smaller than 100 [μm](/source/micrometre) are generally cohesive.<ref>{{cite journal|author=J. Bridgewater|doi=10.1016/0032-5910(76)80051-4|title= Fundamental powder mixing mechanisms|journal=Powder Technol. |pages=215–236|year=1976|volume=15|issue=2}}</ref><ref>{{cite journal|author1=N.A. Orr  |author2=E. Shotton |name-list-style=amp |title= The mixing of cohesive powders|journal=The Chemical Engineer|volume= 269|pages=12–18|year=1973}}</ref>

File:Powder mixtures.jpg

== Random mixture ==
A '''random mixture''' can be obtained if two different free-flowing powders of approximately the same particle size, [density](/source/density) and [shape](/source/shape) are mixed (see figure A).<ref name="avhandlingar.se">{{Cite web|url=https://www.avhandlingar.se/avhandling/479d31e775/|title = AVHANDLINGAR.SE: Studies on a Novel Powder Formulation for Nasal Drug Delivery}}</ref> Only primary particles are present in this type of mixture, i.e., the particles are not cohesive and do not cling to one another. The mixing time will determine the quality of the random mixture. However, if powders with particles of different size, density or shape are mixed, [segregation](/source/Particle_segregation) can occur.<ref>{{Cite journal|last1=Alizadeh|first1=Mohammadreza|last2=Hassanpour|first2=Ali|last3=Pasha|first3=Mehrdad|last4=Ghadiri|first4=Mojtaba|last5=Bayly|first5=Andrew|date=2017-09-01|title=The effect of particle shape on predicted segregation in binary powder mixtures|journal=Powder Technology|volume=319|pages=313–322|doi=10.1016/j.powtec.2017.06.059|issn=0032-5910|url=http://eprints.whiterose.ac.uk/118401/3/Manuscript-Mohammadreza%20Alizadeh%20et%20al.pdf}}</ref> Segregation will cause separation of the powders as, for example, lighter particles will be prone to travel to the top of the mixture whereas heavier particles are kept at the bottom.

== Ordered mixture ==
The term ''ordered mixture'' was first introduced to describe a completely [homogeneous](/source/Homogeneous_(chemistry)) mixture where the two components adhere to each other to form ordered units.<ref>{{cite journal|author=J.A. Hersey|title= Ordered mixing: a new concept in powder mixing practice|journal=Powder Technol|volume= 11|pages=41–44|year=1975|doi=10.1016/0032-5910(75)80021-0}}</ref> However, a completely homogeneous mixture is only achievable in theory and other denotations were introduced later such as adhesive mixture or interactive mixture.

== Interactive mixture ==
If a free-flowing powder is mixed with a cohesive powder an '''interactive mixture''' can be obtained. The cohesive particles adhere to the free-flowing particles (now called carrier particles) to form interactive units as shown in figure B.<ref name="avhandlingar.se"/> An interactive mixture may not contain free aggregates of the cohesive powder, which means that all small particles must be adhered to the larger ones. The difference from an ordered mixture is instead that all carrier particles do not need to be of the same size and a different number of small particles attached to each one. A narrow size range of the carrier particles is preferred to avoid segregation of the interactive units.<ref>{{cite journal|author1=C.W. Yip  |author2=J.A. Hersey |name-list-style=amp |title=Segregation in ordered powder mixtures|journal=Powder Technol|volume= 16|pages=149–150|year=1977|doi=10.1016/0032-5910(77)85034-1}}</ref> In practice a combination of a random mixture and an interactive mixture may be obtained which consists of carrier particles, aggregates of the small particles and interactive units.<ref>{{cite journal|author=J.N. Staniforth|title= Total mixing|journal= Int J Pharm Tech & Prod MFR|volume= 2|pages=7–12|year=1981}}</ref>

===Formation===
The formation of interactive mixtures cannot automatically be assumed, especially if smaller carrier particles <ref>{{cite journal|author1=C.C. Yeung  |author2=J.A. Hersey |name-list-style=amp |title= Ordered powder mixing of coarse and fine pariculate systems|journal=Powder Technol|volume= 22|pages=127–131|year=1979|doi=10.1016/0032-5910(79)85015-9}}</ref> or a greater proportion of fine particles <ref>{{cite journal|author1=P. Kulvanich  |author2=P.J. Stewart |name-list-style=amp |title= The effect of particle size and concentration on the adhesive characteristics of a model drug-carrier interactive system|journal= J Pharm Pharmacol|volume= 39|pages=673–678|year=1987|pmid=2890731|issue=9|doi=10.1111/j.2042-7158.1987.tb06968.x|s2cid=6880102 }}</ref><ref>{{cite journal|author1=A.H. de Boer |author2=P.P. Le Brun |author3=H.G. van der Woude |author4=P. Hagedoorn |author5=H.G. Heijerman |author6=H.W. Frijlink  |name-list-style=amp |title= Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle|journal= Eur J Pharm Biopharm|volume=54|pages=17–24|year=2002|doi=10.1016/S0939-6411(02)00043-7|pmid=12084498|issue=1}}</ref> are used. If an interactive mixture is to be formed, it is necessary that enough force is exerted by the carrier particles during dry mixing to break up the aggregates formed by the fine particles. Adhesion can then be achieved if the adhesive forces exceed the gravitational forces that otherwise lead to separation of the constituents.<ref name="avhandlingar.se"/>

===Applications===
Interactive mixtures for example can be used in the manufacturing of tablets<ref>Bredenberg, Susanne  [http://uu.diva-portal.org/smash/record.jsf?pid=diva2:162788 New Concepts in Administration of Drugs in Tablet Form : Formulation and Evaluation of a Sublingual Tablet for Rapid Absorption, and Presentation of an Individualised Dose Administration System]. Doctoral thesis (2003). Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy</ref> enhancing the dissolution of poorly [soluble](/source/soluble) [drug](/source/drug)s <ref>{{cite journal|author1=C. Nystrom  |author2=M. Westerberg |name-list-style=amp |title= The use of ordered mixtures for improving the dissolution rate of low solubility compounds|journal= J Pharm Pharmacol|volume= 38|pages=161–165|year=1986|pmid=2871148|issue=3|doi=10.1111/j.2042-7158.1986.tb04537.x|s2cid=23665573 }}</ref> or for [nasal administration](/source/nasal_administration).<ref name="avhandlingar.se"/> One common application is for inhalation therapy, where the concept has been used in the development of alternatives to pressurised metered dose inhalers.<ref>{{cite journal|author=H. Steckel and B. Müller. In vitro evaluation of dry powder inhalers I: drug deposition of commonly used devices|journal= Int J Pharm|volume=154|pages=19–29|year=1997|doi=10.1016/S0378-5173(97)00113-0|title=In vitro evaluation of dry powder inhalers I: Drug deposition of commonly used devices}}</ref>

The [quality by design](/source/Quality_by_Design) initiative (QbD) of the [U.S. Food and Drug Administration](/source/Food_and_Drug_Administration) requires a process to be controllable and predictable. Theories and methods to characterize powder mixture have facilitated the implementation of QbD approaches to predict flow properties of powder mixture. For example, QbD approach is shown to be useful for predicting flow performance and finding design space during formulation development.<ref>{{Cite journal|last1=Wang|first1=Yifan|last2=Snee|first2=Ronald D.|last3=Meng|first3=Wei|last4=Muzzio|first4=Fernando J.|date=2016-06-01|title=Predicting flow behavior of pharmaceutical blends using shear cell methodology: A quality by design approach|journal=Powder Technology|volume=294|pages=22–29|doi=10.1016/j.powtec.2016.01.019|issn=0032-5910}}</ref>

== References ==
{{Reflist|35em}}

==External links==
*[http://rxtimes.com/improving-powder-flow-during-pharmaceutical-operations/ Improving Powder Flow During Pharmaceutical Operations], an Rx Times article
Category:Granularity of materials
Category:Food technology
Category:Materials science
Category:Routes of administration
Mixture

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Adapted from the Wikipedia article [Powder mixture](https://en.wikipedia.org/wiki/Powder_mixture) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Powder_mixture?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.