Mixing of Pharmaceutical Powders
Session 9: Mixing of Pharmaceutical Powders
Total Session Time: 120 minutes
Pre-requisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes|Presentation |Introduction, Learning Tasks |
|2 |15 minutes|Presentation |Definitions |
|3 |10 minutes|Brainstorming |Reasons for Mixing |
| | |Presentation | |
|4 |20 minutes|Presentation |Types of Powder Mixtures |
|5 |30 minutes|Presentation |Mechanisms of Mixing and De-mixing of |
| | | |Powders |
|6 |30 minutes|Presentation |Mixing Techniques and Equipments |
|7 |05 minutes|Presentation |Key Points |
|8 |05 minutes|Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing
STEP 2: Definition (15 minutes)
manufacture of pharmaceutical dosage forms constitute in the powder form
o Hence handling and processing of powders is central to pharmaceutical
operations
manufacturing
o Mixing is defined as a process of thoroughly combining different
materials to achieve a homogenous product
e.g. a drug and a diluents although at times, a chemically
homogenous material is mixed to uniformly distribute its large
range of particle sizes
o Mixing of powder is a shuffling type unit operation process involving
both large and small particle groups and even individual particles
o Mixing is an energy consuming process which produces a random
distribution of particles
o Optimum mixing is a prerequisite for manufacturing of solid dosage
forms which involve powder mixing and it has a critical contribution
in achieving uniformity of content
STEP 3: Reasons for Mixing (10 minutes)
|Activity: Brainstorming (5 minutes) |
| |
|ASK students to brainstorm on the following question: |
| |
|What are the reasons for mixing powders? |
| |
|ALLOW few students to respond? |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
o To ensure an even distribution of the active component(s)
o To ensure an even appearance of the dosage form
o To ensure that the dosage form releases the drug at the correct site
and at the desired rate
o To ensure colour uniformity since powders differs in colour
STEP 4: Types of Powder Mixtures (20 minutes)
o Free flowing powders have desirable features like minimal need of
lubricant and effective contact with die cavity
o They suffer from a serious drawback of segregation of individual
components in post mixing processing
o The particles can move smoothly and independently in a particular
direction due to the inter-particulate forces
o The free flowing powders need to be handled and stored in a proper
manner by packing the products in polythene bags and applying vacuum,
before sealing.
o The cohesive mixture exhibits “stick-slip” characteristics and the
components are not free flowing, the individual particles are
repeatedly broken down and allowed to redistribute within the system
to ensure a satisfactorily mixed product. The scale of segregation is
less, but the intensity of segregation will be more due to the
retaining of structure by the small agglomerates throughout the mixing
process
o Some of the parameters contributing to the formation of cohesive
mixtures are moisture, electrostatic charges, Van der waals forces and
solid bridges between the particles
o If one of the constituents of the powder mix is added to a fine,
micronized form then on mixing the larger particles may adsorb some of
these smaller particles to active sites on their surface where they
are held tenaciously
o Ordered mixtures are formed by mechanical, adhesion or coating forces
such that the ordered unit will be the smallest possible sample of the
mix and will be of near identical compositions to all other ordered
units in the mix
STEP 5: Mechanisms of Mixing and De-mixing of Powders (30 minutes)
o Diffusion blending is characterised by the random motion of solid
particles i.e. diffusive movement of individual particles
(Micromixing)
o It occurs where the particles are distributed over a freshly
developed interface
o It is a slow blending mechanism
o This type of mixing is achieved by tumbler mixers
o Mixing by convection is characterised by random motion of solid
particles whereby blending groups of particles (a large portion of the
powder bed) are rapidly moved from one position to another due to the
action of a rotating agitator (Macromixing)
o The movement of solid particles through the mixer is either by a force
action from a paddle or by gentle tumbling under rotational effects
o The blending of solids in ribbon blenders and paddle mixer is mainly a
result of convective mixing
o Shear mixing is achieved by the removal of force of attraction between
the powder particles
o Shear blending as the development of slip planes or shearing strains
within a bed of material
o Shear mixing reduces the scale of segregation
o Blenders with high speed chopper blades and intensifiers are examples
of shear blending equipments
o All powder mixture have variable tendency to separate during the
processing, which can result in poor quality product
o Segregation is an undesirable separation of the different components
of a powder mix or blend
o Reasons responsible for de-mixing are;
o The three main mechanisms for segregation of powders are:
move into the voids between larger particles, due to
relatively larger differences in particle size
gradually move under the bigger ones and thus lead to a
separation of the differently sized particles
constantly accelerated and decelerated, due to differences in
trajectories of particles within different masses and /or
sizes these particles will be separated during transportation
heavier particles will roll to the outside of the heap while
the smaller concentrate in the centre of the powder heap
during this type of segregation process
powders by reducing the transportation velocity or minimizing
the falling height to prevent segregation
STEP 6: Mixing Techniques and Equipments (30 minutes)
o Trituration
(comminution) and mixing the powder
o Spatulation
spatula throughout the powders on the sheet of paper
o Sifting
o Geometric dilution
large amounts of diluents
(diluents)
o Geometrically, this will be;
mixture
o Tumbling
rotated by an electric motor (uses a tumble blender)
because of its positive features of close quality control (for
batch operation), effective convective and diffusive mechanisms of
blending and gentle mixing for friable particles
o Particle size
o Shape of the particles
o Density
o Electrostatic forces
o Limits of blend
o Segregation mechanisms
o During powder mixing process, it is important to sample and validate
the adequacy of mixing as a requirement of Good Manufacturing
Practices
o Uniformity of powder blend need formal documentation in a
pharmaceutical manufacturing
o Samples are extracted from a batch or continuous blender to ensure
that the mix meets critical specifications of mixing
o A sample thief (thief sampling) is commonly used to collect powder
sample from a blender or container such as a drum or a bin
receiving powder after being inserted into a powder bed
o Other methods of obtain powder sample can be employed e.g. stratified
(nested) sampling
o Mixing is achieved by use of mixers. Mixers are of various types and
capacities
o Mixers are classified into two main types;
Batch Mixers
o Tumbling mixers
cone Blenders
Static Mixers
Air Mixers
Continuous Mixers
o An ideal mixer should,
damaging the product
o These properties cannot be found in a single mixer and hence selection
of a suitable mixer depends on the following main factors;
➢ Powder characteristics of the constituent of the mixture
➢ Quality requirement of the product
➢ Process requirement and limitations
o Other factors to consider in selecting a mixer are;
➢ Flexibility to cope with variable batch size
➢ Transportability of the mixer between operations like loading,
mixing, packaging
➢ Access to sampling (of powers being mixed)
➢ Frequency of cleaning
➢ Nature of the mixing surface
o Effectiveness of a mixer depends on;
➢ Powders to be mixed
➢ Time of mixing
➢ Number of rotations of the mixer
o Generally, selection of mixers can follow the following approach;
STEP 7: Key Points (5 minutes)
process involving both large and small particle groups and even
individual particles
which involve powder mixing and it has a critical contribution in
achieving uniformity of content
cohesive mixtures and ordered mixtures
capacities
STEP 8: Evaluation (5 minutes)
References
Aulton M.E., & Kevin M.G., Eds: (2013) Pharmaceutics: The design and
manufacture of medicines, (4th ed.) Churchill Livingstone
Hugo and Russell (2011), Pharmaceutical Microbiology (8th ed.) Willey-
Blackwel publications
Gennaro, R. A, et al. (Eds) (1995) Remington: The Science and Practice of
Pharmacy, Volume I & II, (19th ed.): Mack Publishing Company, Easton,
Pennsylvania 18042
Liebsch, B et al (1988). Tanzania Pharmaceutical Handbook, Dar es Salaam
University Press.
Lund, W. Editor (1994). The Pharmaceutical Codex, Principles and Practice
of Pharmaceutics (12th ed.) The Pharmaceutical Press, London
Polderman, J. (1990) Introduction to Pharmaceutical Production: Novib, The
Hague
Rawlins E.A, Editor: (1977) Bentley’s Textbook of Pharmaceutics, (8th ed.)
Baillie're Tindall. London Kamm, G. and Kohler, B. Editors: (1995)
Manual for Decentralized Infusion Production, Infusion Unit Project
Tanzania
Robert EOC, Powders, Remington: the science and practice of pharmacy, vol 2
Schmidt, O. (ed.) 2000 Pharmaceutical Quality systems, Interpharm Press,
Colorado.
Shayne C et al. (2008), Pharmaceutical Manufacturing Handbook: Production
and processes, John Wiley & Sons
Watson, D. G (1999) Pharmaceutical Analysis: A Textbook for Pharmacy
Students and Pharmaceutical Chemists: Churchill Livingstone,
Edinburgh.
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