MIXING
BY
MS. FATHIMA NASREEN FAKRUDEEN.,MPHARM
The term mixing is defined as a process that results in randomization of dissimilar
particles within a system. Mixing is defined as an operation in which two or more
components in a separate roughly mixed condition are treated so that each particle
lies as nearly as possible in contact with a particle of each of the other ingredient.
Mixing may be performed between any two phases ranging from mobile liquids to
viscous liquids, semi-solids and solids.
The operation opposite to the mixing is ‘segregation’. The terms ‘mixing’ and
‘blending’ are often used synonymously, but technically they are a bit different.
Mixing and blending are the most demanding unit operations in the pharmaceutical,
chemical and food process industries. For example, chemical process industries
involves mixing and blending of specialty chemicals, explosives, fertilizers, dry
powdered detergents, glass or ceramics, and rubber compounds.
Pharmaceutical industry employs blending of active ingredients of a drug with
excipients like starch, cellulose, or lactose whereas in food industry preparation of
cake mix, spices, and flavours.
Generally mixing can lead to three types of mixtures that are fundamentally
different in their behaviours:
(i) Positive mixtures:
Positive mixtures formed when two or more components are irreversibly mixed
together by diffusion process. In this case no energy input is required and the time
allowed for the components to mix is sufficient. In addition, these types of materials
do not create any problem during their mixing process.
(ii) Negative mixtures:
Negative mixtures are formed when components are mixed to form a heterogeneous
system, for example, emulsion or suspension. The components of these mixtures have
high tendency to separate out as they are not continuously being stirred. Thus, such
mixtures are more difficult to prepare as they need high degree of mixing with
external force.
(iii) Neutral mixtures:
Neutral mixtures are stable in behavior. The components of these mixtures do not
have tendency to mix spontaneously but once mixed, they do not separate out easily.
Pharmaceutical products such as pastes, ointments and mixed powders are the
examples of neutral mixture.
OBJECTIVES
(i) To produce single physical mixture
(ii) To produce physical change
(iii) To produce dispersion
(iv) To promote chemical reaction
APPLICATIONS
Dry mixing:
Mixing help various powders to be mixed in varying proportions prior
to granulation or tableting. Dry mixing of the materials makes them suitable for
direct compression in to tablets.
Product features:
The mixing help to deliver accurate dosage that has an
acceptable appearance and texture, or to maintain formulation stable for the
appropriate length of time. The importance of proper mixer selection and its
optimal operation can hardly be over-estimated.
Dry blending:
Mixing is used for dry blending in the manufacture of many vitamins,
dietary supplements and drugs in powders (insufflations, face powders, and tooth
powders), capsules and tablets. Dry blending operation combines the active
ingredient with other solid excipients in most appropriate way.
Sometimes relatively small amounts of liquid may be added to the solids in
order to coat or absorb colouring and flavouring agents, oils or other solutions.
Emulsions:
Throughout the pharmaceutical industry, high shear mixing is widely used in the
preparation of emulsions such as creams and medicated lotions.
Heterogeneous mixtures:
Mixing is used when different powders behave differently when added into liquid,
and some require more coaxing in order to dissolve, hydrate or disperse completely
than others. The ‘easier’ ones need only gentle agitation but more challenging
powders needs higher speed devices that generate a powerful vortex into which the
powders are added for faster wet-out.
Tough agglomerates:
It is used to deal solids that tend to form tough agglomerates which do not easily
break apart. A high shear mixer is often used to resolve such issues and many
solutions and dispersions are made. For example, tablet coatings, vaccines and
disinfectants.
Fluid blending:
Mixing is used for continuous blending of fluid streams, emulsification, and
dispersion of gases into liquid, pH control, dilution and heat exchange. A static
mixer is unique with no moving part that relies on external pumps to move the
fluids through it. For example, dissolution of soluble solids in viscous liquids for
dispensing in soft capsules and in the preparation of syrups.
Viscous fluids:
Mixing is used for batch mixing of viscous formulations. Mixers are used in the
pharmaceutical industry for batch manufacturing of moderate to relatively high
viscosity applications such as syrups, suspensions, pastes, creams, ointments and
gels.
Uniformity in size distribution:
Mixing helps in particle size distribution and other related parameters which
depends on cycle time and mixer design. Thus selection of proper mixer along with
product chemistry, operating temperature, pressure/vacuum conditions, quality of
raw materials, presence of additives etc. help to obtain appropriate product features.
FACTORS AFFECTING MIXING
Material density
Particle size
Particle shapes
Particle attraction
Proportion of materials
Mixer volume
Mixing mechanisms
Mixing time
Method of handling
Nature of the product
Mixing Conditions
