Another problem associated with liquid

drugs is that those intended for oral administration

cannot generally be formulated
into tablet form, the most popular form of
oral medication, without chemical modification.

Liquid drugs pose an interesting problem

in the design of dosage forms and
delivery systems. Many liquids are volatile
and must be physically sealed from the
atmosphere to prevent evaporation loss.

Formulation and stability difficulties arise

less frequently with solid dosage forms than
with liquid preparations, and for this reason,
many new drugs first reach the market
as tablets or dry-filled capsules.

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In
the preparation of tablets, diluents or fillers
are commonly added to increase the bulk of
the formulation, binders to cause adhesion
of the powdered drug and pharmaceutical
substances, antiadherents or lubricants to
assist smooth tablet formation, disintegrating
agents to promote tablet breakup after
administration, and coatings to improve
stability, control disintegration, or enhance
appearance.

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As mentioned above, many properties other than

rate of solution can change when a material is in a
different polymorphic form. For example, paracetamol
is a high-dose drug with poor compression
properties, which can make it difficult to form into
tablets. Consequently, researchers have tried to use
different polymorphic forms of paracetamol to find
one that is more compressible.

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Some materials, e.g. paracetamol, are elastic and

there is very little permanent change (either plastic
flow or fragmentation) caused by compression: the
material rebounds (recovers elastically) when the
compression load is released. If bonding is weak the
compact will self-destruct and the top will detach
(capping), or the whole cylinder cracks into horizontal
layers (lamination). An elastic body will give as
follows:

A will cap or laminate.

B will probably maintain integrity but will be very
weak,
C will cap or laminate.
Elastic materials require a particularly plastic tableting
matrix or wet massing to induce plasticity.

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Wet granulation involves the massing of a mix of

dry primary powder particles using a granulating
fluid. The fluid contains a solvent which must be
volatile so that it can be removed by drying, and be
non-toxic. Typical liquids include water, ethanol and
isopropanol, either alone or in combination. The
granulation liquid may be used alone or, more
usually, as a solvent containing a dissolved adhesive
(also referred to as a binder or binding agent}
which is used to ensure particle adhesion once the
granule is dry.
Water is commonly used for economical and
ecological reasons. Its disadvantages as a solvent are
that it may adversely affect drug stability, causing
hydrolysis of susceptible products, and it needs a
longer drying time than do organic solvents. This
increases the length of the process and again may
affect stability because of the extended exposure to
heat. The primary advantage of water is that it is
non-flammable, which means that expensive safety
precautions such as the use of flameproof equipment
need not be taken. Organic solvents are used when

water-sensitive drugs are processed, as an alternative

to dry granulation, or when a rapid drying time is
required.
In the traditional wet granulation method the wet
mass is forced through a sieve to produce wet granules
which are then dried. A subsequent screening
stage breaks agglomerates of granules and removes
the fine material, which can than be recycled.
Variations of this traditional method depend on the
equipment used, but the general principle of initial
particle aggregation using a liquid remains in all of
the processes.

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Lactose USP, anhydrous offers most of the advantages of lactose USP,
hydrous. without the reactivity of the Maillard reaction. which leads to
browning. Tablets generally show fast disintegration. good friability. and
low weight variation. with an absence of sticking, binding. and capping.
The applications of the anhydrous form have recently been evaluated by a
number of investigators (36- 39]. Mendell [40] has reported on the relative
sensitivity of lactose to moisture pickup at elevated humidities. Blister
packages should be tested at elevated temperatures and humidity to establish
their accept ability with lactose- based formulas.

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Usually, fine grades of lactose are used in the preparation of tablets

by the wet-granulation method or when milling during processing is
carried out, since the fine size allows better mixing with other
formulation ingredients and utilizes the binder more efficiently.

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