Lecture 6

Production troubleshooting of molded

Solid/Semi-solid dosage forms

DR. YASMINE SAMAK, PHD

LECTURER OF
PHARMACEUTICS
General troubleshooting guide
Splitting, pitting and cracking
Suppository production methods
*Fusion molding*
 Splitting, pitting and cracking

Causes Remedies
Excipient contracts Use an excipient that
strongly crystallizes more slowly

Too great a difference Reduce the differential

between the be either dropping the
temperatures of pouring pouring temperature (if
and cooling possible) or increasing
the cooling temperature,
or both
 Sticking to mold
Causes Remedies
Improper molds Use appropriate equipment

Premature removal Prolong molding period

from mold

Excipient contracts Use an excipient that

weakly crystallizes more rapidly

Insufficient cooling Reduce cooling

temperature
 Thickening prior to pouring

Causes Remedies
Solid active ingredients Use a mass containing
that partially solubilize in an anti-crystallizing
the excipient with time. agent.

High proportion of finely

powdered active
ingredients.
 Poor product homogeneity

Causes Remedies
Insufficient stirring Improve technique

Pouring temperature Reduce temperature (if

too high possible)

Cooling too slow or Increase cooling (if

too weak possible)
 Product insufficiently solid

Causes Remedies
Inclusion of air Check the stirring level and
type

Improper excipient Use an excipient that has a

high mechanical resistance
.Surface anomalies (fat bloom or whitening)
.Exudation
Causes Remedies

Excipient melting at Reduce melting temperature

more than 60C
Check behavior of active
ingredient

Incorrect Reformulate aqueous solutions

excipient/active ratio
Use an excipient containing an
emulsifier
 PRODUCTION
TROUBLESHOOTING OF
PHARMACEUTICAL CREAMS
AND OINTMENTS
Production of pharmaceutical creams &
ointments

Pharmaceutical preparations for treatment of conditions

such as rashes, skin irritation, stings, fungal infections
etc. are normally supplied in the form of a cream or
ointment as this provides an effective means of
delivering the active ingredient directly on the required
area. Products can be either a water in oil (w/o) or oil in
water (o/w) emulsion, consisting of waxes, emollients
and lubricants dispersed in an oil phase, and a water
phase containing emulsifying, stabilizing and thickening
agents, preservatives and in some cases, colorant. Active
ingredients are dispersed in either phase or added when
the emulsion has been formed and allowed to cool.
 Production of pharmaceutical creams
& ointments

Products can be either a water in oil (w/o) or oil in water (o/w) emulsion

+
Active
ingredients

Oil phase Aqueous phase

Waxes Emollients Lubricants Emulsifying Stabilizing Thickening Preservatives

agents agents agents
 The process:

Ingredients, formulation and product viscosity differ

widely, however, a typical manufacturing process
breaks down into four individual operations:

Preparation of the oil phase.

Hydration of aqueous phase ingredients.
Forming the emulsion.
Dispersion of the active ingredients.
Using conventional agitators a number of
problems can be encountered:
Using conventional agitators a number of problems
can be encountered:

When added to water, thickening, stabilizing and

emulsifying agents can form agglomerates which
agitator cannot break down.

Similarly oil phase ingredients can form lumps which

require shear to disperse.

Ingredients must be fully hydrated to obtain the

required viscosity and develop yield.
Using conventional agitators a number of problems
can be encountered:

Partially hydrated materials can build up on the vessel wall, in-

tank baffles and parts of the agitator.

Agitators can not sufficiently reduce droplet size to form a stable

emulsion.

Active ingredients can be temperature sensitive. Cooling of the

product before adding the active ingredient further increases
processing time.

Poor dispersion of the active impairs product effectiveness.

Long mixing times and additional equipment may be required to

obtain a homogeneous and stable finished product.
Solution:

A Silverson mixer (based on rotor/stator principle)

Can rapidly disperse solids into liquids, hydrate
thickening and stabilizing agents, break down
agglomerates, and finely reduce particle and globule
size to form stable emulsions and suspensions.

Mixing times are dramatically reduced, while product

uniformity and consistency are greatly improved.
Silverson mixer
The Advantages:

Stable emulsion.
Agglomerates-free mix.
Dramatically reduced mixing time.
Maximized yield of raw materials as thickening agents are
fully hydrated and other ingredients fully dispersed.
In-tank baffles are not required, improving vessel hygiene.
Pre-mixing of powdered ingredients can be eliminated.
The aqueous phase can be produced at ambient
temperatures, reducing heating costs. This also accelerates
cooling of the mixture, further reducing process time and
costs.
Consistent product quality and repeatability.
 Video:

http://www.silverson.com/us/resource-
library/videos/deagglomeration-us