This document discusses the formulation development process for semisolid dosage forms. It covers topics such as preparing the oil and aqueous phases, mixing the phases using different equipment like sigma mixers and colloidal mills, cooling the emulsion, adding perfumes and drugs, storing the product, and transferring it for packaging. Maintaining sterile conditions during manufacturing and packaging is also emphasized.

1. FORMULATION DEVELOPMENT
OF SEMISOLID DOSAGE
FORMS
PRESENTED BY
B.SUNIL KUMAR REDDY
M.PHARMACY

3. INDUSTRIAL PROCESSING

4. Semisolid dosage forms are
dermatological preparations intended to
apply externally on the skin to produce
local or systemic effect.
Ex: Ointments, creams, pastes,
gels etc
Definition:

5.  Pilot plant or small scale production equipment is
essential in developing a manufacturing procedure for a
production size batch.
 The preparation of many batches ranging in size from 2.5
to 25 or more kilograms, for product evaluation and clinical
testing provides opportunity to observe, improve and
correct the variations.
 Mixing and stirring operations are critical in the
preparation these can be controlled in 0.5- 1.0kg batches of
finished product.

6.  The electrically operated propeller type mixer can
be manually adjusted and positioned in the laboratory
mixing vessel to achieve maximum turbulence.
 The angle of entry of the propeller shaft and the
depth of the propeller can be easily varied in the
laboratory to prevent aeration.
 A metal spatula can be held or positioned in the
beaker during mixing to serve as a baffle to increase
turbulence with out entrainment of air.

7.  Aeration should be avoided, since it may lead to
emulsion instability and variation in density with in a
batch.
 Entrainment can occur
 Homogenizing
 Milling stage
 Filling equipment
 Packaging operation.

8.  Aeration maybe prevented at the primary emulsion
step if one phase is introduced into the other in such
a manner that splashing and streaming are avoided.
 Splashing can overcome by careful adjustment of the
mixing conditions and liquid flow pattern.
 Completely enclosed kettles are available for the
manufacturing of semisolids which tend to aerate
excessively.

9. Homogenization frequently increases the
consistency of a semisolid emulsion because it
increases the number of emulsified particles.
consistency is affected by
1. Number of passes through the homogenizer.
2. Pressures used for homogenization.
Rheological changes:

10. PREPARATION OF OIL AND
AQUEOUS PHASES

11.  The components of the oil mixtures are placed into a
stainless steel steam jacketed kettle,melted and
mixed.
 Some of the solid components e.g. stearic acid,cetyl
alchol are available in many different forms like
cakes,flakes or powder. The flakes are more
preferable because of the convenience of handling.
 Petrolatum is inconvenient to handle unless it is
melted and transferred by pumping or pouring from
its drum.

12.  The oil phase is then strained through several layers
of cheese cloth to remove any foreign matter.
 If petrolatum is used as oil phase then it should be
passed through filter medium particularly in
ophthalmic preparations.
 The oil phase is transferred by gravity or pump to
the emulsion mixing kettle.

13.  The components of the aqueous phase are dissolved in
the purified water and filtered.
 A soluble drug may be added to this aqueous phase.

14.  The phases are usually mixed at a temperature of 70
to 720
C,because at this temperature intimate mixing
of the liquid phases can occur.
 The properties of some emulsions depend on the
temperature at which the phases are mixed.The
initial mixing temperature must be raised above 70 to
72 0
C.
MIXING OF PHASES

15. Three ways of mixing the phases:
1.Simultaneous blending of the phases.
2.Addition of the discontinuous phase to the continuous phase.
3.Additon of the continuous phase to the discontinuous phase.

16.  The simultaneous blending of the phases requires the
use of a proportioning pump and a continuous mixer.
 This method is used for continuous or large batch
operation.
 The second method is used for emulsion systems that
have a low volume of dispersed phase.
 The third process is preferred for many emulsion
systems.

17. Equipments used for mixing of phases:
1. Agitator mixers :Sigma mixer and planetary mixer.
2. Shear mixers: Triple roller mill and Colloidal mill.

18. The mechanism of mixing is shearing.The sigma shaped
blades creates high shear.
Advantages:
1.It creates a minimum dead space during mixing.
2.It is used for wet granulation process.
Disadvantages:
1.It works at a fixed speed.
Sigma blade mixer:

20. It consists of two steel discs.Here one disc rotates and another one
is stationary. When the material is passed through these discs
they get sheared.Thus coarse particles are break down to small
particles due to shear.
Advantages:
1.It can be used in the production of sterile products.
Disadvantages:
1.It is not used for dry milling.
2.Heat is generated during milling.
Colloidal mill:Colloidal mill:

22.  The rate of cooling is generally slow to allow for adequate
mixing while the emulsion is still liquid.
 The temperature of the cooling medium in the equipment
should be decreased gradually and at a rate consistent with
the mixing of the emulsion and scrapping of the kettle walls
to prevent formation of congealed masses of the ointment or
cream.
COOLING THE SEMISOLID
EMULSION:

23.  Perfume should be added at 43 to 450
c to avoid
chilling the emulsion in case of oil in water type
emulsion.
 Perfume should be added at room temperature in
water in oil type emulsion.
 If the drug is not added in the aqueous phase then it
should be added in solution form or in the form of
crystals.

24. STORAGE OF SEMI-SOLIDS
 Unless rapid in process methods of analysis are
developed, it is the usual practice to store the
semisolid until the specified quality control tests have
been completed before packaging into appropriate.
containers: tubes, jars, or single dose packets.
 A product is considered to be in process until it has
been packaged.

25.  Evaporation of water from a cream must be
retarded; this can be effectively accomplished by
placing non-reactive plastic sheeting in direct contact
with the cream, as well as covering the storage
container with a tight-fitting stainless steel lid.
The active substance in the cream or ointment
may react with the storage container unless a
Highly resistant, stainless steel, is used for bulk
storage.

26. TRANSFER OF MATERIAL FOR
PACKAGING
 The semi-solid may be gravity fed, if it is a two-Level
operation or pumped to the filling equipment.
 It must be able to resist the shear stress developed
in the transfer of the product, as well as that due to
the mechanical action of the filling equipment.
 Once a formal manufacturing procedure has been
established, there should be no deviation from it.
The manufacturing and packaging equipment should be
sanitized following thorough cleaning with detergents.

27.  They should be flushed with chlorinated water,
formalin, or other suitable sterilant followed by a
bacteria-free water rinse.
 Water and swab samples should be taken to verify
microbial elimination.