1. FORMULATION DEVELOPMENTFORMULATION DEVELOPMENT
OF SEMISOLID DOSAGEOF SEMISOLID DOSAGE
FORMSFORMS
PRESENTED BY
B.SUNIL KUMAR REDDY
M.PHARMACY

3. INDUSTRIALINDUSTRIAL
PROCESSINGPROCESSING

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. IDEAL PROPERTIES OF SEMISOLIDS PHYSICAL PROPERTIES
Smooth texture
Non dehydrating
Non gritty and non greasy
Elegant in appearance

6. PHYSIOLOGICAL PROPERTIES
Non irritating
Do not alter membrane or skin functioning
Miscible with skin secretion
APPLICATION PROPERTIES
 Easily applicable with efficient drug release.
High aqueous wash ability.

7. Types of semisolidTypes of semisolid
basesbases
The ointment base is the substance or part of
ointment, which serves as carrier or vehicle for the
medicament. Ointment
bases are of following types
A) Oleaginous bases or Hydrocarbon base
Ex. Hard paraffin, Yellow soft paraffin.
B) Absorbent base
Ex. Hydrous wool fat, lanolin
C) Emulsion bases or water miscible bases
D) Water soluble bases
Ex. PEG, Polysorbate

8. FORMULATION:FORMULATION:
1)Hydro carbons: Petrolatum and mineral oil are
the most widely used substances in semisolids
 Petrolatum is a complex mixture of semisolid
hydrocarbons, containing aliphatic, cyclic,
saturated, unsaturated, branched and
unbranched substances in varying proportions.
Petrolatum is available in the form of a short or
long fiber.
Mineral oil is obtained from petrolatum, by
collection of a particular viscosity-controlled
faction.

9.  It is produced in many viscosity and specific gravity
ranges.
 The lower viscosity oils are preferred for
semisolids, since they are less tacky and greasy.
2)Hydrocarbon waxes: These waxes are frequently
employed in the manufacture of Creams and
ointments to increase the viscosity of mineral oil in
order to prevent its separation from an ointment

10.  Paraffin wax is obtained from petrolatum and available
in variety of melting points ranging from 35 to 75°C.
 Ozokerite is a mined wax with a melting point range of
65 to75°C.
 Synthetic waxes have been developed from vegetable
oils and naturally occurring waxes by a process of
hydrogenation and catalytic splitting.
 Synthetic waxes are chemically closely related to the
naturally occurring waxes in that they contain long
chain wax fatty acids, but are not considered to be
direct replacements for them.

11. 3)Oleaginous substances: vegetable oils such as peanut
oil, almond oil and olive oil are mono, di, and tri
glycerides of mixtures of unsaturated and saturated
fatty acids.
4)Fatty acids & alcohols: The commercially available fatty
acids are stearic acid and palmitic acid.
 Stearic acid is used in water-removable creams as an
emulsifier to develop a certain consistency in the cream
and to give a matt effect on the skin.

12. 5) Emulsifiers: The water-soluble soaps were among the
first emulsifiers used for semisolid oil-in-water
emulsions.
 Nearly all semisolid creams and emulsified ointments
require more than one emulsifier.
 The combination of a surface active agent with an oil-
soluble auxiliary emulsifier is referred to as a mixed
emulsifier system.

13. 6) Polyols: Glycerine, propylene glycol, sorbitol 70%
and the low molecular weight polyethylene glycols are
used as humectants in creams.
 These materials prevent the cream from drying out
and prevent the formation of a crust when the cream
is packaged in a jar.

14. 7)Insoluble powders: Insoluble drugs must be uniformly
dispersed throughout the vehicle to ensure homogeneity
of the product.
 Milling of a drug to a finely divided state provides more
surface area for contact with the dermal site and
increases the rate of dissolution of poorly soluble
substances.

15. PASTES,GELS AND JELLIES :PASTES,GELS AND JELLIES :
 Pastes are dispersions of high concentrations of
insoluble powdered substances(20 to 50%) in a fatty or
aqueous base.
 The fatty bases are less greasy as well as stiffer in
consistency than ointments because of the large amount
of powdered material present.
 Jellies are water-soluble bases prepared from natural
gums such as tragacanth, pectin and alginates.

16.  Gels are usually clear transparent semisolids containing
the solubilized active substances like
hydroxypropylcellulose and hydroxy
propylmethylcellulose.
OPHTHALMIC OINTMENTS:-
 Semisolid ophthalmic vehicles contain soft petrolatum,
an absorption base or a water soluble base.

17.  All materials used in the ophthalmic ointment should be
impalpable to avoid eye discomfort and possible
irritation.
PRESERVATION FROM MICROBIAL SPOILAGE:
 Chemical preservatives for semisolids must be
carefully evaluated for their stability with regard to
the other components of the formulation as well as to
the container.

18.  Plastic containers may absorb the preservative and there
by decrease the quantity available for inhibiting or
destroying the micro organisms responsible for spoilage.
 The preservatives are added to semisolids to prevent
contamination, deterioration and spoilage by bacteria and
fungi, since many of the components in these preparations
serve as substrates for these microorganisms.

19.  The paraben esters of p-hydroxy benzoic acid is popular
as preservative because their toxicity is low, odorless &
non irritating to the skin.
 ANTIOXIDANTS:- These are added to semi solids when
ever oxidative deterioration is anticipated.

20. PREPARATION OF SEMI SOLIDSPREPARATION OF SEMI SOLIDS
Trituration
method
Fusion
method
Chemical
reaction
method
Emulsificatio
n method
Ex. Ointments
creams
pastes
Ex. Ointments
creams
pastes
Ex. Ointments
creams
Ex. Ointments
creams
(Ointments, creams, pastes)

21. PREPARATION METHODS FORPREPARATION METHODS FOR
SUPPOSITORIESSUPPOSITORIES
Hand molding Heat molding
Automatic
machine
molding
Compression
molding
Ex. Rotary machine
linear machine

22.  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.

23.  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.

24.  Aeration should be avoided, since it may lead to emulsion
instability and variation in density with in a batch.
 Entrainment can occur
1. Homogenizing
2. Milling stage
3. Filling equipment
4. Packaging operation.

25.  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.

26. Rheological changes:Rheological changes:
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.

27. HOMOGENIZERSHOMOGENIZERS::
For homogenization colloidal mill is used.
Colloidal mill:It consists of two steel discs one is
stationary and other is rotating.when the material is
passed through these discs they get sheared.
Thus,coarse particles are broken down to small
particles due to shear.
Uses: Used for preparation of suspensions,ointments.
Advantage:It can be easily sterilised.
Disadvantage:Heat is generated during milling.

28. Fusion method:
Anhydrous ointments are prepared by fusion
method.
Active substances is dissolved in the melted fats
and waxes and then mixed with base. The melted
mass must mixed while cooling because the fatty
alcohols, fatty acids, and waxes do not form true
solutions, but crystallize from the melt as the
temperature falls.

29. Manufacture of emulsions:
Time, temperature and mechanical work are the
three variables in the manufacture of emulsified
semisolids. The three factors are interrelated and
must be carefully controlled if the same high
quality batches are to manufactured.
Equipment is available for automatically controlling
many aspects of emulsion manufacture, such as the
complete control of the temperature in the jacket
and regulation of the mixing time and rate of
agitation.

30. PREPARATION OF OIL AND
AQUEOUS PHASES

31.  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.

32.  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.

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

34.  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

35. 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.

36.  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.

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

38. 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:Sigma blade mixer:

40. 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:

42.  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 SEMISOLIDCOOLING THE SEMISOLID
EMULSION:EMULSION:

43.  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.

44. 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.

45.  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.

46. 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.

47.  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.

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