COPY PASTING ISN'T ALLOWED

1. TOPIC
• EQUIPMENTS USED FOR OINTMENT, PASTE, GELS AND JELLIES
• PACKING OF OINTMENTS

2. CONTENTS:
• Introduction
• Definitions
• Requirements for manufacturing semi solid dosage form
formulations
• Equipment used for manufacturing semi solid dosage forms
• Packaging of ointments

3. INTRODUCTION:
• Semisolid dosage forms are traditionally used for treating topical ailments. Most of them
are meant for skin applications. Semisolids constitute a significant proportion of
pharmaceutical dosage forms.
• They serve as carriers for drugs that are topically delivered by way of the skin, cornea,
rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane, and external ear
lining.
• A semisolid dosage form is advantageous in terms of its easy application, rapid
formulation, and ability to topically deliver a wide variety of drug molecules. Semisolids
are available as a wide range of dosage forms, each having unique characteristics.
• Various categories of drugs such as antibacterial, antifungals, antivirals, antipruritic,
local anesthetics, anti-inflammatory, analgesics, keratolytic, astringents, and mydriatic
agents are incorporated into these products.

4. • Drugs incorporated into semisolids either show their activity on the surface layers of tissues or
penetrate into internal layers to reach the site of action. For example, an antiseptic ointment
should be able to penetrate the skin layers and reach the deep - seated infections in order to
prevent the growth of microbes and heal the wound.
• Topical semi-solid dosage forms are normally presented in the form of creams, gels, ointments, or
pastes. They contain one or more active ingredients dissolved or uniformly dispersed in a suitable
base and any suitable excipients such as emulsifiers, viscosity-increasing agents, antimicrobial
agents, antioxidants, or stabilizing agents.
• Assurance must be provided through product development studies that such excipients do not
adversely affect either the stability of the final product or the availability of the active ingredients
at the site of action; there must be no incompatibility between any of the components of the
dosage form.
INTRODUCTION (conti..):

5. DEFINITIONS OF SEMI SOLID DOSAGE FORMS:
Ointments:
“Ointments are homogeneous, semi-solid preparations intended for external application to the skin
or mucous membranes. They are used as emollients or for the application of active ingredients to
the skin for protective, therapeutic, or prophylactic purposes and where a degree of occlusion is
desired.”
Creams:
“Creams are homogeneous, semi-solid preparations consisting of opaque emulsion systems. Their
consistency and rheological properties depend on the type of emulsion, either water-in-oil (w/o) or
oil-in-water (o/w), and on the nature of the solids in the internal phase.
Creams are intended for application to the skin or certain mucous membranes for protective,
therapeutic, or prophylactic purposes, especially where an occlusive effect is not necessary. The
term "cream" is most frequently used to describe soft, cosmetically acceptable types of
preparations.”

6. Gels:
“Gels are usually homogeneous, clear, semi-solid preparations consisting of a liquid phase
within a three-dimensional polymeric matrix with physical or sometimes chemical cross-
linkage by means of suitable gelling agents and are applied to the skin or certain mucous
membranes for protective, therapeutic, or prophylactic purposes.”
Pastes:
“Pastes are homogeneous, semi-solid preparations containing high concentrations of insoluble
powdered substances (usually not less than 20%) dispersed in a suitable base. The pastes are
usually less greasy, more absorptive, and stiffer in consistency than ointments because of the
large quantity of powdered ingredients present. Some pastes consist of a single phase, such as
hydrated pectin, and others consist of a thick, rigid material that does not flow at body
temperature. The pastes should adhere well to the skin. In many cases they form a protective
film that controls the evaporation of water.”
Jellies:
“Jellies can be defined as semisolid preparations that are transparent, translucent or non-greasy,
intended for internal or external application.”

7. Requirements for manufacturing semi solid dosage form formulations:
The manufacturing processes should meet the requirements of Good Manufacturing
Practice.
The following information is intended to provide very broad guidelines concerning the
main steps to be followed during production, indicating those that are the most important:
• Throughout manufacturing, certain procedures should be validated and monitored by
carrying out appropriate in-process controls.
• They should be designed to guarantee the effectiveness of each stage of production.
Appropriate limits should be set for the particle size of the active ingredient(s), which
should be controlled during production.
• Particular care should be paid to environmental conditions, especially with respect to
microbial and cross-contamination.

8. • Packaging must be adequate to protect topical semi-solid dosage forms from light,
moisture, and damage due to handling and transportation.
• The use of flexible tubes of suitable metal or plastic is preferred. Preparations for
nasal, aural, vaginal, or rectal use should be supplied in containers adapted for
appropriate delivery of the product to the site of application or should be supplied with
a suitable applicator.
Requirements for manufacturing semi solid dosage form formulations:
(Conti...)

9. ORGANOLEPTIC INSPECTION:
Evidence of physical instability is demonstrated by:
• A noticeable change in consistency, such as excessive "bleeding" (separation of excessive amounts of
liquid) or formation of agglomerates and grittiness.
• Discoloration
• Emulsion breakdown
• Crystal growth
• Shrinking due to evaporation of water
• Evidence of microbial growth
• A noticeable change in odor is also a sign of instability.

10. Containers:
The container material should not adversely affect the
quality of the preparation or allow diffusion of any kind
into or across the material of the container into the
preparation. The container should be fitted with a
closure that minimizes microbial contamination and is
equipped with a device that reveals whether the
container has ever been opened.
Uniform consistency:
Topical semi-solid dosage forms
should be of uniform consistency.
When a sample is rubbed on the back
of the hand, no solid components
should be noticed.

11. LABELLING:
Every pharmaceutical preparation must comply with the labelling
requirements established under Good Manufacturing Practice.
The label should include:
(1) The name of the pharmaceutical product
(2) The name(s) of the active ingredient
(3) The amount of the active ingredient(s) in a specified quantity of suitable
base or vehicle, and the quantity of preparation in the container
(4) The batch (lot) number assigned by the manufacturer
(5) The expiry date and, when required, the date of manufacture.
(6) Any special storage conditions or handling precautions that may be
necessary.
(7) Directions for use, warnings, and precautions that may be necessary.
(8) The name and address of the manufacturer or the person responsible for
placing the product on the market.
(9) the name and quantity of antimicrobial agent incorporated in the
preparation.
(10) If applicable, the statement that the preparation is "sterile".

12. Topical semi-solid dosage forms should be kept in well-
closed containers. The preparation should maintain its
pharmaceutical integrity throughout shelf-life when stored
at the temperature indicated on the label and the
temperature should normally not exceed 25 °C.
Storage:

13. Equipment used for manufacturing semi solid dosage forms:
Ointments and Creams:
A wide range of machines are available for the large - scale production of ointments and
creams. Each of these machines is designed to perform certain unit operations, such as
milling, separation, mixing, emulsification, and deaeration. These includes:
• Mills
• Mixers

14. MILLS:
1. Fluidized Energy Mill:
• Fluidized Energy mill, also known as micronize or jet mill is a type of mill that consists of a
hollow toroid that has a diameter of 20-200 mm depending on the height of the loop which can be
up to 2 m. It operates by particle impaction and attrition.
• A fluid or milling gas, usually air or inert gas is injected as a high-pressure jet through nozzles at
the bottom of the loop.
• The powder particles in the mill are accelerated to high velocity. The kinetic energy of the air plus
the turbulence created causes interparticle (particle-particle collision) and particle-wall contact
resulting in particle size between 2 and 10 micrometers. The fluidized effect transports the
particles to a classification zone where the size classifier retains the particles until sufficiently fine
to be removed.

16. Disadvantages:
1. Tendency of forming aggregates or agglomerates after
milling.
2. Generation of amorphous content due to high energy
impact.
3. Formation of ultra-fine particles.
Advantages:
1. The machine has no moving parts and
thus the tendency of contamination due
to wear of parts is minimized.
2. The equipment is easily sterilized.
3. Small particle size (between 2 and 10)
is usually obtained at the end of milling.
4. Thermolabile materials can be milled
with little degradation since the heat
produced by the process is nullified by
the cooling effect of the expansion of
the compressed gas.

17. • Roller mill is a form of compression mill that uses a single, double, or triple
cylindrical heavy wheel mounted horizontally and rotated about their long axis either
in opposing pairs or against flat plates, to crush or grind various materials.
• One of the rollers is run by a motor and the others are rotated by friction as the
material is drawn through the gap between the rollers.
• Roller mills use the process of stress (which is applied by the rotating wheels) and
attrition in milling of solids in suspensions, pastes or ointments, and some solid
materials. The rollers rotate at different speeds and the material is sheared as it passes
through the gap.
2. Roller Mill:

18. Disadvantages:
• Additional operator inputs are required since the rolls need to
be adjusted to suit grind requirements.
Advantages:
• It is employed for preparation of
ointment; paste, creams, and other semi-
solid preparations.
• Less moisture loss
• It is energy efficient/energy saving

19. 3. Colloid Mill:
• Colloid mill is a machine used in the
disintegration of solid particles or droplet size
of a liquid present in suspension or emulsion.
• The machine consists of an inlet (which is
subjected to a tremendous shearing action that
effects a time dispersion of uniform size) and
an outlet.
• Colloid mill works on the rotor-stator principle.
• The equipment breaks down materials by
forming dispersion of materials in a liquid.
Shearing takes place in a narrow gap between a
static cone (the stator) and a rapidly rotating
cone (the rotor).

20. Disadvantages:
1. It has no wide application in solids
2. Wear of the rotating plates
3. No fine grinding
4. Consumes energy though still dependent on some factors.
Advantages:
1. It has a wide range of use including
comminution of slurry- fluid materials.
2. No pressure is required for ionization.
3. The machine is simply constructed.
4. It can be easily adjusted.
5. Colloid mill is easy to clean after use
6. The machine is self-draining.
7. High capacity and minimal
requirements.

21. Mixers:
1. Planetary Mixer:
The mechanism of mixing is shear. It imparts
planetary mixing action, in which mixing element
rotates round the circumference of the mixer’s
container, while continuous rotating about its own
axis. The double rotation of the mixing element and
its offset position reduces the dead zones and avoids
vortex formation. Planetary mixers are mainly used
to mix medium viscous to high viscous media.

22. 2. Sigma-Blade Mixer:
Sigma-blade mixer has counter-rotating blades or
heavy arms that work the plastic mass. The two
sigma shaped blades which sit horizontally and
parallel at the bottom of the mixing trough rotates
in opposite directions at different speeds. The
blades rotates tangentially with a speed ratio of
about 2:1. Shear forces are generated by the high
viscosity of mass and are effective in de-
aggregation as well as distribution of solids in the
fluid vehicle.

23. 3. Muller Mixer:
Mulling mixers provide forces that incorporate
kneading, shearing, smearing and blending of
materials of materials for a total uniform
consistency. Mulling is an extension of mixing
resulting from the intensification of work forces.
Moreover, mulling mixers are efficient in de-
aggregation of solids but not provide uniform
distribution of particles. They are employed for
mixing of previously mixed materials for uniform
composition.

24. Equipment for Gels, Jellies and Pastes:
The equipment described before are employed for
manufacturing for these semi solid dosage forms as
well. But there are some specific equipment that are
used for gels and pastes.
Pharmaceutical Tube Filling Equipment:
Tube and cream fillers are often used in the
pharmaceutical industry to provide precision tube
filling and sealing of plastic and plastic/laminate
tubes with high quality output. Depending on the type
of machinery, tube and cream filler can handle
viscous, semi-viscous and liquid products - including
paste, ointment, lotion, topical, moisturizers,
conditioners, and other chemical and foodstuff
products. The tube filling and closing system is suited
for the dosing of liquids in a filling range from 50 to
5000 ml.

25. Homogenization requires the ingredients to be processed until a uniform globule or particle size. They are
used for pastes, creams, ointments, sauces, flavoring emulsions and pharmaceutical suspensions, this requires
a globule or droplet size in the range of 2 – 5 microns. This can be achieved using a silver-son mixing
homogenizer.
This generates exceptionally high shear rates in a three-stage mixing/homogenizing process:
• The high-speed rotor draws materials into the work head where they are intensely mixed. Centrifugal force
then drives the materials to the periphery of the work head and subjects them to mechanical shear in the
precision gap between the rotor and stator.
• This is followed by intense hydraulic shear, as the product is forced through the stator screen at high
velocity and circulated back into the mix.
• Fresh material is continually drawn into the work head, progressively reducing globule or particle size and
quickly resulting in a homogeneous, uniform product.
Homogenizers

26. PACKAGING OF OINTMENTS:
The USP recommends packaging and storage requirements for
each official ointment. These includes:
Tubes:
• As tubes made of aluminum and plastic meet most of these
qualities, they are extensively used for packaging semisolids
including ointments.
• Aluminum tubes with special internal epoxy coatings are
commercially available for improving the compatibility and
stability of products.
• Various modified plastic materials are used for making
ointment tubes. Tubes made of low - density polyethylene
(LDPE) are generally soft and flexible and offer good moisture
protection. Tubes made of high - density polyethylene (HDPE)
are relatively harder but offer high moisture protection.

27. Containers
Polypropylene containers offer high heat
resistance.
Plastic containers made of polyethylene
terephthalate (PET) are transparent and provide
superior chemical compatibility.

28. IMPORTANT
FACTORS TO BE
CONSIDERED FOR
MANUFACTURING
SEMI SOLID
DOSAGE FORM AT
LARGE SCALE:
1. Material transfer rate.
2. Mixing.
3. Heating.
4. Viscous and Non-Newtonian Liquids.
5. Equipment for Non-Newtonian Materials in Semi
Solid Dosage forms.

29. • Transfer of semisolids from one location (production tank) to another location (filling
tank) is achieved through pipes by inducing flow with the aid of pumps.
• Induction of flow occurs by one or more mechanisms, including gravity,
electromagnetic force, mechanical impulse, centrifugal force, displacement, or
momentum transfer.
• Materials transfer during mixing can occur by two mechanisms, either diffusion or
bulk flow. Bulk flow involves motion induced either artificially by mechanical
agitation or naturally by density variation. Diffusion involves the movement of heat or
mass from a region of higher concentration to the region of lower concentration.
1. Material Transfer Rate

30. 2. Mixing:
• Semisolids are prepared by mixing the aqueous and
the oily phase in mixing tanks with different designs
of impellers. Generally, to prepare semisolids
preparations like ointments and creams, either agitator
mixers or shear mixers are used.
• Mixing is one common step involved in the
preparation of semisolids. While considering mixing
of discontinuous phase with the continuous phase, one
needs to determine the optimum amount of shear and
optimal mixing methods and whether the speed is
sufficient to obtain a uniform semisolid product at
larger scale.
• Creams (o/w emulsions or w/o emulsions) require
higher shear to obtain uniform droplet size and
dispersion. On the contrary, gel requires low shear to
preserve physical characteristics such as viscosity.
Thus, mixing speed needs to be optimized at each
batch scale.

31. 3. Heating and Cooling Rates:
• Semisolids have the property of melting at a moderate temperature and solidifying if cooled at room
temperature.
• Semisolid preparations involve phase transition in which melting results in an absorption of the heat
and cooling which releases heat.
• Cooling rates have a significant effect on the initial as well as the final consistency of creams
prepared with fatty alcohol or nonionic polyoxyethylene surfactants. Sudden cooling of emulsion
creams result in a very mobile emulsion which tends be converted to a gel on storage.

32. • 4. Viscous and Non-Newtonian
Liquids:
• Viscous liquid generally shows a
tendency to undergo improper mixing
by conventional impellers. Non-
Newtonian liquids exhibit variability in
the viscosity due to the shear imparted
by the impeller. This gradual change in
viscosity affects the mixing efficiency.
• The paddles, anchors, screws, and
kneading mixers are used in order to
increase in the viscosity. The Z blade or
sigma blades are specialized impellers
used to promote mixing in the region
closer to the wall of the mixing tank
along with the narrow clearance
between the impeller blades and the
wall of the mixing tank to obtain
maximum mixing efficiency.

33. 5. Equipment for Non-Newtonian
Materials in Semi Solid Dosage
forms:
Equipment’s used for non-Newtonian
materials in semisolids preparation:
• Helical ribbon impeller is used for
designing plastic and pseudoplastic
materials.
• Double planetary mixers are used
for dilatant materials comprised of
any one of the three types of blades
to provide sufficient torque for
uniform dispersions of materials, the
viscosity of which tends to increase
with the increase in the shearing
stress.

34. REFERENCES:
1. The International Pharmacopoeia - Ninth Edition. Topical semi-solid dosage forms 2020 [cited 2020 15 December].
Available from: https://apps.who.int/phint/pdf/b/6.2.1.8.Topical-semi-solid-dosage-forms.pdf.
2. Maqbool MA, Mishra MK, Pathak S, Kesharwani A, Kesharwani A. Semi solid dosage forms manufacturing: Tools,
critical process parameters, strategies, optimization and recent advances. Indo Am J Pharm Res. 2017;7:882-93.
3. Gad SC. Pharmaceutical manufacturing handbook: production and processes: John Wiley & Sons; 2008.
4. Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial pharmacy: Lea & Febiger; 1986.
5. Approach P. Equipments 2020 [cited 2020 15 December ]. Available from: https://www.pharmapproach.com/.
6. Raval N, Tambe V, Maheshwari R, Deb PK, Tekade RK. Scale-up studies in pharmaceutical products development.
Dosage Form Design Considerations: Elsevier; 2018. p. 669-700.
7. Review AP. Pharmaceutical Tube Filling Machine 2020 [cited 2020 16 December ]. Available from:
https://www.americanpharmaceuticalreview.com/25310-Pharmaceutical-Manufacturing/25349-Pharmaceutical-Tube-
Filling-Machine-Cream-Filling-Machine-Paste-Cream/.