Transcript Semisolid dosage forms. Ointments production in the industrial conditions. Equipments.

Theme of lecture:
Semisolid dosage forms.
Ointments production in the
industrial conditions.
Equipments.
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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 to the
required area.
Semisolid dosage forms are designed for topic
application, for treatment wounds and certain
mucous membranes. They have the local
therapeutic emollient or protective action, or for
the drugs penetration through the skin or
mucous membranes.
They are characterized by:
 specific rheological properties at certain
temperature of storage
 non-Newtonian type flow
 certain structural viscosity
 pseudoplastic or plastic and thixotropic
Positive aspects of
semisolid dosage forms:
1. they have a local effect, resorptive activity and
provide of a high concentration of medicines in the
skin, tissues, in biological fluids and organs of the
body;
2. they are the best dosage form for treatment of
infected wounds, burns, dermatitis of various
etiologies, frostbite, diaper rash, bed sores;
3. ointments may contain substances which are
different to the mechanism and direction of medical
action;
Positive aspects of
semisolid dosage forms:
4. ointments can be used for general effect on the
body or selective for certain organs or body
systems, such as an ointment "Nitrong", which is
used to prevent strokes;
5. the possibility of achieving a high therapeutic effect
of ointments due to the concentration of drug
substances and due to optimum selection and
combination of drugs and excipients;
6. relative ease and safety application of the
ointments.
Negative aspects of soft dosage forms:
1. several ointments have limited therapeutic
efficacy becouse their inherent unidirectional
effect on symptoms;
2. some ointments contain in their composition
unstable, ineffective substance or substances
which are difficult to standardize;
3. separate formulations of ointments, produced
on a hydrophobic basis, cause a pronounced
"greenhouse" effect.
Classification of the semisolid drugs
and bases:
1. for its affinity to water:
- hydrophilic
- hydrophobic (lipophilic);
2. for its ability to absorb water and the mechanism of
absorption;
3. for the type of disperse systems:
- single-phase (solutions, alloys),
- two-phase (emulsion, suspensions)
- multiphase systems;
4. for its rheological properties at fixed temperature and
storage conditions;
5. for the concentration and dispersion of the excipients and
/or drugs.
Classification semisolid drug depend on
the aggregate state:
• Ointment (Ointments)
• Creams (Creams)
• Gels (Gels)
• Paste (Pastes)
• Liniments (Liniments)
Ointments - semisolid dosage forms for local
use, a dispersion medium which has a nonNewtonian type of flow and high values of
rheological parameters in the set temperature of
storage.
Creams - semisolid dosage forms for local use,
representing two-or multi-phase dispersions, a
dispersion medium which usually has a nonNewtonian type flow and low values of
rheological parameters in the set temperature
of storage.
Gels - semisolid dosage forms for local use,
representing one-, two-or multiphase disperse
systems with a liquid dispersion medium, the
rheological properties of which are caused by the
presence of gelling agent in relatively low
concentrations.
Paste - semisolid dosage forms for local use,
which is a suspension containing a
significant amount (typically more than 20
% wt.) uniformly distributed at the base
solid dispersed phase.
Liniment - semisolid dosage
forms for local use, melting at
body temperature.
Ointments, creams, gels and pastes,
which are characterized by this sign, can
be attributed to liniment.
Excipients form a simple or complex base:
1. soft-media bases (petrolatum, lanolin etc.);
2. substances which increase the melting point
and viscosity of the base (paraffin, spermaceti,
hydrogenated vegetable oils);
3. hydrophobic solvents, water and hydrophilic
solvents;
4. emulsifiers (sodium laurel sulphate, twins,
cholesterol);
5. gelling agents (carbomer, alginic acid and its
salts etc.);
Excipients form a simple or complex base:
6. antimicrobial preservatives (benzalkonium
chloride, miramistin, cetrimide etc.);
7. antioxidants (α-tocopherol, ascorbic acid);
8. solubilizers (β-cyclodextrin);
9. perfume and deodorant agents (menthol,
essential oils);
10. pH regulators (citric acid, sodium phosphate
etc.).
Technological stages ointments
production
1. Sanitary preparing of facilities;
2. Preparing of the raw material:
a) melting of the base
b) filtering of the base
c) grinding and sieving of medicines,
3. The drugs introduction in the base
4. Ointments mass homogenization
5. Filtering ointments mass
6. Standardization of the finished product
7. Packaging, labelling.
Typical manufacturing process
breaks down into four individual
operations:
• Preparation of the oil phase. Flake/powder ingredients,
sometimes dry blended in advance, are dispersed into
mineral oil or silicone oil. Heating may be required to melt
some ingredients.
• Hydration of aqueous phase ingredients. Emulsifiers,
thickeners and stabilizers
are dispersed into water in a separate vessel. Heating may be
required to accelerate hydration.
• Forming the Emulsion. The two phases are blended under
vigorous agitation to form the emulsion.
• Dispersion of the Active Ingredient. The active ingredient
often makes up only a small proportion of the formulation;
this must be efficiently dispersed to maximize yield and
product effectiveness.
The Ointment Manufacturing Plants are ideal tools for the
production of Ointment, Cream, Lotions, Tooth Paste &
other emulsions & homogenizations.
Equipment for the ointments base
melting:
1. Tank with ointments
base
2. Funnel with filter and
heating elements
3. Heating elements
4. Pipeline for the ointment
unloading from tank and
transfer it in the reactor
Equipment for obtaining ointments mass:
Reactor-mixer
1. Body (corps)
2. Cover with hopper, viewing
window, valves, nozzles for
the various ointments
components introduction.
3. Anchor stirrer
4. Stirrer with blades
5. Turbine mixer
6. Shaft
Reactors of the Promvit
Universal Mixer "Yunitron“
1. Fixed tank
2. Removable mixing
nozzle
3. A bottom outlet
4. Shaft
5. Rotating scraper
6. Hole for connecting of
the homogenizer or
other equipment
7. Cover with hydraulically
management
CREAM VACUUM EMULSIFICATION
MIXER (Sainty Co)
TFZRJ vacuum emulsification
blender is specially
designed adopting
advanced technology of
Oversea according to the
cosmetic and ointment
production technology.
The machine is made up of
pretreatment boiler,
vacuum emulsification
blending boiler, vacuum
pump, hydraulic system,
pouring-out system,
electrocontrol system and
worktable.
Stage homogenization is necessary to
obtain homogeneous mass of ointment.
Equipment for homogenization:
1. Roller rubber of the ointment
2. Discs rubber of the ointment
3. Rotary-pulsation apparatus
Roller rubber the ointment
1. Parallel and horizontal
rotary shaft-rollers with
a smooth surface
2. Hopper
3. Scraper to remove the
ointment
Rollers rotate at different
speed - 38 rpm,
16 rpm
6.5 rpm
Discs rubber of the ointment
Consist from two disks.
One is fixed with a
hopper for loading
ointment mass.
Another disk rotates.
Ointment is rubbed
between the discs.
The degree of
homogenization
depends on the
distance between the
The diagram of the closed cycle with
rotary-pulsation apparatus
1. Tank for obtaining
ointment
2. Steam-jacket
3. Motor engine
4. Rotary-pulsation
apparatus
Problem at ointment
production
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When added to water, thickening, stabilizing and emulsifying
ingredients can form agglomerates which agitators 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.
Partially hydrated materials can build up on the vessel wall, intank baffles and parts of the agitator.
Agitators cannot 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.
Silverson mixer
The viscosity of some creams is such that
they cannot be manufactured by a
rotor/stator mixer alone. These can be
processed with a Silverson
Bottom Entry Mixer in conjunction with a
stirrer/scraper unit as illustrated.
Also suitable for products that increase in
viscosity or solidify on cooling.
The stirrer/scraper unit ensures that the
output of the Silverson mixer is
uniformly distributed throughout the
vessel and prevents a localized heat
build up on the walls of the jacketed
vessel.
Two-speed units available.Variable speed
can be obtained with an inverter.
Advantages of the Silverson
mixer
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Stable emulsion
Agglomerate-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
Production of Pharmaceutical
Creams & Ointments
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.
Requirements to the ointment base:
1. they should have release ability - structural and
mechanical properties are necessary for this
aim;
2. they should have ability well-hold drugs - have
absorb capacity;
3. they should are not changed under the
influence of environmental conditions and do
not react with drugs - possess chemical
resistance;
Requirements to the ointment base:
4. they should be pharmacological indifferent,
have not irritating and sensitizing effect;
5. they have be resistant to microbial
contamination;
6. they should have property for conform use
of the ointment.
Attributes of the ointments
quality:
1. Description
2. Identification of medicine
substances
3. Quantitative of MS
4. The particles size
5. pH
6. Microbiological purity
7. Quantity of acid and peroxide
8. Impurities
9. Sterility
10. Tightness of the container