Chapter Four
Production of liquid, cream, ointment
Aristopharma Ltd.
Quality – The Unit We
Chapter Four: Production of liquid, cream, ointment
Liquid
Liquid preparations for oral use are usually solutions, emulsions or suspensions
containing one or more active ingredients in a suitable vehicle; they may in some cases
consist simply of a liquid active ingredient used as such. Liquid preparations for oral
use are either supplied in the finished form or, with the exception of Oral emulsions,
may also be prepared just before issue for use by dissolving or dispersing granules or
powder in the vehicle stated on the label.
The vehicle for any liquid preparation for oral use is chosen having regard to the
nature of the active ingredient(s) and to provide organoleptic characteristics
appropriate to the intended use of the preparation. Liquid preparations for oral use
may contain suitable antimicrobial preservatives, antioxidants and other excipients
such as dispersing, suspending, thickening, emulsifying, buffering, wetting,
solubilizing, stabilizing, flavouring and sweetening agents and authorized colouring
matter. Liquid preparations for oral use may be supplied as multi dose or as single-
dose preparations.
Advantages of Liquid Dosage Forms:
1. They are homogenous; there the medicament is uniformly distributed
throughout the liquid.
2. The doses can be easily adjusted according to the need of the patient.
3. They can be easily measured with the household measured.
4. They are more quickly effective than tablets or capsule because they are
already in the solution form and absorption starts quickly.
5. They can be easily colored, flavored or sweetened.
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Chapter Four: Production of liquid, cream, ointment
6. Children or patient who cannot swallow tablets or capsule can easily ingest
solutions.
Disadvantages of Liquid Dosage Forms:
1. They are difficult to carry and there are chances of breakage of
container with the complete loss of contents.
2. In some medicaments their unpleasant taste and flavor is difficult to mask.
3. They are less stable as compared to solid dosage form because deterioration
is faster in solutions.
There are two types liquid in ARISTROPHARMA LTD.
1. Oral liquid
2. Topical liquid.
Oral liquid preparations include-
Oral Syrup: Oral syrup is a concentrated solution of a sugar, such as sucrose, in
water or other aqueous liquid, sometimes with a medicinal agent added;
usually used as a flavored vehicle for drugs. It is commonly expanded to
include any liquid dosage form (e.g., oral suspension) in a sweet and viscid
vehicle.
Suspension: A suspension is a two phased system in which a finely divided
solid is homogenously dispersed in a continuous phase of solid, liquid, or gas
by use of a proper suspending agent. The undisclosed solid exists in
equilibrium with a saturated solution of the solid in the continuous phase. A
pharmaceutical suspension is a coarse dispersion in which insoluble solid
particles are suspended in a liquid medium.
General Manufacturing Process of Oral Liquids:
The general manufacturing of oral liquids in the liquid section of ARISTOPHARMA Ltd.
is briefly described below with a flowchart:
Weighing of active ingredients and excipients
Mixing of excipients with certain amount of purified water as specified in the
Batch Production Record (BPR) by the aid of a mechanical stirrer
Addition of active ingredient/s and mixing
Volume adjusted and Passing through a pump to the storage vessel
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Chapter Four: Production of liquid, cream, ointment
Transfer of the solution to the filling vessel through 50 micron Cartridge filter.
Filling, Flushing of Nitrogen (N2) & Sealing of Bottles (glass or pet) containing oral
liquids
Condition for manufacturing of Oral Liquids:
• Relative Humidity: Not more than 55%.
• Temperature: Below 30 ͦC
In the packaging unit, filled & sealed bottles are sequentially
→ Labeled
→ Packed with an insert in the intermediate
carton → Final packed in master carton.
Machines used in the Oral Liquid Manufacturing unit:
Name of the Machine Function Capacity
Jacketed Manufacturing Vessel
Mixing 1000 Liter
Origin: China
Charge Vessel Manufacturing 2000 Liter
S.S Storage VAT Storage 2000 Liter
Cartridge Filter Filtration -
Filling & Sealing of
Bottle Filling & Sealing Machine 2300 bottles/hr
Oral Liquid
Homogenizer Mixing and Milling 1200 Liter
5000-8000
Bottle dryer Drying bottle
bottles/hr
Mixing tank Origin: China Mixing 1000L
Double head manually filling
Filling 38-44/min
machine Origin: India
Mono block rotary volumetric filling
machine. Origin:India Filling 6000/hour
-
Cartridge filter dry
Drying
Suspension Preparation:
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Chapter Four: Production of liquid, cream, ointment
Suspension is a liquid dosage form in which solid particles are dispersed in a
liquid phase. A suspension of a finely divided powder will maximize the potential for
rapid dissolution. Addition of a surface active agent will improve dispersion of a
suspension and may improve the absorption of very fine particle size suspensions
otherwise caking may be a problem. Smaller particles have higher solubility and will
tend is disappear with the drug coming out of solution on larger particles.
Steps involved in Suspension Preparation:
Dispersion of suspending agent
Transfer to manufacturing vessel containing sucrose solution
Addition of active ingredients and excipients
Mixing with continuous stirring
Adjustment of final volume with purified water
Filling & sealing
Packaging
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Chapter Four: Production of liquid, cream, ointment
Cream and Ointment
Cream and ointments are dosage forms for local application. Here, generally O/W
creams are prepared. Ointment is an O/O preparation. Due to the presence of water
soluble base in oil in water type creams they can be easily removed from the skin. The
aqueous creams have a tendency to bacterial and mold growth; therefore a
preservative must be added. Even if a preservative has been incorporated care must
be taken for complete cleanliness of the apparatus used in the manufacture of creams
and containers used for packing the creams. They are divided into two types: oil-in-
water (O/W) creams which are composed of small droplets of oil dispersed in a
continuous aqueous phase, and water-in-oil (W/O) creams which are composed of
small droplets of water dispersed in a continuous oily phase.
Ointments:
Topical ointment administration is employed to deliver a drug at or immediately
beneath the point of application. Although occasionally enough drugs is absorbed in
the systemic circulation to cause systemic effects. A large no. of topical medicaments
is applied to skin, although topical drugs are also applied to eye, nose, throat, ear etc.
General process of manufacturing Cream
Water phase + Oil phase
Water phase to oil phase in a steam jacketed vessel
Blending by mechanical stirrer
Filling & Sealing
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Chapter Four: Production of liquid, cream, ointment
Ambushing
Release
Manufacturing Process of Ointments:
Oil Phase-I + Oil Phase-II
Oil phase-I to Oil phase-II in a Steam Jacketed Vessel
Addition of active ingredients
Blending by Mechanical stirrer
Filling
Sealing
Ambushing and released
Equipment Used for Manufacturing Topical Preparation:
Machine Name Specification and Origin Capacity
Double head tube filling
Precitech industries, India
machine
Charging vessel Myth industries, Bangladesh 100L
Chaina wenzhou T-zone
Vacuum mixing emulsifier 90 kg/L
machinery manufacturing co. ltd
Homogenizer India -
Transfer pump U.S.A -
Automatic labeling machine Korea 6000/hr
Automatic tube filling, Sealing 35-40
India (Technology Japan)
machine tube/min
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Chapter Four: Production of liquid, cream, ointment
Semi-Automatic Tube filling, 32-35
India
Sealing machine tube/min
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