Manufacture of liquid
(PART-IV)
16.05.2020
INTRODUCTION
• Liquid dosage forms are designed to provide the maximum
therapeutic response in a target population with difficulty swallowing
tablets and capsules and/or to produce rapid therapeutic effects.
• The major ingredient in most liquid dosage forms is water.
• While it is the safest and most palatable solvent option, water quality
is significant for the stability of pharmaceutical dosage forms.
Definition
• Liquid dosage forms are essential pharmaceutical products which
involves a mixture of active drug components and
nondrug components (excipients).
• Liquid dosage forms are prepared:
a. by dissolving the active drug substance in an aqueous or non- aqueous
(e.g. glycerin, ether, alcohol) solvent
b. By suspending the drug in appropriate medium or
c. By incorporating the drug substance into an oil or water phase.
• Ex: Suspension, Emulsion, Syrups, Elixers.
Steps of Liquids Manufacturing
Process
• Planning of Material Requirements
• Liquid Preparation
• Filling and Packing
• Sales of Drug Products
• Vendor Handling
• Customer Service
Planning of Material Requirements
• Research and development of protocols and selection of materials;
acquisition and analysis of raw materials; physical plant design,
building, and installation; equipment selection and acquisition;
personnel selection and initial training; and monitoring information
system.
Liquid Preparation
• Research and development of protocols concerning liquid
compounding; scale - up of the bulk product compounding; physical
plant control and maintenance; equipment maintenance and
renovation; continuous training of personnel and personnel
compensation plan; and supervision of system reports.
Filling and Packing
• search and development of protocols concerning filling and packing;
scale - up of the finished drug product filling and packing; physical
plant control and maintenance; equipment maintenance and
renovation; continuous training of personnel and personnel
compensation plan; and supervision of system reports.
Sales of Drug Products
• Research and development of protocols concerning product storage;
distribution process; continuous training of personnel and personnel
compensation plan; and supervision of system reports.
Vendor Handling
• Research and development protocols concerning precautions to
maintain product stability; control of vendor stock; and sales system
reports.
Customer Service
• Research and development of protocols concerning home storage and
handling to maintain product stability; relations with health insurance
companies and health care professionals; educational materials for
patient counseling; and customer service system reports.
Raw materials Weighing &
Measuring
Mixing Distilled
water
Filling
Packing Finished
Product
Pilot Plant Scale-Up storage
Techniques for
Quality
liquid orals
Assurance
Stages of operations: 1. Tank selection
•Material of the tank must not be
additive to the product
•The shape and size of
equipment must be selected
according to the batch size
•The tanks are usually constructed
of polished stainless steel of
different grades
•Teflon and glass lined tank.
•Adequate clean-up procedures
developed.
DIFFERENT TYPE OF MIXERS
•Simple mixing is essential to
increase flow of liquids.
•If the liquid is of high viscosity,
high electrical stirrer may be
used.
•Addition of ingredients in
proper order have vital
important.
•At high viscosity the chance of
air entrapment.
AIR ENTRAPMENT MINIMIZE
• VERSATOR • By reducing agitator speed
• By caring out the mixing
procedure in enclosed tank
under vacuum
• The alternative procedure to the
all is versator
3.DISPERSION
•Suspensions and emulsions
require considerably greater
shear forces
•Laboratory formulation is
difficult to duplicate at large
scale
•Dispersion produced by
colloidal mill or an immersion
homogenizer.
•Variety of equipment should
evaluated for better results.
4. FILTRATION AND
CLARIFICATION
•Filtration procedure, requires careful evaluation to ensure that
pilot scale-ups will exhibit the same degree of clarity as their
laboratory counterparts.
•During the pilot run the clarity of the filtrate should be checked
periodically, in order to establish schedule for changing pads,
cake, or cartridges, depending on the type of filtration
employed.
•In filtration, filter pads are used which is made up of asbestos
and cellulose.
Selection of filtration depends on
•The product viscosity Volumes
•Volume
• Rate requirement
5. TRANSFER AND FILLING
• Filling – important parameter in the transfer of liquids from tank to
tank and into containers.
• New batches should not be started until the previous batches are
completely filled and the tanks are emptied.
• Bins and Piping
Methods for filling of liquids
•The selection of equipment depends on characteristic of liquid such as,
viscosity, type of packaging, surface tension.
•Gravimetric (specific weight)
•Volumetric (specific volume)
•Constant volume filling
Excipients Used In the Formulation
of Liquid Dosage Forms
1. Vehicles/ Solvents
• Aqueous (e.g., water, polyhydric alcohols, hydro-alcoholic solutions
and buffers)
• Oily (e.g., vegetable or mineral oils, organic oily bases, emulsified
bases etc).
• a. Water as a solvent
• Water is the most widely used solvent in pharmaceutical formulations. In
routine use, it lacks toxicity, is compatible with bodily fluids, and can dissolve
most compounds that are used as pharmacologic agents (due to its high
dielectric constant) but likely to cause instability of hydrolytically unstable
drugs and provides suitable media for microbial growth.
b. Alcohol as a solvent
• Alcohol frequently referred to as ethyl alcohol or ethanol is the most commonly
used solvent in liquid pharmaceutical formulation next to water.
• It is a clear, colourless, mobile, and volatile liquid with a slight, characteristic
odour and burning taste.
• Alcohol USP contains ethanol, C2H5OH, not less than 92.3% and not more than
93.8%, by weight, which corresponds to not less than 94.9% and not more than
96.0%, by volume.
• Ethanol is miscible with water, glycerine, propylene glycol, and polyethylene
glycol 400.
• It is used as a primary solvent for many organic compounds. Water–alcohol
mixtures can be very effective in solubilizing poorly soluble drugs
c. Glycerin, USP (Glycerol) as a solvent
• Glycerin is miscible with water, alcohol, propylene glycol, and
polyethylene glycol 400.
• As a solvent, the solubilizing properties of glycerin are comparable to
alcohol but because of its viscosity, solutes are slowly soluble in it
unless it is rendered less viscous by heating.
• Also, the increased viscosity imparted to the final product may be an
undesired outcome of the use of this solvent.
a. Water as a solvent
