LIQUID DOSAGE

FORMS
 OUTLINE
• Alcohols in water
• Volatile oils in water
• Water BP and USP (definitions and grade)
• Aromatic water
• Tincture extracts
• Syrups preparations and use
• Miscellaneous preparations(isotonic, non-aqueous, alcohols and
ethers, spirits and elixirs, tinctures and fluid extracts.
• Solubility and methods of increasing it
• Storage and packaging of liquid preparations
LIQUID DOSAGE FORMS

• In pharmaceutical terms, solutions are “liquid preparations that

contain one or more chemical substances dissolved in a suitable
solvent or mixture of mutually miscible solvents”
• Due to a particular pharmaceutical solution’s use, it may be
classified as oral, otic, ophthalmic, or topical.
LIQUID DOSAGE FORMS

• Still other solutions, because of their composition or use, may be

classified as other dosage forms.
• Tinctures may also be solutions of chemical substances dissolved
in alcohol or in a hydroalcoholic solvent.
• Alcohols in water are used as solvent, co-solvents or preservatives
in the pharma and cosmetic industry.
• For oral products, ethanol is the main alcohol use in compounding
• It can as well be used as disinfectant depending on the
concentration
• Aromatic Waters: Saturated solutions of volatile oils or other
aromatic or volatile substances in aqueous solvent.
• Spirits are alcoholic or hydro-alcoholic solutions of volatile
substances. Some spirits are used as flavouring agents, others are
medicinal.
 SYRUPS

• Saturated solution of sucrose in purified water, sweet viscous

preparations.
• Syrups containing medicinal substances are called medicated
syrups and those containing aromatic or flavored substances are
known as flavored syrups.
• Syrup BP’ is a solution of sucrose (66.7%) in purified water;

• Sugar-free’ syrups are obtained by replacing sucrose with

hydrogenated glucose, mannitol, sorbitol, xylitol, etc.
VOLATILE OILS IN WATER

• Also known as essential and sometimes medicinal oils, these are

used as stimulants, carminatives etc.
• They are also employed as flavouring agents.
• Most commonly however, they are used in perfumes, cosmetics.
ELIXIRS

• Sweet aromatic colored preparations. Main Ingredients of elixir

are ethyl alcohol, water, glycerin, propylene glycol, flavoring
agent, syrup and preservatives.
• Medicated elixir contains very potent drug such as antibiotics,
antihistamines, sedatives. Flavoring elixirs used as flavours and
vehicles.
WATER USP

Grades
• There are different grades of water used for pharmaceutical
purposes
• These waters can be divided into two general types: bulk waters,
which are produced on-site at the point of use
• and sterile waters, which are produced, packaged and sterilized to
preserve their anti-microbial quality throughout their packaged
shelf life
DEFINE THESE AND DESCRIBE HOW ONE
MAY DIFFER FROM ANOTHER PER USP AND
BP

• Purified water
• Water for injection
• Water for hemodialysis
• Sterile water for injection
• Sterile water for irrigation
MISCELLANEOUS

Isotonic Solutions: two solutions having the same osmotic pressure

and salt concentration as that of biological fluids
Nonaqueous solutions: this is a solution in which a solute is
dissolved in any solvent other than water.
Nonaqueous solvents include: benzene, alcohol, ether, toluene etc.
Tincture Extracts: concentrated herbal extracts obtained by soaking
the barks, leaves, roots etc. of one or more plants in alcohol or
vinegar
FLUID EXTRACTS

• An alcoholic or hydroalcoholic liquid containing selected active

components of herbal material obtained by percolation or
maceration in alcohol or a hydroalcoholic mixture.
• Read on the differences between maceration and percolation fluid
extraction
 INFUSIONS AND DECOCTIONS

• An infusion is made by pouring water over plant material then

allowing it to steep. The water is usually boiling,
• but cold infusions are also an option, and for certain herbs can be
more beneficial
• A decoction is made by boiling plant material, usually the bark,
rhizomes, roots or other woody parts, in water.
• General guidelines are to boil your root or bark for at least 30-45
minutes
• Maceration. it involves the steeping of raw material in a solvent,
which is later strained out. It is widely used for the preparation of
tinctures, but is very inefficient for the collection of solutes.
MACERATION: ORGANIZED

• Selected Plant material

• Placed in a closed vessel
• All of the appropriate menstruum added
• Allowed to stand for a week with occasional shaking.
• Liquid strained off
• Solid residue pressed to recover virtually all occluded solution
• Mix strained with pressed
• Filter to remove insoluble components and stored.
• Filtrate is not adjusted for volume
DOUBLE AND TRIPLE
MACERATION
• In triple maceration The drug is macerated thrice having each
maceration of one hour duration.
• In double maceration strain the liquid after each maceration and
press the marc.
• In triple maceration strain the liquid after each maceration and
press the marc after the last maceration.
MACERATION FOR
UNORGANIZED DRUG?
• Differentiate between organized and unorganized drug in
both definition and process
PERCOLATION

• involves the subjection of raw material to continuous flow of

fresh solvent. This produces stronger extracts, but at increased
solvent cost.
• Repeated percolation using a number of extractors with solution
percolates (solvent already containing extracted components),
partially decreases the problem.
• After medicinal material powder is placed in a percolation tank,
the extraction solvent is continuously added, and percolation
extract is collected simultaneously.
PERCOLATION: STEPS

• Size reduction
• Imbibition
• Packing
• Maceration
• Percolation
• Pressing the marc
PERCOLATION
DIGESTION

• This process is a modified form of maceration where the drug is

extracted by heating at a particular pressure.
• This will increase the penetration power of the menstruum, so that
there is complete extraction of the drug.
STORAGE AND PACKAGING OF
LIQUID PHARMACEUTICALS
• The pharmaceutical pack is as important as the medicine
packaged.
• The closure, such as a stopper, lid, top or cap, is an integral part of
the pack.
• The primary pack is in direct contact with the medicine
• It must be compatible with the medicine, and must not change it in
any way
• Packaging is the means of economically providing containment,
protection, presentation, identification, information, convenience
and compliance, for a product during storage, distribution, display
and use.
• The role of packaging seems to be constantly expanding, for
example, in anti-counterfeiting, branding and providing
distinguishing features to the drug product to avoid errors as well
as in the monitoring of patient.
 PRIMARY PACKS

• The wide range of pharmaceutical products, especially liquids

(such as solutions, suspensions, emulsions), some of which are
sterile, obviously require a great diversity, both in primary pack
design and in packaging materials.
• The latter include paper, glass, plastics, rubber, metal or
combination materials such as laminates. Examples of primary
packs include blister packs, strip packs, sachets, bottles, ampoules,
vials, bags, tubes and syringes.
• The primary pack may contain many doses (i.e. be a multiple-unit
pack, e.g. a bottle containing many tablets) or a single dose (i.e. be
a single-unit pack, e.g. blister pack, sachet).
• The primary pack must offer child-resistance to restrict children’s
access to the product.
• Child resistant packs have been successful in reducing accidental
poisoning of children.
• At the same time, the pack must allow access to the user, who may
be elderly or frail and may have difficulty opening packs.
• Difficult-to-open packs are not always fully reclosed between
administration events – and this may compromise the product.
• In addition, the primary pack must be tamper-resistant and tamper-evident to improve
the product’s security from pilferage and deliberate contamination and safeguard the
product’s legitimate user
• In addition, the primary pack must protect the product against
atmospheric factors, such as extremes of temperature, light,
moisture, oxygen, carbon dioxide, particulates (e.g. dust, dirt),
• as well as biological hazards, such as microorganisms, insects and
rodents, and enable product stability.
• .
• Light can provide the energy necessary for a drug isomer to
change its configuration. Protection from light is usually achieved
by using an opaque or amber-coloured container.
• Oxygen can cause drug degradation via oxidation.
• Carbon dioxide can dissolve in the water in unbuffered aqueous
products, and lower their pH by forming carbonic acid.
• Water can cause drug degradation via hydrolysis.
• Moisture gain into a product can also cause dilution of liquid
products,
SECONDARY PACKAGE

• Secondary packs also contribute to protection against atmospheric

actors to some extent.
• Although their major role is to provide protection against
mechanical hazards, such as shock (e.g. when dropped),
compression, vibration, abrasion, puncture, etc., during handling,
storage and transport.
GLASS

• Glass is produced by heating together various inorganic substances

to form a molten mass, and then rapidly cooling the latter which
solidifies in a non-crystalline state.
• Although glass is fairly inert, it is not totally so.
• Basic colourless glass used for most packaging applications
contains
• silica at 59–75%,
• calcium oxide at 5–12%,
• sodium oxide at 12–17%,
• alumina at 0.5–3% and possibly trace compounds
• Some of the glass components can leach out of the glass and into
the contents.
• For example, sodium which is loosely combined with silicon can
leach out from the glass surface into water contained within the
glass, thus increasing the alkalinity of the contents.
• Another problem occurs when glass is stored at high temperature
and high humidity or when ambient temperature and humidity
conditions fluctuate greatly
• Salts in the glass migrate from the body of the glass and
accumulate at its surface. This physical change is called blooming.
• To reduce leaching, the glass can be soaked in heated water or a
dilute acid solution, which removes most o the sur ace-leachable
salts.
• The glass surface can also be treated, for example, with a sulphur
compound, to make it more resistant to water or acidic solutions.
PHARMACEUTICAL TYPES OF
GLASS
• Thus, different types of glass exist and the least reactive are used
to package pharmaceuticals
• Four types of glass – defined precisely in the United States
Pharmacopoeia (USP) as types I, II, III and NP glass – are used.
 TYPE 1

This is the best pharmaceutical grade and is produced by adding boron

oxide to glass, hence this glass is also called borosilicate glass.
It is the most inert glass, shows the least amount of leaching of glass
components, and is used in ampoules and vials or liquid parenteral
products.
Due to its lowest coefficient of thermal expansion, this glass is highly
resistant to temperature changes,
e.g. during severe sterilization procedures. Type I glass is used to
package slightly acidic solutions.
This glass is also the most expensive to produce
 TYPE 11
• This is the next grade and is made from the same materials as
standard glass (soda lime glass) but its surface is treated with
sulphur dioxide.
• The latter reacts with the oxides found on the glass surface, or
example, sodium oxide is converted to sodium sulphate, which can
then be removed by washing the glass.
• Such surface treatment, thus, reduces the amount of ions that can
leach out o the glass. Hence, type II glass is also referred to as
treated soda lime glass or dealkalized soda lime glass.
• Type II glass is suitable for solutions that can be buffered to
remain below pH 7.
• At higher pH, the oxides in the glass are more easily leached out.
TYPE 111

• This is the next (lower) grade and is standard soda lime glass and
is analogous with glass used in food packaging.
• It is used to package large volumes (normally >100 mL). The large
volume to surface area of product in contact with the glass surface
limits the amount of glass components that can leach into the
product.
NP GLASS

• This is the lowest grade and is called non-parenteral glass, and, as

the name suggests, is not used for packaging parenteral products.
• As small volumes of the latter would be easily contaminated by
sodium and other materials leaching out of the glass.
• NP glass is however suitable for packaging large volumes
(normally >100 mL) of topical products like creams and of oral
products, such as mouthwashes.
 PLASTICS

• The versatility of plastics has led to their use in almost all parts of
our lives, and they are used to package a wide variety of domestic
products.
• They are widely used as containers (e.g. bottles, trays), closures
(e.g. screw-tops), cling films, carrier bags, sacks, overwraps, etc.
•

• Plastics are also widely used to package medicines in a

variety of containers, such as
• Bottles for solid and liquid products
• Tubes for creams, ointments and gels
• Pouches to contain individual suppositories
• Blister packs
• Bags to contain intravenous solutions and parenteral
nutritional products
• Bottle closure
• There are many different types of polymers, or polymer mixes,
used as packaging plastics.
• In addition, the different plastics are available in many different
grades.
• Commonly used packaging plastics include: polyethylene,
polystyrene, polypropylene, polyethylene terephthalate, polyvinyl
chloride, polyvinylidene chloride, polyamides (nylons),
polycarbonates.
• Their use as a pharmaceutical packaging material is growing due
to the significant advantages and consumer preference for plastic.
• Plastics are light, shatterproof and can be clear or opaque (clarity
may be desired for product inspection; opacity to protect the
contained medicine).
• Plastics are easily shaped and sealed, which gives great versatility
in the design of the pack, and allows the inclusion of
administration aids, such as a squeezable dropper.
• Plastics do however suffer from certain disadvantages compared to
traditional packaging materials, such as glass and metal, which
limit their use.
• No plastic can yet match the chemical inertness and
impermeability (to environmental gases, such as oxygen) of type I
glass.
• Plastics are less resistant to heat and long-term light exposure than
glass and metal. Plastics are also liable to undergo stress cracking,
where the presence of solvents, such as alcohols, acids or oils,
cause a plastic pack to become brittle, crack and eventually fail
over time.
• Certain components of the plastic packaging material can also
leach out of the plastic and into the product.
• Plastics can be divided into two classes:
• thermoplastics and
• thermosetting plastics.
• In general, thermoplastics have linear and branched polymer
chains, while thermoset polymers are cross-linked.
• At high temperature, thermoplastic polymers melt and become
liquid, the polymer chains flow and the material can be moulded
into a variety of shapes, such as bottles, tubes and films.
• Softening and re-shaping by the application of heat and
mechanical force can be performed multiple times.
• Examples of thermoplastics include: polyvinyl chloride,
polyethylene, polystyrene, polypropylene, nylon, polyester,
polycarbonate.
DIFFERENT TYPES OF PLASTICS
USED IN THE PHARMA INDUSTRY
SOLUBILITY

• Solubility is a property of a substance, determining the degree at

which it can dissolve.
• A solute is dissolved into a solvent to form a homogenous solution
where molecules are uniformly distributed.
• The rate at which this occurs depends on chemical and physical
parameters such as the solvent used, the polarity and particle size
of the solute, the presence of other ions in the solvent, as well as
temperature and pressure.
• Read on how the physico-chemical factors mentioned above
enhances the solubility of a pharmaceutical material
EXTRACTION OF OIL

• Read on the difference between - Screw and hydraulic press

methods of oil expression and extraction
THANK YOU