PDDS 211: Liquid Dosage Form ▪ Can be used by any route of

administration
SOLUTIONS ▪ Easy to adjust dose
• Liquid preparations that contain one or more Solutions by Preparation
chemical substances dissolved in a suitable
solvent or mixture of mutually miscible • Extracts or parenterals
solvents o Composition:
▪ Solute – smallest amount
Classification ▪ Solvent – Larger amounts, can dissolve
the solute, nontoxic, safe for ingestion
• According to route or site of application
or topical application, aesthetically
▪ otic, oral, ophthalmic, topical
acceptable
• According to solvent used
▪ Additive – colorants, flavorants,
▪ Aqueous and non-queous
preservatives or buffering agents,
Otic, Oral, Ophthalmic, Topical antioxidants

• Otic Solutions General Rules in Preparing Solutions

o intended for instillation in the outer ear, are
1. Know the solubility characteristics of the
aqueous, or they are solutions prepared with
drug or chemical
glycerin or other solvents and dispersing
2. Choose the proper solvent
agents
3. The salt form of the drug is used
o Example:
4. When adding salt to syrup, dissolve salt in a
▪ Antipyrine and Benzocaine Otic
few mL of water then add syrup to volume
Solution and Noemycin and Polymyxin
5. If an alcoholic solution of a purely water-
B Sulfates and Hydrocortisone Otic
soluble drug is used, add the aqueous
Solutions.
solution to the alcoholic solution
• Oral Solutions
o are liquid preparations, intended for oral Solubility
administration, that contain one or more
substances with or without flavoring, • The expression of the quantity of a drug that can
sweetening, or coloring agents dissolved in be maintained in solution in a given solvent at a
water or cosolventwater mixtures. given temperature and pressure.
o may be formulated for direct oral • It is usually expressed as the number of
administration to the patient or they may be milliliters of solvent required to dissolve 1 gram
dispersed in a more concentrated form that of the drug.
must be diluted prior to administration. • Stated in terms of the parts of solvent needed to
• Ophthalmic Solution dissolve one part of the solute (US):
o sterile preparation to be used on the eyes.
• Topical Solutions
o are solutions, usually aqueous but often
containing other solvents such as alcohol
and polyols, intended for topical application
to the skin, or as in the case of Lidocaine
Oral Topical Solution, to the oral mucosal
surface
o The term “lotion” is applied to solutions or Types of Solution
suspensions applied topically.
• Unsaturated solution
ADVANTAGES: o a solution that contains less amount of solute
that the solvent can dissolve.
1. Completely homogenous doses
• Saturated solution
2. Immediate availability for absorption and
o s one that contains the maximum amount of
distribution
solute that the solvent will accommodate at
3. Provides a flexible dosage form
room temperature and pressure.
▪ Easy to swallow
• Supersaturated solution o Preparation of Purified Water
o one that contains a larger amount of solute ▪ Distillation
than the solvent can normally accommodate • Stills in various capacity
at that temperature and pressure • 10 – 20% of the first portion of last
portion (10% of total volume)
Factors Affecting Solubility
distillate is discarded
1. Temperature ▪ Ion- exchange
2. 2Pressure • resin with cations and anions
3. pH of the solution phenolic, carboxylic, amino and
4. 4Particle size sulfonated resins
5. Physical agitation • Deionized or demineralized water.
6. Nature of the solute ▪ Reverse osmosis
• “Cross flow” membrane filtration
Polar & Nonpolar Solvents • Equipped with membrane filters
• A liquid composed of polar molecules is a polar  Microfiltration – (0.1 -2 um)
solvent. Water and ethanol are polar solvents.  Ultrafitration – (0.01 – 0.1 um)
• A liquid composed of nonpolar molecules is a  Nanofiltration – (0.001 – 0.01
nonpolar solvent. Hexane is a nonpolar solvent. um)
 90 to 99% of ions
General Rules of Solubility  Filtered portions are called
PERMEATE
• “like dissolves like”
2. Alcohol - C2H5OH
• Organic compounds with polar groups may
▪ 94.9 – 96% ethanol by volume
dissolve in polar solvents
▪ 99.5% is dehydrated alcohol
• Organic compounds increasing in molecular
▪ Miscible with water, with preserving
weights reduces its solubility in polar solvents
action
• Branched chains are more soluble than straight ▪ Alcohol content limitsin OTC oral prep:
chain compounds
• Under 6 y/o – 0.5%
• Similarity in structure increases solubility
• 6 to 12 y/o – 5%
Soluble • Over 12 and adults – 10%
3. Diluted alcohol
• Salts of inorganic compounds ▪ Mixture of equal volumes alcohol and
• Salts of monovalent cations water
• Salts of alkali metals ▪ Final volume of the mixture is NOT the
• Ammonium and quaternary ammonium salts sum of the individual volumes of the 2
• Nitrates, acetates, chlorates and lactates components bcoz liquids contact upon
• Sulfates, sulfites and thiosulfates mixing and the final volume is
• Chlorides, bromides, iodides generally about 3% less than what
would otherwise be expected
Insoluble • 50%+50% = 100%  97% (due to
contraction)
• Salts of multivalent cations and anions
4. Rubbing alcohol
• Hydroxides and oxides
▪ 70% of ethanol, additives
• Phosphates, carbonates, silicates, borates, and ▪ Nlt 355 mg per 100 ml content of
hypochlorites sucrose octa-acetate or 1.4 mg of
Solvents denatonium benzoate
▪ Volatile and flammable
1. Purified water ▪ Rubefacient, germicide, antiseptic,
▪ Clear, colorless, odorless and neutral vehicle for topical preparation
(pH 5 – 7) 5. Isopropyl rubbing alcohol
▪ Contain less than 0.1% of total solids ▪ 70% isopropyl, 91% - External
▪ Prepared by distillation, ion exchange application, for diabetic patients
method and reverse osmosis ▪ External application as rubefacient and
soothing rub and as a vehicle for topical
products
 ▪ 91% is used for diabetic patients in o Methods: Maceration, percolation, digestion,
preparing needles and syringes for decoction, infusion
hypodermic injections of insulin and for • Maceration
disinfecting the skin o is the process in which the solid ingredients
6. Glycerin (Glycerol) are placed in a stoppered container with the
▪ CH2OH•CHOH•CH2OH whole of the solvent and allowed to stand
▪ Clear, syrupy liquid, sweet taste for a period of at least three days, with
▪ Miscible with water and alcohol frequent agitation. The mixture is strained
▪ Viscous, preservative action and the marc pressed, and the combined
7. Propylene glycol liquids are clarified by filtration or by
▪ CH3CH(OH)CH2OH decantation after standing.
▪ Viscous liquid, miscible with water and • Percolation
alcohol o where the active ingredients are extracted
▪ As substitute for glycerin from a macerated drug mass in a narrow
cone-shaped vessel open at both ends
Other Non-polar Solvents
(percolator) through the passage of an
• Hydrocarbons or glyceryl esters. Peanut, sesame, extracting liquid called menstruum
corn, cottonseed, and mineral oil are most • Digestion
frequently chosen as solvents or vehicles. o This is a form of maceration in which gentle
heat is used during the process of extraction.
• Infusion
o is a dilute solution of the readily soluble
constituents of crude drugs for a short period
of time which either cold or boiling water is
added
• Decoction
o extracts water-soluble and heat stable
constituents from crude drugs by boiling in
water for 15 minutes, cooling, straining and
passing sufficient cold water through the
drug to produce the required volume

Complex Solution

• this is a combination of at least two of the above

Methods of Preparation procedures with or without controlled
application of heat.
• Simple solution
o done by dissolving the solute in a suitable SYRUPS
solvent, which may contain other
• Concentrated aqueous preparations of sugar or
ingredients, which stabilize the active
sugar substitute with or without added flavoring
ingredients.
agents and medicinal substances.
• Solution by chemical reaction
• Syrups containing flavoring agents but not
o is prepared by reacting two or more solutes
medicinal substances are called non-medicated
with each other in a suitable solvent.
or flavored vehicles (Cherry Syrup)
o Example: Magnesium Citrate Oral solution
• Medicinal syrups are those to which therapeutic
• Solution by distillation
compounds have been added (Guaifenesin
o consists of distilling the volatile principles
Syrup)
from a drug inside a copper wire cage,
• When purified water alone is used in making the
which allows the free passage of vapors and
solution of sucrose, the preparation is known as
boiling water
syrup or simple syrup.
• Solution by extraction
• In addition to sucrose certain other polyols such
o Drugs or pharmaceutical necessities
as glycerin or sorbitol may be added to retard
vegetable or animal origin are often
crystallization of sucrose or to increase the
extracted with water or with water
solubility of the added ingredients, and also to
containing other substances.
prevent cap-locking
ADVANTAGE: Syrup

• Provides a pleasant means of administering a • Concentrated or nearly saturated solution of

liquid form of disagreeable tasting drug. sucrose in water.
• They may particularly effective in the • A simple syrup contains only sucrose and
administration of drugs to youngster, since their purified water (e.g. Syrup, NF).
pleasant taste usually dissipates any reluctance • Has concentration of 85% - self-preserving
on the part of the child to take the medicine • A solution of a polyol, such as sorbitol, or a
• The fact that syrups contain little or no alcohol mixture of polyols, such as sorbitol and glycerin,
adds to their favor among parents is commonly used.
• Sorbitol Solution, USP, which contains 64% by
Components of Syrups
weight of the polyhydric alcohol sorbitol
• The sugar, sucrose, or sugar-substitutes used to
SELF-PRESERVING EFFECT
provide sweetness and viscosity
• Flavorants, Colorants • Syrup has a specific gravity of about 1.313
• Antimicrobial preservatives o each 100 mL of syrup weighs 131.3 g.
o Benzoic Acid (0.1-0.2%) • Sucrose present is 85 grams, the difference
o Sodium Benzoate (0.1-0.2%) – for acidic between 85 and 131.3 g, or 46.3g represents the
preparation weight of the purified water.
o Methylparaben, propyl and butylparaben • Thus, 46.3 g, or mL, of purified water is used to
(0.1%) dissolve 85 g of sucrose.
o Alcohol (15-20%) *<12% = preservative • The solubility of sucrose in water is 1 g in 0.5
effect mL of water; therefore, to dissolve 85 g of
• Others: contain special solvents, solubilizing sucrose, about 42.5 mL of water
agents, thickeners, or stabilizers
Methods of Preparation
Sucrose and Non-sucrose-based syrups
• Solution with heat
• Sucrose o Hydrolysis results to invert sugar
o glucose, fructose o Excessive heat results to caramelization
o non-sugar polyols (sorbitol, glycerin, • Agitation without heat
propylene glycol), • Addition of sucrose to a prepared medicated
▪ polyols, though less sweet than sucrose, liquid or a flavored liquid
have the advantage of providing o Extract or fluidextract
favorable viscosity, reducing • Percolation
caplocking (which occurs when sucrose
crystallizes) NON –AQUEOUS SOLUTIONS
• Non-sucrose Syrups
Elixirs
o In some cases acting as cosolvents and
preservatives. • defined by the USP as "clear, sweetened,
o A 70% sorbitol solution is commercially hydroalcoholic liquids intended for oral use.
available for use as a vehicle • Advantages
o non-nutritive sucrose-substitute such o compared to syrups, elixirs are usually less
methylcellulose and HEC, synthetic sweet and less viscous because they contain
aspartame, saccharin. a lower proportion of sugar
▪ when a reduction in calories or • Other solvents: glycerin and propylene glycol
glucogenic properties is desired, as with • Alcohol content ranges from 5-40% (10-80
the diabetic patient. proof), conc of 10-12% is self-preserving.
▪ non-nutritive sweeteners do not impart
• Medicated or non-medicated
the characteristic viscosity of syrups
• By simple solution with agitation
and require the addition of viscosity
• Commonly used elixirs:
adjusters, such as methylcellulose.
o Aromatic elixir, Compound Benzaldehyde
elixir, Iso-alcoholic elixir
• The hydroalcoholic character elixirs are better Spirits
able than aqueous syrup to maintain both water
soluble and alcohol soluble components in the • Also known as essences
solution. • are alcoholic or hydroalcoholic solutions of
• Also because of their stable characteristic and the volatile substances (usually volatile oils) with
ease of which they are prepared (by simple alcohol contents ranging from 62-85% (124-170
solution), from a manufacturing stand point, proof).
elixirs are preferred over syrups • They are most frequently used as flavoring
agents
Tinctures • Also used for their medicinal effect
• most spirits are a convenient means of obtaining
• are alcoholic or hydroalcoholic solutions
a proper amount of a flavoring oil.
prepared from vegetable or chemical substances.
• Whisky and Brandy are prepared by distillation.
• The concentration of alcohol ranges from 15 –
o distilled alcoholic beverage made from
80%
fermented grain mash
• The concn of solute varies up to 50%
o produced by distilling wine
• Tinctures may be alcoholic solutions of
• Compound Orange Spirit (orange, lemon,
nonvolatile substances which are generally
coriander and anise oils), Camphor Spirit, and
extracted by maceration or percolation.
Compound Cardamon Spirit are prepared by
• Tinctures of chemical substances are prepared by simple solution.
simple solution
• Peppermint Spirit, USP is prepared by solution
• Percolation is the procedure of choice when the with maceration
crude drugs are cellular in structure; plant
• Advantages
exudates tend to become impacted in the
o Spirits can contain a greater concentration of
percolator and stop the flow so that maceration is
alcohol than the corresponding aromatic
preferred in such preparations.
waters.
• Tinctures of potent drugs represent the activity of
10 g of the drug in each 100 ml of the tincture; Liniments
they are 10% tinctures.
• With a few exceptions, nonpotent tinctures • Liniments are alcoholic or oleaginous solutions
represent 20 g of the drug per 100 ml of tincture or emulsions of various medicinal substances
intended to be rubbed on the skin
Sprays • Fixed oils, alc or hydroalc as vehicles
• Labels such as “For external use” or “Shake
• Aqueous or oleaginous solutions in the form of
well”
coarse droplets or as finely divided solids to be
• Applied to intact skin. Used as rubefacient or
applied topically, most usually to the
counterirritant
nasopharyngeal tract or to the skin.
• Oleaginous liniments are for massage
Aromatic Waters • Are never taken internally
• Emulsion liniments or insoluble-containing
• Clear, aqueous solutions saturated with volatile liniments must have a “Shake well” label
oils or other aromatic or volatile substances • They are prepared in the same manner as
• Used as perfuming or flavorant solutions, emulsions, or suspensions
Diluted Acids • Solvents for oleaginous substances are almond
oil, arachis oil, sesame oil, cottonseed oil, or
• Diluted acids are aqueous solutions prepared by volatile substances like wintergreen oil or
diluting the corresponding concentrated acids turpentine.
with purified water.
Collodions
• The strength of a diluted acid is generally
expressed on a percent weight –to-volume (% • are liquid preparations containing nitrocellulose
w/v) basis,. pyroxylin in a mixture of ethanol and ethyl ether
(25:1:3)
• used as topical protectives or as a topical drug
vehicle.
• made "flexible" by the addition of castor oil and
“waterproof’ by camphor (3%,2%)
• Highly flammable, volatile. Label should
indicate for “External use only”

Glycerins

• Also known as Glycerites are solutions in

composed of no less than 50% glycerin by
weight.
• They are extremely viscous and are rarely used
in practice and are generally limited to use in
topical products

Liquid Preparations Prepared by Extraction

Processes

Fluidextracts

• Are liquid preparations of vegetable drugs by

percolation
• Alcohols are used as solvents, preservative or
both
• Bcoz concentrated, they are too potent and bitter.
This made them modified by the addition of
flavorants or sweetening agents before use or
used as drug source of other liquid dosage forms
like syrups

Extracts

• Are concentrated preparations of vegetable or

animal drugs obtained by removal of the active
constituents by the menstruum
• Are potent and usually between 2 and 6 times as
potent as the crude drug
• Percolation is the method used followed by
distillation for reduction of volume

3 forms of Extract

• Semi-liquid Extracts
o Or those with syrupy consistency
prepared without the intent of
removing all or even most of the
menstruum
• Pilular
o Or solid extracts of a plastic consistency
prepared with nearly all of the menstruum
removed
• Powdered Extracts
o Prepared to be dry by the removal of all of
the menstruum