LIQUID PREPARATIONS PART I Flashcards
Liquid Preparations may be
dispensed in one of 3 ways
-original container
-Repacking a bulk product
-Compounding the solution, suspension or
emulsion in the dispensary
Classification of Liquid Preparation
- Solutions (single phase system)
- Mixtures (two phase system)
- Galenicals (extractives)
- Sterile Products
Oral solutions are ______________ mixtures of one or more solutes
dissolved in suitable solvent or mixture of
mutually miscible solvents
homogenous;
These are homogenous mixtures of one or more solutes
dissolved in suitable solvent or mixture of
mutually miscible solvents
Oral solutions
classified on the basis of physical
properties, method of preparation, use and
type of ingredients
Oral solutions
Oral solutions areclassified on the basis of ________, _________, ________
classified on the basis of physical
properties, method of preparation, use and
type of ingredients
Examples of oral solutions
Syrup, Elixir, Spirit, Aromatic water, tincture,
fluidextract
ADVANTAGES OF SOLUTIONS AS AN ORAL DOSAGE FORM
-Liquids are easier to swallow than solids and
are therefore particularly acceptable for
pediatric and geriatric use
-A drug must usually be in solution before it can
be absorbed
-Solution is a homogenous system and
therefore the drug will be uniformly distributed
throughout the preparation
DISADVANTAGES OF SOLUTIONS AS AN ORAL DOSAGE FORM
-Liquids are bulky and therefore inconvenient to transport and store
-Stability of ingredients in aqueous solution is often poorer than if
formulated as a tablet or capsule
-Solutions often provide suitable media for the growth of
microorganisms and may therefore require the incorporation of a
preservative
-Many liquid preparations are designed so that the normal dosage
of the drug is present in 5mL, or a multiple of 5 mL, of the product
-The taste of a drug, which is usually unpleasant, is always more
pronounced when in solution than in solid form
The design and formulation of oral solutions involves the combination of ingredients with _____________
_________ to enhance the __________ of effectiveness of
the product
medicinal agents; acceptability
Several considerations in the design and formulation of oral solutions:
-concentration of the drug
-solubility of the drug, selection of the liquid vehicle
-physical and chemical stability
-preservation of the
preparation
-appropriate excipients such as buffers,
solubilizers, sweetening agents, viscosity controlling
agents, color and flavors
Successful design and formulation of liquids, as well as other dosage forms, requires both ________ and
______________ acuity
scientific and pharmaceutical acuity
concentration of the
dissolved solute in a saturated solution
Solubility
Is solubility qualitative or quantitative?
Quantitative
drugs are present in solution at
_____________ concentrations, otherwise, the drug may
crystallize as a result of changes in temperature or by
“_____________” from other ingredients or particulate matter present
unsaturated; seeding
Solubility is associated with the Effects of _________, effect of _____________, effect of
______________
pH, molecular structure, temperature
process by which the apparent
solubility of a poorly water soluble substances
is increased
Solubilization
Solubilization Techniques
addition of cosolvent, salt
formation, prodrug method, micellization
Drug substances in general are __________ (more/less) stable in liquid media
than in the solid dosage form.
less stable
consider both the pH solubility profile
and stability profile in order to select the optimum pH for
formulating the liquid oral dosage form
Chemical Stability
involves the formation of precipitate, less
soluble polymorph, adsorption of the drug substances onto
container surfaces, microbial and product appearance
Physical Stability
Solvent for aq solutions
Purified Water (water for injections)
obtained by deionization,
distillation, ion exchange, reverse osmosis,
filtration or other suitable procedures
Water
T/F: Although water is very widely used for inclusion
in pharmaceutical preparations, it may not be
possible to ensure complete solution of all
ingredients at all normal storage temperatures.
T
Water for
parenteral administration
Water for Injections, Bacteriostatic Water for
Injections, or Sterile Water for Injections
The acceptability of the product is a ___________ evaluation
and includes properties such as color, odor, taste and clarity
subjective
Major impurities in water are:
calcium, iron, magnesium, silica and sodium
Non-Aqueous solutions
- Fixed oils of vegetable origin
- Alcohols
- Polyhydric alcohols
- Dimethylsulphoxide
- Ethyl ether
- Liquid paraffin
When mixed with water, a ____________ ___________ is
formed capable of dissolving both alcohol-soluble and water-soluble substances, a feature especially useful for extraction and purification of active constituents from crude drugs and synthetic procedures
hydroalcoholic mixture;
Example of alcohols
Alcohol, diluted alcohol, rubbing alcohol, isopropyl
rubbing alcohol
Second most commonly used solvent in
pharmaceutical industry for many organic compounds
Alcohols
Recommended Alcohol content (OTC oral drugs) for children over 12 years of age and adults
10%
Recommended Alcohol content (OTC oral drugs) for children 6 to 12 years of age
5%
Recommended Alcohol content (OTC oral drugs) for children under 6 years of age
0.5%
In topical preparations, glycerin is used for its
___________ and _________ properties
humectant; emollient
Glycerin is used in pharmaceutical formulations including:
oral, otic, ophthalmic, topical and parenteral
preparations
Clear, syrupy liquid with a sweet taste and is miscible
with water and alcohol
Glycerin
Viscous liquid and miscible with water and alcohol
Propylene Glycol
In oral preparations, glycerin is used as ________,
____________ agents, ___________________ and
viscosity increasing agent
solvent; sweetening; antimicrobial preservatives;
Widely used as solvent, extractant, preservative in a
variety of liquid pharmaceutical formulations including parenteral
Propylene Glycol
Often used in place of glycerin
Propylene Glycol
As an antiseptic it is similar to ethanol, and against
molds it is similar to glycerin and only slightly less
effective than ethano
Propylene Glycol
__________ is used as carrier for emulsifiers and as vehicle for
flavors, as opposed to ____________, due to its lack of
____________
Propylene Glycol; ethanol; volatility
Miscellaneous Solvents
- Isopropyl myristate and isopropyl palmitate
- Dimethylformamide and dimethylacetamide
- Kerosene
- Xylene
- Glycofurol
Other Formulation Additives
- Buffers
- Density modifiers
- Isotonicity modifiers
- Viscosity enhancement
- Preservatives
- Reducing agents and antioxidant
- Sweetening agents
- Flavors and perfumes
- Colors
These are materials which, when dissolved in a solvent, will enable the solution to resist any change in pH should an acid or alkali be added
Buffers
Examples of buffers
Carbonates, citrates, gluconates, lactates, phosphates,
tartrates
Most body fluids has a
pH of 7.4
Although buffers ensure pH stability, the buffer system can effect other properties such as
solubility and kinetics
Can act as general-acid or general-base catalysts and
cause degradation of the drug substance
Buffers
pH and usual conc (%) of acetic acid and salt
ph 3.5-5.7, 1-2%
_________ strength contribution of the buffer systems can also effect stability.
Ionic
pH and usual conc (%) of Citric acid and a
salt
2.5-6 pH; 1-3%
pH and usual conc (%) of Phosphoric acid
salts
6-8.2 pH; 0.8-2%
Most widely used material for density
modification is ____________
DEXTROSE
pH and usual conc (%) of Glutamic acid
8.2-10.2 pH; 1-2%
Solutions of lower density than cerebrospinal
fluid will tend to ___________ after injection and those of
higher density will _________
rise; fall
It is rarely necessary to control the density of
solutions EXCEPT when formulating ___________
spinal anesthetics
Compounds contributing to the _____________ of a
product reduce the pain of injection in areas
with nerve ending
isotonicity
example of Viscosity Enhancement
Povidone, hydroxyethylcellulose, carbomer
alcohol content of __________% by weight in acid solutions and _____________% by weight, in alkaline solutions is sufficient to prevent microbial growth
15% by weight in acid solutions and
18% by weight, in alkaline solutions
may serve as tonicity contributors as
well as stabilizers for pH
Buffers
examples of Isotonicity Modifiers other than buffers
Dextrose and NaCl
Propylene glycol is used as solvent in oral solution and topical preparations, and it can function as a
preservatives in the range of ____________
15 to 30%
____________ concentrations of
gelling agents can be used to increase the
apparent viscosity of the product
low
alcohols used in lower
concentrations (about 1%) as preservatives
Chlorobutanol and phenylethyl alcohol,
acid that has low solubility in water,
inhibitory action varies from 0.1-0.5%, activity
depends on the pH of the medium because
only the undissociated acid has antimicrobial
properties
Benzoic acid
useful as preservatives when it is used as
solvent, however, it does need a relatively high
concentration, somewhat greater than 15% to be
effective
Ethanol
criteria for acceptability of preservatives
- safety and lack of toxicity after oral intake
- must be soluble, stable and
microbiologically active - compatible with the active ingredients as well as other components of the formulation
Optimum activity of Benzoic acid occurs at pH
values below _________ and pH values above pH _______,
benzoic acid is almost inactive
4.5; 5
Most alcohol containing preparations such as _________, ________, ___________ are self preserving and will not require preservation
elixirs, spirits, tinctures
esters of p-hydroxybenzoic acid and
include methyl, ethyl, propyl, butyl derivatives
Parabens
When choosing a suitable preservative it must be ensured that:
_____________ of the preservative onto the container from the product
does not occur; and its efficiency is not impaired by the ___________ of the
solution or by the interactions with other ingredients
adsorption; pH
Too ____________ concentration of alcohols may result in incompatibilities in
suspension and emulsion system
high
Water solubility of the parabens _____________ as the
molecular weight increases, from 0.25% for the methyl
ester to 0.02% for the butyl ester
decreases
Esters are stable over a pH range _________
4-8
Has Broad spectrum of antimicrobial activity,and most
effective against molds and yeasts
Esters
Antimicrobial activity _____________ as the chain length of the alkyl moiety is increased but aqueous solubility
__________, therefore a mixture of parabens is frequently used to provide effective preservations
increases; decreases
Quarternary Ammonium Compounds Example
Benzalkonium Chloride
mixture consisting principally
of homologs C12H25 and C14H29. This preservative is
used at relatively low concentrations (0.002-0.02%)
Benzalkonium Chloride
Optimal activity of Quaternary Ammonium Compounds is met at pH ____________ and at _______ temperature
pH 4-10; Stable at room
temperature
Used as external preservatives
Quarternary Ammonium Compounds
Antifungal Preservatives
Butyl parabens, methyl paraben, ethyl
paraben, propyl paraben
Benzoic acid, potassium sorbate
Sodium benzoate, sodium propionate
Sorbic acid
Antimicrobial Preservatives
Benzalkonium chloride, benzathonium chloride,
benzyl alcohol, bronopo
Centrimide, cetylpyridinium chloride,
chlorhexidine, chlorobutanol, chlorcresol,
creso
Ethanol, glycerin, hexetidine, imidurea, phenol,
phenoxyethanol, phenylmercuric nitrate
Propylene glycol, thimerosa
Because of its cationic nature – it is incompatible with
many anionic compounds such as surfactants and can bind to nonionic surfactants
Quarternary Ammonium Compounds
examples of reducing agents
sodium metabisulfite, or antioxidants
such as butylated hydroxyanisole or butylated
hydroxytoluene
Polyhydric alcohols examples
Maltilol, lactilol,
isomalt, fructose, xylitol
For unit dose parenteral products, such as injections of nicotinamide and ascorbic acid, it is possible to use _____________ free from dissolved air and to replace the air in the headspace by nitrogen or another inert gases
Water for Injections
traditionally the most widely used sweetening
agents
Low molecular weight carbohydrates, such as sucrose
has the advantage of being colorless, very
soluble in water, stable over a pH range of about 4 – 8,
and by increasing the viscosity of fluid preparations,
will impart to them a pleasant texture in the mouth
Sucrose
The decomposition of pharmaceutical products by the oxidation can be controlled by the addition of ___________
reducing agents
also possess
sweetening power and can be included in the
preparations for diabetic use
Polyhydric alcohols
Sweetening agent with unpleasant aftertaste
Saccharin
Artificial sweetener examples
E954, E951, E950, E957,
E952, E959
Most commonly
used sweetening agent
Sucrose
Banned sweetening agent
Sodium
cyclamate
T/F: The simple use of sweetening agents may not be
sufficient to render palatable a product containing a
drug with a particularly unpleasant taste
T
Sweetening agent that is not very stable in
solution
aspartame
The inclusion of __________ has the additional advantage of
enabling the easy identification of liquid products
flavors
Particularly useful in pediatric formulation to ensure
patient compliance
Flavors and Perfumes
Suitable Masking Flavors for Salty
Apricot, butterscotch, liquorice, peach,
vanilla, maple, wintergreen
Suitable Masking Flavors for Sour
Citrus fruits, liquorice, raspberry
Suitable Masking Flavors for Bitter
Anise, chocolate, mint, passion fruit,
wild cherry
Suitable Masking Flavors for Sweet
Vanilla, fruits, berries
are pigments that are insoluble in water and which impart
color by dispersing and reflecting light, they are not used for
aqueous solutions
Lakes
are water soluble and exhibit color by transmitting light,
should be used at the lowest possible concentration required to
produce the desired color, higher concentration result in a dull
color
Dyes
present in trace amounts
dyes
coloring agents that should
be dissolved prior to mixing with the bulk of the formulations.
dye
