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Learning Objectives
Upon completion of this lecture, you should be able to:
• Define, give an example of, and/or classify examples of each of the
followings Solute, Solvent, Syrups, Mucilages
• State at least six (6) pharmaceutical uses or applications of
solutions.
• Identify commonly used pharmaceutical solvents.
• Identify at least three (3) necessary criteria of pharmaceutical
solvents.
• Define simple syrups, flavoring syrups, medicinal syrups, syrup
USP, and caramelization.
• List three (3) methods of preparing syrups.
• Describe and demonstrate how to prepare a syrup by the "agitation
with heat" method.
• Describe alternative formulations for "syrups" prepared with nonsugar sweeteners and state their advantages and limitations.
Advantages of Solutions
(1) Easier to swallow therefore easier for:
children - old age - unconscious people.
(2) More quickly effective than tablets and capsules.
(3) Homogenous therefore give uniform dose than
suspension or emulsion which need shaking.
(4) Dilute irritant action of some drugs (aspirin, Kl, KBr)
minimize adverse effects in the GIT like KCl.
Disadvantages of Solutions
(1) Difficult to mask unpleasant tastes
(2) Bulky, difficult to transport and prone to
container breakages
(3) Technical accuracy needed to measure
dose on administration
(4) Measuring device needed for
administration
(5) Some drugs poorly soluble
Classification of Solutions according to
route of administration
• Orally: Syrups, elixirs, drops
• In mouth and throat: Mouth washes, gargles,
throat sprays.
• In body cavities: Douches, enemas, ear drops,
nasal sprays.
• On body Surfaces: Collodions, lotions.
Classification of Solutions
According to Vehicle
(a)
Aqueous solutions
(b) Non-aqueous solutions
• Aqueous Solutions
• Aqueous solutions are homogeneous mixtures that are prepared by
dissolving a solid, liquid or gas in an aqueous medium (vehicle).
• Vehicle: This may be water, aromatic water or extracts
Pharmaceutical Applications of
Solutions
Solutions have a wide variety of uses in the
pharmaceutical industry:
• They are used therapeutically as vehicles for oral,
parenteral, topical, otic, ophthalmic, and nasal products.
• They are also used as flavorings, buffers,
preservatives, and suspending agents for a variety of
liquid dosage forms.
Solutions
• A solution is a thermodynamically stable, onephase system composed of 2 or more
components, one of which is completely
dissolved in the other.
• The solution is homogeneous because the
solute, or dispersed phase, is dispersed
throughout the solvent in molecular or ionic
sized particles.
Solutions
• The solute is the component present in the
smallest amount
• and the solvent is the larger
liquid
component.
• Water is nearly always considered the solvent.
• Pharmaceutical solutes may include
 active drug components,
 flavoring or coloring agents,
 preservatives,
 stabilizers or buffering salts.
Solutions
• Water is the most common solvent for
pharmaceutical solutions, but
• ethanol,
• glycerin,
• propylene glycol,
• isopropyl alcohol or other liquids may be used,
depending on the product requirements.
• To be an appropriate solvent, the liquid
must
• dissolve the drug and other solid ingredients at the
desired concentration,
• be nontoxic and safe for ingestion or topical application,
and be aesthetically acceptable to the patient in terms
of appearance, aroma, texture, and/or taste.
Solubility
• Solubility: it is the concentration of a solute in a
saturated solution at a certain temperature.
• A saturated solution: is one in which an equilibrium
is established between dissolved and undissolved
solute at a definite temperature
b) The USP lists the solubility of drugs as the
number of ml of solvent in which 1
g of solute will dissolve. E.g. 1g of boric acid
dissolves in 18 mL of water, and in 4 mL of
glycerin.
3. Solubility expressions
c) Substances whose solubility values are not
known are described by the following terms:
Solubility
• The solubility of a drug in a given solvent
is largely a function of the polarity of the
solvent.
• Polar solvents (water, glycols, methyl &
ethyl alcohol), dissolve ionic solutes &
other polar substances
• Non polar solvents can dissolve non polar
solutes
• i.e. like dissolves like
Quiz
1. The statement ‘like dissolves like’
means that solutes best dissolve in
solvents of similar……
• pH
• Properties
• Component
• Polarity
WATER
• WATER
• Water is used both as vehicle and as a solvent for the desired
flavoring or medicinal ingredients.
• Advantages: Tasteless, odorless, lack of pharmacological activity,
neutral and very cheap
• Tap Water
• It is not permitted to use tap water for the dispensing of
pharmaceutical dosage forms due to its possible bacterial
contamination and the presence of dissolved salts that destroy the
active ingredients or enhance their decomposition.
• Freshly Boiled and Cooled Water
• Boiling is seldom used to destroy vegetative bacteria. But, on
storage for long time spores may yield vegetative microorganism.
WATER
• Purified Water
• Must be used for most pharmaceutical operations and in all the tests
and assays.
• Such water is prepared by distillation, deionization or reverse
osmosis.
• "Hard" waters are those that contain the Ca and Mg cations.
• “Alkaline" waters are those that contain bicarbonates as the major
impurity.
• Ultraviolet energy, heat or filtration (Millipore filtration) can be used
to remove or kill the microorganisms present in the water.
• Water for injection
• Must be used for the formulation of parental solutions.
• It is obtained by sterilizing pyrogen-free distilled water.
Aqueous pharmaceutical
solutions
• Syrups are concentrated, viscous,
sweetened, aqueous solutions e.g. Syrup
USP, Wild Cherry Syrup USP.
• Aromatic waters are saturated solutions
of volatile oils in water and are used to
provide a pleasant flavor or aroma, e.g.
Peppermint Water, USP.
Aqueous pharmaceutical
solutions
• Mucilages are thick, viscous
macromolecular solutions produced by
dispersing vegetable gums in water.
• They are commonly used as suspending
or thickening agents, e.g. Acacia
Mucilage; Tragacanth Mucilage.
• Aqueous acids are dilute aqueous
solutions of acids (usually < 10%), e.g.
Diluted HCl, USP.
Methods of Preparation of
Solutions
(a) Simple Solution
(b) Solution by Chemical Reaction
(c) Solution by Extraction
Methods of Preparation of
Solutions
(a) Simple Solution
• Solutions of this type are prepared by dissolving
the solute in a suitable solvent (by stirring or
heating).
• The solvent may contain other ingredients which
stabilize or solubilize the active ingredient e.g.
solubility of Iodine is 1: 2950 in water however, it
dissolves in presence of KI due the formation of
more soluble polyiodides (KI.I2 KI.2I2 KI.3.I3
KI.4I4) [ Strong Iodine Solution USP (Lugol's
SoIution)].
Methods of Preparation of
Solutions
(b) Solution by Chemical Reaction
• These solutions are prepared by reacting two or
more solutes with each other in a suitable
solvent.
(c) Solution by Extraction
• Plant or animal products are prepared by
suitable extraction process.
• Preparations of this type may be classified as
solutions but more often, are classified as
extractives.
Additives (Excipients)
Buffers
• A buffer is a solution that resists change in pH
when a small amount of an acid or base is
added or when solution is diluted.
• A Buffer solution consists of a mixture of weak
acid and its salt or weak base and its salt.
Examples:
• NaAc + HAc
• NH4Cl + NH4OH
Additives (Excipients)
Buffers
• Buffers were added to adjust the pH of
solutions. Why?
1. solubility
• Most drugs are weak acids or weak bases
• Ionization (dissociation) of these drugs depends
on pH
• Dissociated form of weakly acidic or basic drug
has a higher solubility than undissociated form
Quiz
2. The solubility of Compound A is (See the Figure)
a) Compound A is 550 fold more soluble than compound B
b) Compound B is 550 fold more soluble than compound A
c) The two compounds have same solubility
d) The two compounds were insoluble
•
A
B
Additives (Excipients)
1) Buffers
• Buffers were added to adjust the pH of
solutions. Why?
2. Therapeutic response
• Undissociated form of weakly acidic or basic
drug often has a higher therapeutic activity than
that of the dissociated form. Why?
• Undissociated form is lipid soluble and can
penetrate body membranes readily compared to
ionic form
Additives (Excipients)
1) Buffers
Buffers were added to adjust the pH of
solutions. Why?
3. Stability
• Choose the pH of maximum stability
Additives (Excipients)
1) Buffers
Buffers were added to adjust the pH of solutions. Why?
4. Tissue irritation
large pH difference between the solution being
administered and the physiologic environment in
which it is used should be minimal to reduce
tissue irritation.
Eye is a delicate tissue, therefore it is important
to adjust the pH of ophthalmic preparations and
large parenteral solutions
Additives (Excipients)
2) Isotonicity modifiers
 Solutions that have the same osmotic pressure as the
body fluid are said to be isotonic with the body fluid.
 A 0.9 percent solution of sodium chloride, or a five
percent solution of dextrose, are isotonic with our body
fluids
solutions should be made isotonic
– To avoid crenation or hemolysis of RBC's, to avoid
pain and discomfort if solutions are injected or
introduced into the eyes and nose.
•
Most widely used isotonicity modifiers are: dextrose
and NaCl
Additives (Excipients)
3) Viscosity enhancement
• It is difficult for aqueous-based topical
solutions to remain on the skin or in the
eye (why?) therefore low concentrations of
jelling agents are added to increase the
viscosity
Additives (Excipients)
4) Preservatives
Solution may become contaminated for a
number of reasons:
• Raw materials used in the manufacture of
solutions are excellent growth media for
bacterial substances such as gums, dispersing
agents, sugars and flavors
• Equipment, environment and personnel
contribute to product contamination.
• Consumer use may result in the introduction of
microorganism.
 a preservative should be added to the
product
Preservatives
•
Preservatives may be used alone or in combination to prevent the
growth of microorganisms.
• Examples
•
•
•
•
•
•
Ethanol
Propylene glycol
Acids
Benzoic acid and asorbic acid
Esters
Parabens are esters (methyl, ethyl, propyl and butyl) of
p-hydroxybenzoic acid.
• Quaternary Ammonium Compounds
• Benzalkonium chloride
Antioxidants
• Vitamins, essential oils & almost all fats and oils can be
oxidized. Oxidation reaction can be initiated by:
1. heat: maintain oxidizable drugs in a cool place
2. light: use of light- resistant container
3. heavy metals (e.g. Fe, Cu): effect of trace metals can
be minimized by using citric acid or ethylenediamine
tetraacetic acid (EDTA) i.e. sequestering agent .
• Antioxidants as propyl & octyl esters of gallic acid,
tocopherols or vitamin E, sodium sulfite, ascorbic acid
(vit. C) can be used.
Sweetening agents
• Sucrose is the most widely used sweetening
agent.
•
Advantages: Colourless, highly water soluble,
stable over a wide pH range (4-8).
• Increase the viscosity, masks both salty and
bitter taste, has soothing effect on throat.
• Polyhydric alcohols (sorbitol, mannitol and
glycerol) possess sweetening power and can be
used for diabetic preparations.
Flavors and perfumes
• Mask unpleasant taste or odour
• Enable the easy identification of the
product.
• Natural products: fruit juices, aromatic oil
(peppermint, lemon)
• Artificial perfumes are cheaper, more
readily available and more stable than
natural products.
Pharmaceutical Solutions
•
•
•
•
•
•
•
•
•
•
Aqueous
Douches
Enemas
Gargles
Mouthwashes
Nasal washes
Juices
Sprays
Otic solutions
Inhalations
Sweet &/or Viscid
Nonaqueous
Syrups
Honeys
Mucilages
Jellies
Elixirs
Spirits
Collodions
Glycerins
Liniments
Oleo Vitamin
Sweet Pharmaceutical
Preparations
• These include Syrups, Honeys, Mucilages, and Jellies.
• All of these preparations are viscous liquids or semisolids.
• The sweetness and viscid appearance are given by sugars, polyols,
or polysaccharides (gums).
• SYRUPS
• Syrups are concentrated solutions of sugar such as sucrose in water
or other aqueous liquid.
• simple syrup: when water is used alone for making syrup.
• medicated syrup: when the aqueous preparation contains
some added medicinal substance
• flavored syrup: which contains aromatic or pleasantly
flavored substances and is intended to be
used as a vehicle or flavor for prescriptions
Sweet Pharmaceutical
Preparations
•
•
•
Polyols (e.g. glycerin or sorbitol) may be added to
- retard crystallization of sucrose or
- increase the solubility of added ingredients.
Alcohol often is included as
- preservative
- solvent for volatile oils.
Syrups possess remarkable masking properties for bitter and saline drugs.
•
It is important that the concentration of sucrose approaches but not
quite reach the saturation point, WHY?
•
In dilute solutions sucrose provides an excellent nutrient for molds,
yeasts, and other microorganisms.
In concentration of 65 % by weight or more the solution will retard the
growth of such microorganisms.
A saturated solution may lead to crystallization of a part of the sucrose
under conditions of changing temperature.
•
•
Sweet Pharmaceutical
Preparations
• Invert Syrup:
•
•
•
•
•
•
It is prepared by hydrolyzing sucrose with hydrochloric acid and neutralizing
the solution with Ca or Na carbonate.
C12H22O11
heat & acid
2 C6H12O6
Sucrose
Invert sugar
(dextrose and levulose)
The invert syrup, when mixed in suitable proportions with syrup, prevents
the deposition of crystals of sucrose under most conditions of storage.
The levulose formed during inversion is sweeter than sucrose; therefore the
resulting syrup is sweeter than the original syrup.
When syrup is overheated it caramelizes
Dextrose-Based Syrups
• Dextrose may be used as a substitute for sucrose
•
•
•
•
(WHEN?) in syrups containing strong acids in order
to eliminate the discoloration associated with inversion.
Dextrose forms a saturated solution in water at 70% w/v,
which is less viscous than simple syrup.
It dissolves more slowly than sucrose and is less sweet.
Preservatives are required to improve the keeping
qualities of such syrups.
Glycerin is added in 30% to 45% v/v as preservative.
Sorbitol-Based Syrups
• Sorbitol which is hexahydric alcohol made by hydrogenation of
glucose has been used in the preparation of syrup.
• It is used mostly in the form of a 70% w/w aqueous solution.
• Sorbitol solution is not irritating to the membrane of the mouth and
throat and does not contribute to the formation of dental carries.
• Sorbitol is metabolized and converted to glucose; however, it is not
rapidly absorbed from the GlT as sugars.
• No significant hyperglycemia has been found ; it may be used as
component of non-nutritive vehicles.
• Preservative should be used in solution containing less than 60%
w/w sorbitol.
• It is chemically stable and inert with respect to drugs and other
ingredients used in pharmaceutical preparations.
Artificial Syrups (Non-Nutritive
Syrups)
• intended as substitutes for syrups and
are to be administered to persons
who must regulate their sugar and/or
calorie intake accurately. e.g. persons
suffering from diabetes mellitus.
• An example of non-nutritive artificial
sweeteners is aspartame & saccharin
•
Preparation of Simple Syrup
• (a) Solution with heat
•
•
•
•
•
•
•
This is the usual method of making syrups:
– in the absence of volatile agents or those injured by heat
– when it is desirable to make the syrup rapidly.
The sucrose is added to the purified water or aqueous solution and heated
until dissolved
sufficient purified water added to make the desired weight or volume.
Excessive heating in the preparation of syrups must be avoided to prevent,
caramelization
Syrups cannot be sterilized by autoclaving without caramelization (yellow
color).
The specific gravity of syrup is an important property to identify its
concentration.
Syrup has a specific gravity of about 1.313, which means that each 100 ml
of syrup weighs 1313 g.
Preparation of Simple Syrup
• (b) Agitation without Heat
• This process is used in those cases where heat
would cause loss of valuable volatile
constituents.
• The syrup is prepared by adding sucrose to the
aqueous solution in a bottle of about twice the
size required for the syrup.
• This permits active agitation and rapid solution.
• The stoppering of the bottle is important, as it
prevents contamination and loss during the
process.
HONEYS
• Are thick liquid preparations.
• At one time, before sugar was available,
honey was used as a base, instead of
syrup.
• There are few official preparations
containing honey. e.g. Oxymel, or" acid
honey "'is a mixture of acetic acid, water
and honey