SOLUTIONS

PHARM.D 3rd Semester

Definition
• A solution is a homogenous mixture that is prepared
by dissolving a solid, liquid or gas in another liquid
and represents a group of preparations in which the
molecules of solute are molecularly dispersed among
those of solvent.

• 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”
…
• Solute: substance being dissolved
Solvent: medium in which the solute is dissolved

• Most pharmaceutical solutions are unsaturated with

solute i.e. the concentration of solute in the solution
is below its solubility limit

• Solutions used as a dosage form include solutions for

internal, external as well as parenteral administration
Advantages of Solution
• Advantages of solutions include:
1. Solutions can be designed for various
routes of administration
2. Drugs in solution are more homogenous
3. Easier to swallow
4. Drug is rapidly absorbed
5. Immediately diluted by gastric contents
which reduce irritation to the gastric
mucosa
Disadvantages of Solution
• The disadvantages of solutions compared
with other dosage forms include:
1. Poor drug stability or more rapid drug
degradation
2. Many drugs are poorly water soluble.
Their formulation as a solution is
challenging
3. Liquid dosage forms are bulky and
difficult to store and transport
4. Packaging is expensive
Classification of solutions
• Classification on the basis of nature of formulation/
dosage form
• Classification on the basis of route of administration
• Classification on the basis of method of preparation
CLASSIFICATION ON THE BASIS OF
NATURE OF FORMULATION
• Syrup
• Elixir
• Spirits
• Aromatic water
• Tinctures
• Lotion
• Liniments
• Collodion
• Injections
• Enema
• Mouthwashes
CLASSIFICATION ON THE BASIS OF
ROUTE OF ADMINISTRATION
ROUTE OF REQUIREMENTS OF THE SOLUTION
ADMINISTRATION
ORAL Oral solutions are aqueous formulations. They must be
palatable to be acceptable to the patients. Flavoring,
coloring and sweetening agents are added to enhance their
appearance and taste.
Examples: syrups, elixirs, tinctures etc
TOPICAL Topical solutions are those which are applied externally
i.e. to the skin, nails or hair. The vehicle for topical
preparations may be aqueous or non-aqueous.
Examples: lotions, liniments, collodions etc
OTIC Otic solutions are instilled in the outer ear to exert a local
effect. These solutions may be aqueous or non-aqueous.
These solutions does not need to be isotonic as they are
external preparations
ROUTE OF REQUIREMENTS OF THE SOLUTION
ADMINISTRATION

OPTHALMIC These solutions are used in the eye and must be

manufactured sterile as the product is to come in contact
with tissues that are very sensitive to contamination. A
multi-dose opthalmic solution must contain antimicrobial
preservatives.
Ideally an opthalmic solution must be isotonic.
Examples: eye drops, eye lotion
NASAL Nasal solutions are aqueous formulations used for local or
systemic drug delivery.
Multi-dose nasal solutions require preservatives
Nasal solutions are usually isotonic to nasal fluids
Examples: nasal drops, nasal sprays
PULMONARY Inhaled solutions are administered by pressurized metered-
dose inhalers or by nebulizers for local or systemic effect.
Solutions of drug and excipients dissolved in liquefied
propellents are used in pressurized metered-dose inhalers.
Solutions used in nebulizers are aqueous formulations.
ROUTE OF REQUIREMENTS OF THE SOLUTION
ADMINISTRATION
PARENTERAL Parenteral refers to the injectable routes of
administration. Parenteral solutions must be sterile
and pyrogen-free
Intravenous solutions must be aqueous
Intamuscular and subcutaneous solutions can be
aqueous or non-aqueous
Parenteral solutions must be isotonic when large
volumes are administered (IV Infusion)
RECTAL Solution enemas are usually administered for local
or systemic drug action
Enemas can be aqueous or oily solutions
CLASSIFICATION ON THE BASIS OF
METHOD OF PREPARATION
• On the basis of method of preparation solutions are
classified into
1. Simple solutions
2. Complex solutions

• Simple solutions: simple solutions are prepared by

simple mixing the ingredients that have high affinity for
each other.
• Complex solutions: complex solutions are prepared by
dissolving the ingredients with the help of heat, agitation
etc.
PREPARATION OF SOLUTION:
• In formulating or compounding a pharmaceutical
solution, the pharmacist must use information on the
solubility and stability of each solute with regard to
the solvent or solvent system. Combinations of
medicinal or pharmaceutical agents that will result in
chemical and/or physical interactions affecting the
therapeutic quality or pharmaceutical stability of the
product must be avoided.
PREPARATION OF SOLUTION:
• In most instances, especially for solutions to be taken orally, used
intranasal, ophthalmically, or injected, water is the preferred solvent.

• When water is used as the primary solvent, commonly an auxiliary

solvent is also employed to augment the solvent action of water or
to contribute to a product’s chemical or physical stability.

• Alcohol, glycerin, and propylene glycol, perhaps the most widely

used auxiliary solvents

• Other solvents, such as acetone, ethyl oxide, and isopropyl alcohol,

are too toxic to be permitted in pharmaceutical preparations to be
taken internally
PREPARATION OF SOLUTION:
• Nature of solubility enhancer depends on drug
molecule and route of administration.

• The strength of pharmaceutical preparations are

usually expressed in terms of percent strength,
although for very dilute preparations, expressions of
ratio strength may be used. These expressions and
examples are shown in Table 13.4.
Excipients used in Pharmaceutical Solutions

Excipients Examples of Excipients

Co-solvents Ethanol, glycerol, propylene glycol

Flavoring agents Vanilla, raspberry, orange oil, lemon oil, menthol

Coloring agents A coloring agents should correlate with flavoring agent e.g. green
with mint flavor, red with cherry flavor
Sweeteners Sucrose, sorbitol, mannitol, saccharin sodium etc
Sweetened but sugar-free preparations containing aspartame are
available for diabetic patients
Antimicrobial Benzalkonium chloride, benzyl alcohol, chlorobutanol, combinations
preservatives of parabens (methyl, propyl, butyl)
Antioxidants Sodium sulfite, sodium metabisulfite, ascorbic acid

Chelating agents Sodium edetate

pH adjusters Acids, e.g. citric acid, buffers

Alkalis, e.g. sodium hydroxide buffers
Isotonicity adjusters Sodium chloride, potassium chloride, dextrose, glycerol

Viscosity enhancers Hydroxyethyl cellulose, povidone, dextran, carbomer 940

PREPARATION OF SOLUTION:
• Solutions may be prepared by the following methods:

• PREPARATION OF SIMPLE SOLUTION:

 Simple solutions are prepared by simple mixing of the ingredients
that are rapidly soluble so when mixed they form a simple solution.
 Most solutions are prepared by simple mixing of the solutes with
the solvent.
 In this method the solute is dissolved in most of the solvent, mixing
until it is dissolved, then a sufficient amount of solvent is added to
bring solution up to the final volume.

• Examples:
 Sodium phosphate oral solution USP, Strong iodine solution USP.
PREPARATION OF SOLUTION:
• PREPARATION OF COMPLEX SOLUTION:
 Some chemical agents in a given solvent require an extended time to
dissolve. To hasten dissolution, a pharmacist may employ one of several
techniques, such as applying heat, reducing the particle size of the solute,
using a solubilizing agent, and/or subjecting the ingredients to vigorous
agitation.

1) Heat:
 Most chemical agents are more soluble at elevated temperatures than at
room temperature or below because an endothermic reaction between the
solute and the solvent uses the energy of the heat to enhance dissolution.

 Great care is required during preparation because for many medicinal

agents are destroyed at elevated temperatures and the advantage of rapid
solution may be completely offset by drug deterioration.
PREPARATION OF SOLUTION:
2) Reduction of particle size:
 The particle size of the solute plays an important role in the
preparation of solution. The reduced particle size increases the
surface area of the solute and thus is easily solubilized.

 This may be accomplished by comminution (grinding a solid to a

fine state of subdivision) with a mortar and pestle on a small
scale or industrial micronizer on a larger scale.

3) Addition of solubilizing agent:

 Solubilizing agent is the specie that tends to keep the solute and
solvent in the solution form.
 It increases he solubility of solute in solvent.
PREPARATION OF SOLUTION:
4) Vigorous shaking/agitation :
 If the powder is placed in a suitable vessel (e.g., a
beaker, the graduated cylinder, bottle and is stirred
or shaken, as suited to the container with a portion
of a solution).
 this helps save time as the rate of solution formation
may be increased by the continued circulation of
fresh solvent to the drug’s surface.
PREPARATION OF SOLUTION:
• PREPARATION OF SOLUTION BY CHEMICAL
REACTION:
 Solution by chemical reaction are prepared by reacting two or
more solutes with each other in a suitable solvent
 Example: Aluminum Subacetate Topical Solution USP.

• PREPARATION OF SOLUTION BY EXTRACTION:

 Drugs or pharmaceutically important substances present in plant
or animal sources are often extracted with water or with water
containing other substances.
 The products prepared by this method may be classified as
solutions but more often are classified as extracts because they
are prepared by process of extraction.
ORAL SOLUTIONS AND PREPARATIONS
FOR ORAL SOLUTION
“Solutions that are intended for oral administration are called as
oral solutions.”
• Most solutions intended for oral administration contain flavorants
and colorants to make the medication more attractive and palatable.

• The formulation pharmacist must be wary of chemical interactions

between the various components of a solution that may alter the
preparation’s stability and/or potency.

• Liquid pharmaceuticals for oral administration are usually

formulated such that the patient receives the usual dose of the
medication in a conveniently administered volume, as 5 (one
teaspoonful), 10, or 15 mL (one tablespoonful).
…
• Few solutions have unusually large doses, for
example, Magnesium Citrate Oral Solution, USP,
with a usual adult dose of 200 mL. On the other hand,
many solutions for children are given by drop with a
calibrated dropper usually furnished by the
manufacturer in the product package.
DRY MIXTURES FOR SOLUTION
• A number of medicinal agents, particularly certain
antibiotics, e.g., penicillin V, have insufficient stability in
aqueous solution to meet extended shelf-life periods.

• Commercial manufacturers of these products provide them

to the pharmacist in dry powder or granule form for
reconstitution with a prescribed amount of purified water
immediately before dispensing to the patient.

• The dry powder mixture contains all of the formulative

components, including drug, flavorant, colorant, buffers,
and others, except for the solvent
DRY MIXTURES FOR SOLUTION
• The dry mixture is converted into solution by adding a
specified amount of purified water, also called as
reconstituted solution.

Expiry and storage:

• Once reconstituted, the solution remains stable when stored
in the refrigerator for the labeled period, usually 7 to 14
days, depending on the preparation
• In case the medication remains after the patient completes
the course of therapy, the patient should be instructed to
discard the remaining portion, which would be unfit for use
at a later time
DRY MIXTURES FOR SOLUTION
Examples:
Examples of dry powder mixtures intended for
reconstitution to oral solutions are the following:
• Cloxacillin Sodium for Oral Solution, USP (Teva),
an anti-infective antibiotic
• Penicillin V Potassium for Oral Solution, USP
(Veetids, Geneva), an anti-infective antibiotic
• Potassium Chloride for Oral Solution, USP
(K- LOR, Abbott), a potassium supplement
ORAL REHYDRATION
SOLUTIONS
• These solutions are used orally for rehydration i.e. the regain of
water and other essential electrolytes that are lost by
dehydration and are known as “Oral rehydration solutions”

• A typical oral rehydration solution contains electrolytes that are

essential for normal body functions. These formulations are
available in liquid or powder packet form for reconstitution.

• Rapid fluid loss associated with diarrhea can lead to

dehydration and ultimately death in some patients, particularly
infants. More than 5 million children younger than 4 years of
age die of diarrhea each year worldwide.
..
Diarrhea:
it is characterized by an increased frequency of loose, watery stools, and
because of the rapid fluid loss, dehydration can be an outcome.

• Diarrhea is a normal physiologic body response to rid itself of a noxious or

toxic substance, such as rotavirus or Escherichia coli.

• During diarrhea, the small intestine secretes far more than the normal
amount of fluid and electrolytes, and this simply exceeds the ability of the
large intestine to reabsorb it.

• The loss of fluid during diarrhea is accompanied by depletion of sodium,

potassium, and bicarbonate ions; if severe, the loss can result in acidosis,
hyperpnea, and vomiting as well as hypovolemic shock. If continuous,
bouts of vomiting and diarrhea can cause malnutrition as well.
..
 Treatment:
The dehydration due to diarrhea may be treated
with:
1. Oral rehydration solutions (ORS)
2. Anti-diarrheal drugs
3. Parenterally administered electrolyte solutions
..
 Oral rehydration solutions:
• Oral rehydration solutions are usually effective in treatment of
patients with mild volume depletion, 5% to 10% of body weight

• These are available OTC and are relatively inexpensive, and their use
has diminished the incidence of complications associated with
parenterally administered electrolyte solutions.

• Therapy with these solutions is based on the observation that glucose

is actively absorbed from the small intestine, even during severe
diarrhea. This active transport of glucose is advantageous because it
is coupled with sodium absorption. Sodium absorption promotes
anion absorption, which in turn promotes water absorption to short-
circuit dehydration.
..
• A liter of typical oral rehydration solution contains 45 mEq of
Na+ , 20 mEq K+, 35 mEq , 30 mEq , and 25 g dextrose.

• Reconstitution: These formulations are available in liquid or

powder packet form for reconstitution. It is important that the user
add the specific amount of water needed to prepare the powder
forms.

• These products should not be mixed with or given with other

electrolyte-containing liquids, such as milk or fruit juices

• Each sachet should be dissolved in 1 liter water before use and is

taken orally within 24 hours. After this time solution is discarded
and new solution is prepared.
..
• The pharmacist must discourage the production of
homemade versions of electrolyte solutions.

• Examples:
Commercial ready-to-use oral electrolyte solutions to
prevent dehydration or achieve rehydration include:
• Pedialyte Solution
• Rehydralyte Solution
• Peditral solution
ORAL COLONIC LAVAGE
SOLUTION
• The solution which is taken orally and is used for cleaning
of bowel for colonoscopy or endoscopy is known as “Oral
Colonic Lavage Solution”.

• Traditionally, preparation of the bowel for procedures such

as a colonoscopy consisted of administration of a clear
liquid diet for 24 to 48 hours preceding the procedure,
administration of an oral laxative such as magnesium citrate
or bisacodyl the night before, and a cleansing enema
administered 2 to 4 hours prior to the procedure.
ORAL COLONIC LAVAGE
SOLUTION
• An alternative method to prepare the gastrointestinal tract has been
devised. This procedure requires less time and dietary restriction and
obviates the cleansing enemas.

• This method entails oral administration of a balanced solution of

electrolytes with polyethylene glycol (PEG-3350-Electrolyte Solution),
i.e., PEG-ES.

• Before dispensing it to the patient, the pharmacist reconstitutes this powder

with water, creating an iso-osmotic solution having a mildly salty taste.

• A large volume of this solution can be administered without a significant

change in water or electrolyte balance
ORAL COLONIC LAVAGE
SOLUTION
• The formulation of PEG-3350 colonic lavage solution is as follows:
PEG-3350 236.00 g
Sodium sulfate 22.74 g
Sodium bicarbonate 6.74 g
Sodium chloride 5.86 g
Potassium chloride 2.97 g

• The recommended adult dose of this product is 4 L of solution before the

gastrointestinal procedure.

• The patient is instructed to drink 240 mL of solution every 10 minutes

until about 4 L is consumed.

• The patient is advised to drink each portion quickly rather than sipping it
continuously. Usually, the first bowel movement will occur within 1 hour.
ORAL COLONIC LAVAGE
SOLUTION
• Ideally, the patient should not have taken any food 3
to 4 hours before beginning to take the solution.

• In no case should solid foods be taken by the patient

for at least 2 hours before the solution is
administered.

• Storage: The product must be stored in the

refrigerator after reconstitution, and this aids
somewhat in decreasing the salty taste of the product.