2. Liquid dosage forms are pourable pharmaceutical
preparations which contain a mixture of drug substance
and excipients dissolved or suspended in a suitable
solvent or mixtures of solvents.
They are designed to provide the maximum therapeutic
response in patients who have problem of swallowing
solid dosage forms and/or to produce rapid therapeutic
effects.
Liquid Dosage Form
3. 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” ( aqueous or
non –aqueous).
Certain solutions prepared to be sterile and pyrogen free and
intended for parenteral administration are classified as injections.
Solutions
4. A solution is a thermodynamically stable, one-phase 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.
Broadly defined, a solution may be any combination of solids,
liquids, and/or gases.
We will restrict our definition of pharmaceutical solutions to
those composed of a solid, liquid, or gas dissolved in a liquid
solvent.
Solutions
5. Generally, 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,
and stabilizers or buffering salts.
Solutions
6. 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 completely
dissolve the drug and other solid ingredients at the
desired concentration, be nontoxic and safe for ingestion
or topical application, and be acceptable to the patient
in terms of appearance, aroma, texture, and/or taste.
Solutions
7. Solutions can be formulated
for different routes 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.
8. Advantages of SoIutions
1. Easier to swallow
2. More quickly effective than solid dosage forms
3. Homogenous
4. The dose of the drug substance can be easily and conveniently
adjusted by measuring a different volume.
5. If given orally, liquid dosage forms are rapidly available for
absorption than tablets and capsules.
6. Liquid dosage forms (for oral use) are the most suitable dosage
form for patients who have difficulty taking tablets or capsules,
as might be the case with pediatric or geriatric patients.
7. They are attractive in appearance and gives beneficial
psychological effects.
8. Drugs with bitter and unpleasant taste can be given in
sweetened, colored and flavored vehicles.
9. Disadvantages of SoIutions
1. Liquid dosage forms are usually more susceptible to chemical
degradation when compared to solid dosage forms.
2. They are bulky and therefore inconvenient to transport and store.
3. Accidental breakage of the container results in loss of whole dosage
form.
4. The shelf-life of a liquid dosage form is often much shorter than that
of the corresponding solid preparation due to low stability.
5. Solution often provides suitable media for microbial growth and may,
therefore, require the incorporation of a preservative.
6. Liquid dosage forms e.g., vaccines may require special storage
conditions
7. The taste of a drug which is usually unpleasant is always more
prominent when in solution than in a solid form.
11. Classification of Solutions According to Vehicle
Based on the presence or absence of water, solutions
can be categorized into two main categories;
(a) Aqueous solutions
(b) Non-aqueous solutions
13. Classification of Solutions According to Physical
States of Solute and Solvent
The physical states of solute and solvent can be solid,
liquid or gas. Thus, depending upon the physical states
of the solute and solvent, there are nine types of
solution.
14. Solid-Solid Solution:
The physical state of both solute and solvent is solid.
Example: Metal alloy like bronze (common metal is actually an
alloy of tin and copper).
Solid-Liquid Solution:
The physical state of solute is solid and that of solvent is liquid.
Example: Solution of salt in water.
Solid-Gas Solution:
The physical state of solute is solid and that of solvent is gas.
Example: Sublimation of camphor in air.
Liquid-Solid Solution:
The physical state of solute is liquid and that of solvent is solid.
Example: Water into ice.
15. Liquid-Liquid Solution:
The physical state of both solute and solvent is liquid.
Example: Milk in water.
Liquid-Gas Solution:
The physical state of solute is liquid and that of solvent is gas.
Example: Water vapor in air.
Gas-Solid Solution:
The physical state of solute is gas and that of solvent is solid.
Example: Hydrogen adsorbed on platinum.
Gas-Liquid Solution:
The physical state of solute is gas and that of solvent is liquid.
Example: Carbonated drinks.
Gas-Gas Solution:
The physical state of both solute and solvent is gas.
Example: Mixture of various gases.
16. Classification of Solutions depending on the
dissolution of the solute in the solvent and
depending on the solvent used.
Depending on the dissolution of the solute in the solvent: There
are three types as follows:
• Saturated Solution: The solution in which no more solute can be dissolved
in the solvent is known as a saturated solution.
• Supersaturated Solution: The solution in which more solute is dissolved
than required to make a saturated solution is known as a supersaturated
solution.
• Unsaturated Solution: The solution in which more solute can be dissolved
in the solvent to make it a saturated solution is known as an unsaturated
solution.
17. Classification of Solutions depending on the dissolution
of the solute in the solvent and depending on the solvent used.
18. SELECTION OF SOLVENTS FOR LIQUID
PREPARATIONS
The selection of the proper solvent for a particular solute:
Solubility,
Clarity,
Low toxicity,
Viscosity,
Compatibility with other formulative ingredients,
Chemical inertness,
Palatability,
Odor, color,
Economy.
20. Formulation Components
Typical formulation components of oral solution dosage
forms include;
1. API.
2. Vehicle, which is usually aqueous but could also be vegetable oil.
3. Buffer for maintaining desired solution pH.
4. Sweetener, flavor, and color for improving palatability.
5. Taste masking agent, if required.
6. Antimicrobial preservative(s).
7. Antioxidant(s) or other stabilizer(s), if and when needed.
8. Surfactant(s), if and when needed.
21. Manufacturing Process
Typical manufacturing process for solution dosage forms involves simple mixing
of all ingredients to make a solution. However, several process variables need to
be carefully controlled to ensure a reproducible and high-quality manufacturing
process, such as sequence of addition of ingredients, process equipment and
parameters to control foaming and mixing dynamics, and temperature control.
Vehicle considerations include the selection of appropriate type and
concentrations of pH-controlling buffer, flavor(s), sweetener(s), color(s),
preservative(s), viscosity control agents in terms of their functionality,
compatibility with each other and the API, and stability in solution. Vehicles used
in oral solutions primarily include water, ethanol, glycerin, syrups, and various
blends of these ingredients. Aqueous-miscible cosol-vents used in smaller
concentrations include propylene glycol and polyethylene glycol.
Most of the vehicles used for oral solutions can be used in topical solu-tions. In
addition, topical solutions may also contain some amount of ace-tone,
isopropanol, propylene glycol, polyethylene glycols, many oils, and numerous
polymers.
22. Methods of Preparation of Solutions
(a) Simple Solution
(b) Solution by Chemical Reaction
(c) Solution by Extraction
(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
limited in water however, it dissolves in presence of KI due
the formation of more soluble polyiodides.
23. (b) Solution by Chemical Reaction
These solutions are prepared by reacting two or more
solutes with each other in a suitable solvent e.g. Calcium
carbonate and lactic acid used to prepare Calcium
lactate mixture.
(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.
24. 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.
Thus, 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.
25. Once reconstituted by the pharmacist, the solution
remains stable when stored in the refrigerator for the
labeled period, usually 7 to 14 days
This is a sufficient period for the patient to complete
the regimen usually prescribed.
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.
26. ORAL REHYDRATION SOLUTIONS
Rapid fluid loss associated with diarrhea can lead to dehydration
accompanied by depletion of sodium, potassium, and bicarbonate
ions.
Such condition can cause 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.
Oral rehydration solutions (ORS) are usually effective in treatment
of patients with mild volume depletion, 5% to 10% of body weight.
These are available as OTC are relatively inexpensive, and their use
has diminished the incidence of complications associated with
parenterally administered electrolyte solutions.
27. ORAL REHYDRATION SOLUTIONS
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.
Consequently, the goal is to replace lost fecal water with an oral
rehydration solution and use nutritional foods.
28. 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.
Typically, to circumvent hospitalization of the patient the night
before the procedure, patients were allowed to perform this regimen
at home.
However, while the results have been satisfactory, i.e., the bowel is
cleared for the procedure, poor compliance with and acceptance of
this regimen can cause problems during the procedure.
Furthermore, additive effects of malnutrition and poor oral intake
prior to the procedure can cause more patient problems.
29. ORAL COLONIC LAVAGE
SOLUTION
Consequently, 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. The PEG acts as an
osmotic agent in the gastrointestinal tract, and the balanced
electrolyte concentration results in virtually no net absorption or
secretion of ions.
Thus, a large volume of this solution can be administered without a
significant change in water or electrolyte balance.
30. ORAL COLONIC LAVAGE
SOLUTION
The formulation of this oral 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
31. ORAL COLONIC LAVAGE
SOLUTION
To date, this approach to bowel evacuation has been
associated with a low incidence of side effects (primarily
nausea, transient abdominal fullness, bloating, and
occasionally cramps and vomiting).
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.
No foods except clear liquids are permitted after this product
is administered and prior to the examination.
The product must be stored in the refrigerator after
reconstitution, and this aids somewhat in decreasing the salty
taste of the product.
