Pharmaceutical solutions

Introduction
• Liquid dosage forms is one of the oldest dosage
forms used in treatment.
• Liquid dosage forms have Rapid & High
absorption of soluble medicinal products .
• Particular use for individuals having difficulty in
swallowing (e.g.: Pediatric, Geriatric, Intensive
care & Psychiatric) Patients.
• Solutions are homogeneous liquid preparations
containing one or more completely dissolved
components (One-phase system).
 Solutions: Definition
• Solution is 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 the solute or dissolved substance are
dispersed.
• Pharmaceutical solutions defined as liquid preparations
in which the therapeutic agent and the various
excipients are dissolved in the chosen solvent system.
• Pharmaceutical solutions are homogeneous, i.e. the
therapeutic agent(s) and excipients are dissolved in the
vehiclee.
 Advantages of pharmaceutical solutions
The drug immediately available for absorption. By providing -1
drug in a solution, high dissolution may results → quicker
.absorption
Flexible dosing is possible. The active ingredient within sol. -2
.present in a certain Conc. per unit volume
Solutions are designed for any route of absorption: the oral -3
route of administration , via Parenteral preparations
(injections), enemas for rectal use, Topical (for use on skin)
.& ophthalmic preparations are all sols
No need to shake the container. Unlike suspensions as the -4
.active ingredient is dissolved within the vehicle
Facilitate swallowing in difficult cases (e.g. infants or the -5
. elderly). It is more easier for patients to take solution
 Disadvantages of solutions
Drug stability is reduced in Sol by hydrolysis or oxidation. For -1
this reason, Sol. is commonly has a shorter expiry date than
.equivalent solid dosage forms
.It is difficult to mask unpleasant tastes -2
A major disadvantage ; they are much larger & more bulky, -3
difficult to transport. Liquids packed in glass bottles are
obviously prone to breakage and cause loss of the
.preparation
Some drugs are poorly soluble so it is necessary to alter -4
.vehicle or drug form in order to formulate a convenient prep
A measuring device is needed for admin. so need to be -5
supplied to the patient to be able to measure an accurate
. dose
 Classification of pharmaceutical solutions

: According to the vehicle

:Aqueous solutions -1
Solutions that contain water as the solvent. For example,
sugar in water, carbon dioxide in water, etc
: Non-aqueous solutions -2
Solutions that contain a solvent other than water. Ether,
benzene, petrol, carbon tetrachloride etc., are some
common solvents. For
example, sulphur in carbon disulphide, naphthalene in
benzene, etc
 Classification of pharmaceutical
solutions
: According to their intended use
Oral solutions -1
2- Otic solutions
3-Ophthalmic solutions
4- Topical solutions
5-Parenteral preparations Solutions
6- Rectal solutions 7-
Vaginal solutions 8-
Nasal solutions 9-
inhalation
 Formulation of solutions
Drug(s) + Range of excipients include: 1- *
The vehicle ( Solvent): Purified Water - Oil 2-Co-
solvents, e.g. propylene glycol , glycerol, ethanol
3- Surface-active
agents : To enhance solubility
of the therapeutic sub. in vehicle.
4- Preservatives : Against microbial
contamination 5-Sweetening agents, e.g. glucose,
saccharin, aspartame
6- Viscosity modifiers: e.g. cellulose derivatives,
7-Antioxidants, e.g. butylated hydroxytoluene 8-
Coloring & Flavoring agents (oral only) 9-
Buffering agents , to regulate the pH of the formulation
 Methods of Preparation
Simple Solution : -1
prepared by dissolving the solute in the solvent
Examples: Calcium hydroxide solution USP (lime water),
Sodium Phosphate solution and Strong Iodine solution
USP (lugol’s)
2- Solution by Chemical reaction :
prepared by reacting two or more solutes with each other
in a suitable solvent.
Examples:
Aluminum subacetate :
prepared by reacting aluminum sulfate sol. with calcium
.carbonate and acetic acid forming magma
 
 Methods of preparation
Magnesium Citrate :
prepared by reacting official magnesium carbonate with
citric acid, flavoring and sweetening agents, filtering talc
and carbonating it by potassium or sodium bicarbonate.
Use: Saline cathartic
Sodium Citrate and Citric acid oral solution :
contains 100mg sodium citrate and 67 mg citric acid in
each ml aqueous solution.
Use: Systemic alkalinizer
Solution by Extraction : -3
vegetables or animal origin are often extracted with
suitable solvent.
Preparation of this type may be classified as solutions
 Excipients used in solutions
• Excipients are pharmacologlly inert compounds
that are included in the pharmaceutical
formulations which help in :
1-To facilitate the administration of the dosage
form, e.g. pourability and palatability,
2-To protect the formulation from issues
regarding physical and chemical stability.
3-To enhance the solubility of the therapeutic
agent.
• Pharmaceutical sols. contain a wide range of
excipients. :
1- Vehicles (Solvents):

• Vehicle is the medium containing the ingredients of a drug.

• In solutions, the vehicle is the solvent.
• The choice of a vehicle depends on: a)
The intended use of the preparation b)
The nature & physicochemical properties of active Ingredients
• Water as a vehicle :
-Water is the most vehicle used in solutions.
-Water used as the primary solvent because of: 1-
Widely available 2-
Relatively inexpensive 3-
Palatable 4-
Non-toxic for oral use 5-
Non-irritant for external use.
Water is also a good solvent for many ionizable-
drugs
-Salts of organic compounds are more soluble in
water
-Water is the preferred solvent for solutions to be
taken orally, used ophthalmically, or injected
• Type of water :
1- Potable water :
Drinking water, should be palatable & safe for
drinking, Its chemical composition may include
mineral impurities which could react with drugs.
2 - Purified water USP:
Obtained from potable water by distillation, ion
exchange treatment or reverse osmosis.
Distilled water is purified water prepared by
distillation. 
Purified water are used in oral or external
preparations and not intended to be sterile
3- Water for injections:
Pyrogen-free distilled water, sterilized immediately
after collection and used for Parenteral
preparations.
 
4 -Sterile water for injection:
It is water for injection sterilized & packaged
in a suitable single dose container of glass type of
not larger than 1000ml size.
5-Chloroform water :
Used as antimicrobial preservative and also
adds sweetness to preparations.
6- Aromatic water :
Saturated solution of volatile oils in water and
are used to provide a pleasant flavor or aroma,
e.g. Peppermint Water, USP.
Used as a vehicle in oral sol
2- Co-solvents :
• Employed to increase the solubility of therapeutic agent within
the formulation.
• Glycerol (also termed glycerin) Glycerol is a clear odorless,
viscous liquid, with a sweet taste , and miscible with both
water and alcohol. -Its co-solvency
properties due to the presence of three hydroxyl gps(oH).

• Alcohol USP (CH3CH2OH) Contain

between 94.9 and 96.0% v/v ethyl alcohol(ethanol).
Commonly used as a co-solvent, both as a
single and with other co-solvents, e.g. glycerol.
The known pharmacological & toxicological effects of alcohol
have compromised its use in pharmaceutical preparations.
• Propylene Glycol USP .
3- Miscellaneous agents:
• Used to enhance solubility of therapeutic agents.
• These include the use of surface-active agents and
Complexation . a-
Surface-active agents(surfacants) : These
are chemicals that possess both hydrophilic (water-
liking) and hydrophobic (water-disliking) regions.
B- Complexation :
Complexation refers to the
interaction of a poorly soluble therapeutic agent with an
organic molecule. e.g. surface-active agents, hydrophilic
polymers to generate a soluble intermolecular complex.
4-Buffers:
• Buffers employed within pharmaceutical sols. to
control pH of the formulated product and, to
optimize the physicochemical performance of the
product.
• Typically pH control is performed to maintain the
solubility of therapeutic agent of the product.
• Examples of buffer salts used in pharmaceutical
solutions include:
-Acetates (acetic acid and sodium acetate): about 1–2%
- Citrates (citric acid and sodium citrate): about 1–5%
-Phosphates (sodium phosphate and disodium phosphate)
about 0.8–2%.
5- Sweetening Agents :
• Sweetening agents are employed in liquid
formulations designed for oral administration
specifically to increase the palatability of the
therapeutic agent.
• The main sweetening agents employed in oral
preparations are sucrose, liquid glucose, glycerol,
sorbitol, saccharin sodium and aspartame
6- Viscosity -enhancing Agents :
• The administration of oral solutions to patients by
using a syringe, a small-metered cup or a traditional
5-ml spoon.
• The viscosity of formulation must be controlled to
ensure the accurate measurement of the dispensed
volume.
• Increasing the viscosity of → increase the palatability
• The viscosity of pharmaceutical solutions increased
by the addition of non-ionic or ionic hydrophilic
polymers 1-
Non-ionic (neutral)polymers: cellulose derivatives
e.g.: methylcellulose ,hydroxyethylcellulose
2- Ionic polymers: sodium carboxymethylcellulose,
sodium alginate
 
7- Antioxidants :
• Antioxidants included in pharm. Sol. to enhance the
stability of drugs that susceptible to chemical
degradation by oxidation.
• Antioxidants are compounds that inhibit free radical-
induced drug decomposition.
• Both water-soluble & water-insoluble antioxidants
areavailable.  
• Antioxidants for aqueous formulations eg; Sodium
sulphite, sod. metabisulphite, sod. formaldehyde
sulphoxylate and ascorbic acid.
• Antioxidants used in oil-based solutions e.g; butylated
hydroxytoluene (BHT), butylated hydroxyanisole (BHA)
and propyl gallate
8-Preservatives :
• Preservatives are included in pharmaceutical solutions to reduce or
prevent the microbial growth of the formulation.
• Ideally, preservatives should exhibit the following properties
1-possess a broad spectrum of
antimicrobial activity includes Gram-positive,Gram-negative
bacteria & fungi. 2-be chemically and physically stable
over the shelf-life of the product.
3-have low toxicity.

• Examples: benzoic
acid and salts (0.1–0.3%). sorbic acid and
its salts (0.05–0.2%). Alkyl esters of
parahydroxybenzoic acid (0.001-0.2%).
• A combination of two preservatives employed in solutions to
enhance the antimicrobial spectrum. Methyl & propyl
parahydroxybenzoates (in a ratio 9:1)
9-Flavours:
• The vast majority of drugs in solution are unpalatable, so the
addition of flavors to mask the taste of drug substance is important .
• Flavours added to make a medicine more acceptable to take

• Four basic taste sensations are salty, sweet, bitter and sour
a-Flavours used to mask a
salty taste include: butterscotch , apricot , peach , vanilla,
wintergreen mint. b- Flavours used to mask a bitter taste include:
cherry , mint , anise
c- Flavours used to mask a sweet taste include: vanilla,
fruit and berry d- Flavours used
to mask a sour taste include: citrus flavours. ,
raspberry.
• A combination of flavours is used to achieve the optimal taste-
masking property.
10 Colourants:
• Colours are pharmaceutical ingredients that
impart the preferred colour to the formulation.
• When used in combination with flavours, the
selected colour should ‘match’ the flavour of the
formulation,
e.g. green with mint-flavoured solutions, red for
strawberry-flavoured formulations.
• Although colours is not a prerequisite for all
pharmaceutical sol., certain categories of
solution (e.g. mouthwashes/gargles) are
normally coloured
 Pharmaceutical solutions for oral
administration
There are three principal types of solution
:formulations that are administered orally
Oral solutions -1
Oral syrups -2
.Oral elixirs -3
In addition, other solution formulations are
employed for a local effect, e.g.
.mouthwashes/gargles and enemas