2.a drug must be in solution before it can be absorbed. a drug administerred in the form of a solution is immediately available for administration.
3.a solution is a homogenous system; the drug will be uniformly distributed throughout the prepartion.
4. some drugs can irritate and damage the gastric mucosa particularly if localized in one area as often occurs after ingestion of a solid dosage form. irritation is reduced by administration of a solution of a drug, because of the immediate dilution by the gastric contents.
disadvantages of a solution
1.bulky and inconvenient to transport and store
2.the stability of ingredients in aqueous solution is often poorer than if they were formulated as a tablet or capsule.
3.solutions provide suitable media for the growth of microorganisms
4.accuret dosage usually depends on the abiltity of patient to use a 5 ml spoon or a volumatric dropper.
5.the taste of a drug,which is usually unpleasant is always more pronounced when in solution that when in a solid form.
homogenous mixture that are prepared by dissolving a solid, liquid or gas in an aqueous medium (vehicle=water)
lack of toxicity
lack of pharmacological activity
ability to dissolve a wide range of materials
not permitted to use tap water for the dispensing of pharmaceutical dosage forms due to possibel bacterial contamination and the presence of dissolved salts that destroy the active ingredients or enhance their decomposition
freshly boild and cooled water
boiling is seldom used to destroy vegetative bacteria. however; on storage for long time spores may yield microorganism.
must be used for most pharmaceutical operations and in all the tests
such water is prepared by suitable process: distillatiion, ion-exchange, or reverse osmosis.
ultraviolet energy,heat or filtration can be used to remove or kill the microorganisms present in the water.
contains no added substances
not for parenteral administration
water for injection
must be used for the formulationof parenteral solutions
obtained by sterilizing pyrogen-free distilled water.
contains no added substances.
bacteriostatic water for injection
prepared from sterilized water for injection
contains one or more antimicrobial agents
it is used to dilute or dissolve particular medicinal substance to be used for as parenteral solutions.
oldest method of water purification
water is first heated to boling
water vapor rises to condenser where cooling water lowers the temperature so the vapor is condensed, collected and stored.
most contaminats remain behind in the liquid phase vessel.
advantages of DW
remove a broad range of contaminants
disadvantage of DW
some contaminants can be carried into the condensate
requires careful maintenance to ensure purity
consumes large amount of energy and water.
ion exchange method
ion-exchange equipment passes water through a column of cation and anion exchanger consisting of water-insoluble synthetic resins types
resin made of styrine and divinylbenzen containing sulfonic acid groups which exchange a hydrogen inon for cation( na++,Ca++, AL++++)
resin made of styrine and containing quaternary ammonium groups which exchange a hydroxyl ion for any anions ( Cl-, Co3-)
advantages of ion-exchange method over distillation method
no heat requirement
ease of operation
disadvantages of ion-exchange method over distillation method
does not effectively removes particles,pyrogens or bacteria
it is a process known as cross-flow membrane filtration
it works by using pressure in excess of the osmotic pressureto force a solution through a membrane, retaining the solute on one side and allowing the pure solvent to pass to the other side
this is the reverse of the normal osmosis process which is the natural movement of solvent from an area of low solute concentration, though a semi-permiable membrane, to an area of high solute concentration when no external pressure is applied.
advantages of RO
effectively removes all types of contaminants to some extent (particles,pyrogens,mo, dissolved salts)
disadvantages of RO
flow rates are usually limited
clear, saturated aqueous solutions of volatile oils or other aromatic or volatile substances
they are used principally as flavored or perfumed vehicles
stability issue :
1. oils or volatile substance are not stable, easily oxidized
2.store in light container,cool place
3.protect from light
4.protect from heat
5.discard if cloudy or color changes
the use of alternative solvents
if it is not possible to ensure complete dissolving of the ingredients at all storage temperatures.
if the drug is unstable in aqueous systems
the use of non aqueous systmes may also have other advantages; IM injection of solution of durgs in oils is often used for depot therapy
solvennt should be: non toxic, non irritant, inexpensive,stable and compatible with other ingredients.
solvents such as aceton,benszene and petroleum ether are not used ofr internal products.
internal products may contain ethanol,glycerol,sorbitol,PG and certain oils
for parentral poducts the choice is very limited
these are non-volatile oils consisting mainly of fatty acid esters of glycerol
almond oil, coconut oil
some fixed oils are sufficiently tastelss and odorless to be suitable for oral use as solvents for such materials as vitamin A and D
oils tend to be unpleasent to use externally unless presented as an emulsion
ethyl alcohol (usp),ethanol C2H5OH
it is the most widely used solvent next to water in pharmacy(primerly solvent for many organic compounds)
it forms hydroalcoholic mixture with water that dissolves both water soluble and alcohol solube substances. this property is very useful in extraction of active constitents from crude drugs
alcohol USP: 94.9%, to 96.0% v/v ethanol
dehydrated alcohol USP: contains no less than 99.5% v/v ehtanol
alcohol is preferred because of its miscibillity with water and its ability to dissolve many water insoluble drugs, flavorings and preservatives.
commonly used as a co-solvent, both as a single co-solvent and with other cosolvents( to reduce amount of alcohol used)
for external application: rapid evaporization after application to the skin imparts a cooling effect.
it has an antimicrobial property( at a concentration = or greater than 15 %)
it is used via oral or parenteral routes only at low concentration
alcohols containing two hydroxyl groups per molecule are known as glycols
due to their toxicity, they are rarely used internally
propylene glycol is often used in conjunction with water as a cosolvent
propylene glycol USP is an odorless, colorless, viscous liquid
poly(ethylene) glycol PEG
is a polymer composed of repeating units of the monomer ethylene oxide
the physical state of the polymer is dependent on the number of repeat units (n) and hence on the molecular weight
lower-molecular weight grades( PEG 200, PEG400) are preferred as co-solvents with water or alcohol in pharmaceutical solutions, HOCH2(CH2CH2O)nCH2OH
an alcohol possessing three hydroxyl groups per molecule
odorless,sweet liquid that is miscible with water
it is used as co-solvent with water and alcohol
comparable to alcohol, it is viscous, so solutes are slowly soluble in it unless it is rendered less viscous by heating
it has a preservative property
unsed in many internal preparations
this is a highly polar compound and is thought to aid the penetration of drugs through the skin
this material is widely used for the extraction of crude drugs
the oily nature of this material makes it unpleasant to use extrenally, although it is often used as a solvent for the topical application of drugs in emulsion formulations
use of co-solvents
co-solvents are liquid components that are incorporated into a formulation to enhance the solubility of poorly soluble drugs to the required level
commonly employed co-solvents include glycerol proylene glycole ethanol and polyethylene glycol
in practic the pharmaceutical scientists should measure the solubility of the chosen therapeutic agent in a series of mixed solvents to determine the most suitable solvent system for the given purpose
the final choice of the co-solvent system for a particular formulation involves consideration of the solubility of therapeutic agent in the vehicle, the toxicity of the vehicle and the cost of the formulation
idealy suitable co-solvent blend should possess values of dielectric constant between 25-80 e.g water /ethanol