2DPH Group 3

Part 1 by Hannah Co
h liquid preparations that contain one or
more chemical substances dissolved in
suitable solvent or mixture of mutually
miscible solvents.
h According to use
h According to composition
Solute Solvent
Solid Solid
Solid Liquid
Solid Gas
Liquid Solid
Liquid Liquid
Liquid Gas
Gas Solid
Gas Liquid
Gas Gas
Solutions may be prepared from any combination of solid,
liquid, and gas. Possible combinations are:
h Attractive forces between atoms lead to the
formation of molecules and ions.
h There are two kinds of forces that occur in
chemical compounds: intramolecular and
intermolecular forces.
h The force between atoms within a molecule
h The force between molecules is a physical or
intermolecular force.
h Responsible for the physical state(solid, liquid, gas)
of substance under given conditions such as
pressure and temperature.
h The hydrogen bond is
really a special case of
dipole forces.
h A hydrogen bond is the
attractive force between
the hydrogen attached to
an electronegative atom of
one molecule and an
electronegative atom of a
different molecule.
h Usually the electronegative
atom is oxygen, nitrogen,
or fluorine, which has a
partial negative charge.
h When molecules interact, attractive and repulsive forces
are in effect. The attractive forces cause the molecules to
cohere, whereas the repulsive forces prevent molecular
interpenetration and destruction. When attractive and
repulsive forces are equal, the potential energy between
the two molecules is minimal and the system is most
stable.
h solute-solute forces must be broken
h solvent-solvent forces must be broken
h attraction between solute and solvent, forming
solute-solvent interaction
h The extent to which the solute dissolves in
the solvent.
h The extend of solubility of different
substances varies from almost
imperceptible amounts to large quantities.
h The solubility of a pure chemical substance
at a given temperature and pressure is
constant.
h Solubility can be expressed by many ways.
For example, the solubility of sodium
chloride in water at 25 may be stateu as
g of souium chloiiue uissolves in
mL of watei0SP
g of souium chloiiue uissolves in
mL of watei
Descriptive Term
Parts of solvent required for 1
part of solute
Very soluble <1
Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10000
Practically insoluble or insoluble >10000
h Depends on particle size of substance and extent
of agitation.
h The finer the powder, the greater the surface
area, which comes in contact with the solvent,
and the more rapid the dissolving process.
h The greater the agitation, the more unsaturated
solvent passes over the drug and the faster the
formation of solution
h Maximum concentration to which a solution may
be prepared with that agent and that solvent.
h Maximum possible concentration varies greatly
and depends on chemical constitution of solute.
h Temperature
h Physical and Chemical Properties of solute
and solvent
h pH of the solution
h State of subdivision of solute
h Physical agitation applied to the solution as
it dissolves
If Heat is Temperature Solubility
Positive,
absorbed
increase increase
Negative,
released
increase decrease
Not
absorbed
or
released
Increase/
decrease
Not
affected
h The solubility of a
nonelectrolye is
decreased or increased
generally by the addition
of an electrolyte.
h When the solubility of a
nonelectrolyte is
decreased, the effect is
referred as salting-out; if
it is increased, the effect
is referred as salting-in.
h Increasing the pH shifts the equilibrium from
right to left, decreasing the solubility.
h Decreasing the pH shifts the equilibrium from
left to right, increasing the solubility
h Many of the important
organic medicinal
agents are either weak
acid or bases, and their
solubility depends to a
large measure of the
pH of the solvent.
h These drugs react
either with strong
acids or strong bases
to form water soluble
salts.
ATROPINE SULFATE: Corresponding
salt of atropine formed by the reaction
of atropine and sulfuric acid.
h Based on molecular structure and functional
groups(more applicable to organic
compounds)
h General patterns of solubility that applies to
inorganic compounds
h like dissolves like
principle
h Organic compounds are
more soluble in organic
solvents than water.
h Organic compounds may
be somewhat soluble if
they contain polar
groups capable of
forming hydrogen bonds
with water.
Benzene
1 g in 1430 mL of
water
Benzoic Acid
1 g in 275 mL of water
h An increase in
molecular weight of an
organic compound
without a change in
polarity reduces
solubility in water.
h Some general patterns include:
Most salts of monovalent cations are water soluble
whereas divalent cations usually form water-soluble
compounds with nitrate, acetate, and chloride.
h Some didnt have solubility characteristics.
Magnesium sulfate(Epsom salt) is soluble
Mercurous chloride is insoluble and used as cathartic, while
mercuric chloride is soluble in water and is a deadly poison if
taken internally.
h The selection is based on such additional
characteristics as clarity, low toxicity,
viscosity, compatibility with other
formulative ingredients, chemical inertness,
palatability, odor, color, and economy.
h In most instances, water is the preferred
solvent.
h Employed to augment
the solvent action of
water or to contribute
to a products chemical
or physical stability.
h Alcohol, glycerin and
propylene glycol are
some examples
h Solvents that are not to
be taken internally but
useful reagent solvents
in organic chemistry
and preparatory stages
of drug development,
as in the extraction or
removal of active
constituents in
medicinal plants
h Acetone, ethyl oxide,
isopropyl alcohol
One of the extracts from dried
whole leaf of Gingko Biloba L..
Extracts have been used for
symptomatic treatment of mild to
moderate cerebrovascular
insufficiency
h Alcohol, USP; Ethyl Alcohol, Ethanol
h Diluted Alcohol NF
h Rubbing Alcohol
h Glycerin USP(Glycerol)
h Isopropyl rubbing alcohol
h Propylene Glycol
h Purified Water, USP
h Next to water in being the most useful solvent
h Alcohol USP is 94.9% to 96.0% v/v ethyl
alcohol(ethanol) and is commonly used as a
single auxiliary solvent and with other
auxiliary solvents, e.g. glycerol, to reduce
amount of water required.
h Dehydrated Alcohol USP
contains n.l.t. 99.5%
ethanol by volume and is
used when essentially
water-free alcohol is
desired.
h FDA restrict
manufacturers in the use
alcohol and include
appropriate warnings in
labeling OTC
medications.
Age
Alcohol
content limit
< 6 years 0.5%
6-12 years 5%
>12 years 10%
h Prepared by mixing equal volumes of
alcohol, USP, and purified water, USP.
h The final volume is not equal to the sum of
the two components because liquids
contract upon mixing.
Final volume is 3% less that what is expected
h Contains 70% ethyl alcohol by volume ,
remainder consisting of water, denaturants,
with or without color additives and perfume
oils, and stabilizers.
h Denaturing is a process of adding other
compounds to the ethanol to render it unfit
for consumption. Denaturants such as
sucrose octaacetate or denatonium
benzoate are such examples that have bitter
taste.
h Clear syrupy liquid
with a sweet taste.
h Miscible in water and
alcohol
h Used as an auxiliary
solvent in conjunction
with water or alcohol.
h 70% by volume isopropyl alcohol,
remainder consisting of water with or
without color additioes, stabilizers and
perfume oils.
h 91% isopropyl alcohol solution are
employed by diabetic patients in preparing
needles and syringes for hypodermic
injections of insulin and for disinfecting the
skin.
h Viscous liquid,
miscible with water
and alcohol.
h Used as a replacement
for glycerin.
h Useful in
pharmaceutical
preparations as a
auxiliary solvent.
h Naturally occurring water is impure and
contains varying amounts of dissolved
inorganic salts, along with dissolved and
undissolved organic matter and
microorganisms.
h Water purified by drinking contains less
than 0.1 % of total solids.
h According to U.S. Public Health Service
regulations, acceptable drinking water
should be clear, colorless, odorless, and
neutral or only slightly acidic or alkaline.
h Ordinary drinking water from tap is not
acceptable for the manufacture of most
aqueous pharmaceutical preparations
because there might be chemical
incompatibilities.
h Purified Water, USP, has fewer solid
impurities than ordinary drinking water.
When evaporated to dryness, it must not
yield more than 0.001% residue(1 mg of
solids per 100 mL of water).
h It is used in preparation of aqueous dosage
forms except those intended for parenteral
administration.
h Distillation method
h Ion exchange method
h Reverse Osmosis
h 0.5 to 100 gallons of
distillate per hour.
h Involves evaporation
and condensation
h First portion of
aqueous distillate and
last portion must be
discarded.
h More efficient
h Lesser cost. Used in
pharmacies and in
small laboratories
h Composed of ion
exchange equipment
h Cations, acid exchangers, exchange of cations
in solution, with H-ions from the resin
h Anions, base exchange resins, which permit the
removal of anions
h Cross-flow (or
tangential flow)
membrane filtration
h Permeate-fresh water
h Concentrate-
contaminated water
h Methods of expressing strengths of
pharmaceutical preparations
h Methods to hasten dissolution
Expression
Abbreviated
Expression
Meaning
Percent weight in volume % w/v
Grams of constituent in
100 mL of preparation
Percent volume in volume %v/v
Milliliters of constituent in
100 mL of preparation
Percent weight in weight %w/w
Grams of constituent in
100 g of preparation
Ratio strength; weight in
volume
-:- w/v
Grams of constituent in
stated milliliters of
preparation
Ratio strength: volume in
volume
-:- v/v
Milliliters of constituent in
milliliters of preparation
Ratio strength: weight in
weight
-:- w/w
Grams of constituent in
stated number of grams of
preparation
h Applying heat
h Reducing the particle size of solute
h Using solubilizing agent
h Subjecting ingredients to vigorous agitation
h Contain
Flavorants and colorants (to make attractive
and palatable)
Stabilizers (to maintain physical and chemical
stability)
Preservatives(to prevent microbial growth)
h Esters of p-hydroxybenzoic acid (methyl-, ethyl-,
propyl-, butylparabens)
h A number of medicinal
agents such as
antibiotics, penicillin V,
have insufficient
stability to meet
extended-shell life
periods.
h This is why
commercial
manufacturers provide
them in dry powder or
granule form.
h Once reconstituted, solution remains stable
for 7 to 14 days, depending on formulation
h Examples are:
Cloxacillin Sodium for oral solution(Teva), anti-
infective antibiotic
Penicillin V Potassium for Oral Solution, USP
(Veetids,Geneva), an anti-infective antibiotic
Divided into:
h Oral Rehydation Solutions
h Oral Colonic Lavage Solution
h Magnesium Citrate Oral solution
h Sodium citrate and citric acid oral solution
h In the normal healthy intestine, there is a
continuous exchange of water through the
intestinal wall - up to 20 liters of water is
secreted and very nearly as much is
reabsorbed every 24 hours - this mechanism
allows the absorption into the bloodstream of
soluble metabolites from digested food.
h During diarrhea, the
small intestine
secretes far more than
the normal amount of
fluid and electrolytes,
and this simply
exceeds the ability of
large intestine to
absorb it.
h Effective in treatment
of patients with mild
volume depletion, 5%
to 10% of body weight.
h Good for 24 hours
Ingredients Amount
Na ion 45 mEq
Potassium ion 20 mEq
Chlorine ion 35 mEq
Citrate 30 mEq
Dextrose 25 g
A liter of Oral Rehydration Solution contains:
h Simply giving a saline
solution (water plus Na
+
)
by mouth has no beneficial
effect because the normal
mechanism by which Na
+
is absorbed by the healthy
intestinal wall is impaired
in the diarrheal state
h If glucose (also called
dextrose) is added to a
saline solution a new
mechanism comes into
play.
h Pedialyte Solution (Ross)
h Rehydralyte Solution (Ross)
h Infalyte Oral Solutions (Bristol-Myers Squib)
Contains electrolytes in syrup of rice solids
Produce lower osmotic effect and lessen stool
output
h Used for preparations of
the bowel for
procedures such as
colonoscopy.
h PEG acts as osmotic
agent.
h Balance electrolyte
concentration results in
virtually no net
absorption and
secretion of ions.
In 4800 mL of water
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
h Colorless to slightly yellow clear effervescent
liquid
h Sweet, acidulous taste
h Lemon flavor
h Citrate of magnesia
h Used as saline cathartic
h 1.55 to 1.9 g in 100mL
h Equation 13.1 and 13.2
h Solution provides excellent medium for
growth of molds, and any mold spores
should be killed for preparation to be stable.
h Tendency to deposit a solid crystalline form
upon standing due to formation of almost
insoluble normal magnesium citrate
h Formula calls for
preparation of 350 mL
of magnesium citrate
with the use of 5 g
official magnesium
carbonate which
corresponds to 6.0 to
6.47 g of magnesium
oxide.
h Official solution contains sodium citrate
100mg and citric acid 67 mg in each mL of
aqueous solution.
h Systemic alkalinizer
h Solution is administered 10 to 30 mL as
frequently as four times daily
h Concentrated aqueous preparations of sugar or
sugar substitute with or without flavoring
agents and medicinal substances
h Without medicated substances(nonmedicated or
flavored vehicles).table 13.6
h Medicated syrups. Table 13.7
h Syrups provide pleasant means of administering
a liquid form of a disagreeable tasting drug.
h Water soluble drug that is stable in aqueous
preparation may be added to syrups.
h Syrups contain the following components in
addition to the purified water present:
Sugar, usually sucrose
Antimicrobial preservatives
Flavorants
Colorants