Istonic and Buffer Solutions
PHARMACEUTICAL CALCULATIONS
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Special Clinical Considerations of
Tonicity
Isotonic solutions are better tolerated by the patient than those at the extremes of hypo- and
hypertonicity
Most ophthalmic preparations are formulated to be isotonic, or approximately isotonic, to
duplicate ophthalmic tears or the comfort of the patient
Injections that are not isotonic should be administered slowly and in small quantities to minimize
tissue irritation, pain, and cell fluid imbalance.
Intravenous infusions, which are hypotonic or hypertonic, can have profound adverse effects
because they generally are administered in large volumes.
Even isotonic fluids, when in used intravenously in excessive volumes or at excessive rates, can
be deleterious due to an overload o fluids placed into the body’s circulatory system.
ISTONIC AND BUFFER SOLUTIONS
Physical/Chemical Considerations in
the Preparation of Isotonic Solutions
The calculations involved in preparing isotonic solutions may be made in terms of data
relating to the colligative properties of solutions. Theoretically, any one of these
properties may be used as a basis or determining tonicity.
Practically and most conveniently, a comparison of freezing points is used for this
purpose. It is generally accepted that −0.52°C is the freezing point of both blood serum
and lacrimal fluid.
ISTONIC AND BUFFER SOLUTIONS
Problems associated with NONELECTROLYTES
IIf the solute is a non-electrolyte, its solution contains only a molecules and osmotic
pressure varies with the concentration of the solute.
NOTE: By simple proportion, therefore, we can calculate the weight of any non
electrolyte that should be dissolved in each 1000 g of water if the solution is to be
isotonic with body fluids.
ISTONIC AND BUFFER SOLUTIONS
Problems associated with NONELECTROLYTES
BORIC ACID, OR EXAMPLE, HAS A MOLECULAR WEIGHT OF 61.8; THUS (IN THEORY), 61.8 G
IN 1000 G OF WATER SHOULD PRODUCE A FREEZING POINT OF −1.86°C. THEREFORE:
ISTONIC AND BUFFER SOLUTIONS
Problems associated with
ELECTROLYTES
IIf the solute is a electrolyte, its solution contains ions and the osmotic pressure varies
with both the concentration of the solute and its degree o dissociation. Thus, solutes that
dissociate present a greater number of particles in solution and exert a greater osmotic
pressure than do undissociated molecules.
ISTONIC AND BUFFER SOLUTIONS
Problems associated with
ELECTROLYTES
Simple isotonic solutions may then be calculated by using this formula:
ISTONIC AND BUFFER SOLUTIONS
Problems associated with
ELECTROLYTES
Example: If we assume that sodium chloride in weak solutions is about 80% dissociated,
then each 100 molecules yields 180 particles, or 1.8 times as many particles as are yielded
by 100 molecules of a non-electrolyte. This dissociation actor, commonly symbolized by
the letter i, must be included in the proportion when we seek to determine the strength
of an isotonic solution of sodium chloride (m.w. 58.5):
ISTONIC AND BUFFER SOLUTIONS
T he value of i for many medicinal salts has not been experimentally determined. Some
salts are exceptional (such as zinc sulfate, with only 40% dissociation and an i value
therefore of 1.4), but most medicinal salts approximate the dissociation of sodium
chloride in weak solutions. If the number of ions is known, we may use the following
values, lacking better information:
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
FORMULA USED FOR CALCULATING THE E EQUIVALENT OF SODIUM
CHLORIDE
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
Preparing Isotonic Solutions by
Volume Adjustment
As a convenience in compounding, a method of preparing isotonic solutions by volume adjustment may
be employed. The method, once described in the United States Pharmacopeia– National Formulary, is
based on the following:
By adding purified water to a 1-g quantity of a drug with a known E-value, a calculated volume of an
isotonic solution may be prepared. Then, by diluting this volume of solution with an isotonic vehicle, the
drug strength may be reduced while maintaining the solution’s isotonicity.
For example, 1 g of tetracaine hydrochloride (E=0.18) can prepare 20 mL of an isotonic solution,
calculated as follows:
ISTONIC AND BUFFER SOLUTIONS
Preparing Isotonic Solutions by
Volume Adjustment
The isotonic solution would contain 5% w/v tetracaine hydrochloride (1g/20
mL). If a solution of lesser strength is desired, a calculated quantity of an isotonic
vehicle, such as 0.9% sodium chloride, may be added. For example, if a 1% w/v
solution of tetracaine hydrochloride is desired, a total volume of 100 mL (1 g
tetracaine hydrochloride/100 mL) may be prepared by adding 80 mL of isotonic
vehicle to the 20 mL of the 5% w/v solution.
ISTONIC AND BUFFER SOLUTIONS
Preparing Isotonic Solutions by
Volume Adjustment
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
TRY THIS!!!!!
DETERMINE THE VOLUME OF PURIFIED
WATER AND 0.9% W/V SODIUM CHLORIDE
SOLUTION NEEDED TO PREPARE 20 ML OF A
1% W/V SOLUTION O HYDROMORPHONE
HYDROCHLORIDE (E = 0.22).
ISTONIC AND BUFFER SOLUTIONS
Use of Freezing Point Data in
Isotonicity Calculations
Freezing point data (DT ) can be used in isotonicity calculations when the agent has a tonicic
effect and does not penetrate the biologic membranes in question (e.g., red blood cells). As stated
previously, the freezing point of both blood and lacrimal fluid is −0.52°C. Thus, a pharmaceutical
solution that has a freezing point of −0.52°C is considered isotonic.
Representative data on freezing point depression by medicinal and pharmaceutical substances
are presented in Table 11.3. Although these data are for solution strengths of 1% , data or other
solution strengths and or many additional agents may be found in physical pharmacy textbooks
and in the literature.
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
SAMPLE PROBLEM:
HOW MANY MILLIGRAMS EACH OF SODIUM CHLORIDE AND LIDOCAINE
HYDROCHLORIDE ARE REQUIRED TO PREPARE 30 ML OF A 1% SOLUTION OF
LIDOCAINE HYDROCHLORIDE ISOTONIC WITH TEARS?
ISTONIC AND BUFFER SOLUTIONS
N OT E: SHOULD A PRESCRIPTION CALL FOR MORE THAN ONE
MEDICINAL AND/OR PHARMACEUTIC INGREDIENT, THE SUM OF
THE FREEZING POINTS IS SUBTRACTED FROM THE REQUIRED
VALUE IN DETERMINING THE ADDITIONAL LOWERING REQUIRED
BY THE AGENT USED TO PROVIDE ISOTONICITY.
ISTONIC AND BUFFER SOLUTIONS
Buffers and Buffer Solutions
The presence of certain substances or combinations of substances in aqueous solution imparts
to the system the ability to maintain a desired pH at a relatively constant level. Combinations of
substances are called buffers, and solutions of them are called buffer solutions.
Is a system, usually an aqueous solution, that possesses the property of resisting changes in
pH with the addition of small amounts of an acid or base.
In pharmacy, the most common buffer systems are used:
(i) the preparation of such dosage forms as injections and ophthalmic solutions, which are
placed directly into pH -sensitive body fluids
(ii) the manufacture of formulations in which the pH must be maintained at a relatively constant
level to ensure maximum product stability; and
(iii) pharmaceutical tests and assays requiring adjustment to or maintenance of a specific pH or
analytic purposes.
ISTONIC AND BUFFER SOLUTIONS
In the selection of a buffer system, due consideration must be given to the dissociation
constant o the weak acid or base to ensure maximum buffer capacity. Selected dissociation
constants, or Ka values, are given in Table 11.4.
ISTONIC AND BUFFER SOLUTIONS
ISTONIC AND BUFFER SOLUTIONS
Buffer Equation
THE EQUATION JUST DERIVED IS THE HENDERSON-HASSELBALCH EQUATION FOR WEAK ACIDS,
COMMONLY KNOWN AS THE BUFFER EQUATION.
SIMILARLY, THE DISSOCIATION CONSTANT, OR KB VALUE, OF A WEAK BASE IS GIVEN BY THE
EQUATION:
AND THE BUFFER EQUATION FOR WEAK BASES, WHICH IS DERIVED FROM THIS RELATIONSHIP, MAY
BE EXPRESSED AS:
ISTONIC AND BUFFER SOLUTIONS
pka Value of A Weak Acid With
Known Dissociation Constant
Calculating the pKa value of a weak acid, given its dissociation constant, Ka:
ISTONIC AND BUFFER SOLUTIONS
ph Value of A Salt/Acid Buffer System
ISTONIC AND BUFFER SOLUTIONS
Molar Ratio of Salt /Acid for a Buffer
System of Desired pH
ISTONIC AND BUFFER SOLUTIONS
Quantity of Components in a Buffer
Solution to Yield a Specific Volume
ISTONIC AND BUFFER SOLUTIONS
Change In pH With Addition of an
Acid or Base
ISTONIC AND BUFFER SOLUTIONS
Change In pH With Addition of an
Acid or Base
ISTONIC AND BUFFER SOLUTIONS
Electrolyte Solutions:
Milliequivalents, Millimoles,
and Milliosmoles
PHARMACEUTICAL CALCULATIONS
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Millimoles and Micromoles
A mole is the molecular weight of a substance in grams.
A millimole is one-thousandth of a mole and is, therefore, the molecular weight of a
substance in milligrams.
Similarly, a micromole is one-millionth of a mole, which is the molecular weight of a
substance in micrograms.
For example, the molecular weight of sodium chloride is 58.5 g/mol but can be
converted to milligrams and millimoles as follows:
ELECTROLYTE SOLUTIONS
Example Calculations of Millimoles
and Micromoles:
The following conversion can be used to convert milligrams to millimoles and vice
versa:
The following conversion can be used to convert micrograms to micromoles and vice
versa:
ELECTROLYTE SOLUTIONS
Example Calculations of Millimoles
and Micromoles:
(1) How many millimoles of monobasic sodium phosphate monohydrate (m.w. 138) are
present in 100 g of the substance?
(2) What is the weight, in milligrams, of 5 mmol of potassium phosphate dibasic? (m.w. 174)
ELECTROLYTE SOLUTIONS
Example Calculations of Millimoles
and Micromoles:
(3) Convert the trough plasma range of 0.5 mg/mL to 2 mg/mL for tobramycin
(m.w. = 467.52) to mmol/L.
Range = 1.07 to 4.28 mmol/L
ELECTROLYTE SOLUTIONS
Osmolarity
Osmotic pressure is proportional to the total number of particles in solution.
The unit used to measure osmotic concentration is the milliosmole (mOsmol).
1 mmol of NaCl represents 2 mOsmol (Na+ + Cl− ) of total particles, 1 mmol of
CaCl2 represents 3 mOsmol (Ca2+ + 2Cl− ) of total particles, and 1 mmol of
sodium citrate (Na3C6H 5O7) represents 4 mOsmol (3Na+ + C6H5O7− ) of total
particles.
According to the United States Pharmacopeia, the ideal osmolar concentration
may be calculated according to the equation:
ELECTROLYTE SOLUTIONS
Osmolarity
Osmotic pressure is proportional to the total number of particles in solution.
The unit used to measure osmotic concentration is the milliosmole (mOsmol).
1 mmol of NaCl represents 2 mOsmol (Na+ + Cl− ) of total particles, 1 mmol of
CaCl2 represents 3 mOsmol (Ca2+ + 2Cl− ) of total particles, and 1 mmol of
sodium citrate (Na3C6H 5O7) represents 4 mOsmol (3Na+ + C6H5O7− ) of total
particles.
According to the United States Pharmacopeia, the ideal osmolar concentration
may be calculated according to the equation:
ELECTROLYTE SOLUTIONS
Example Calculations of Milliosmoles:
ELECTROLYTE SOLUTIONS
(1) A solution contains 10% of anhydrous dextrose in water for injection. How many
milliosmoles per liter are represented by this concentration? Molecular weight of anhydrous
dextrose = 180 Dextrose does not dissociate, therefore the “number of species” = 1
ELECTROLYTE SOLUTIONS
(2) A solution contains 156 mg of K+ ions per 100 mL. How many milliosmoles are
represented in a liter of the solution? Molecular weight of K+ = 39 Number of species = 1
ELECTROLYTE SOLUTIONS
(4) Calcium chloride dihydrate injection is a 10% solution of CaCl2 · 2H 2O. How many
milliosmoles are present in a 10-mL vial? Assume complete dissociation. (m.w. 147; no. of
species = 3)
ELECTROLYTE SOLUTIONS
Clinical Considerations of Water
and Electrolyte Balance:
In clinical practice, fluid and electrolyte therapy are undertaken either to
provide maintenance requirements or to replace serious losses or deficits.
Na concentration = mEq/L
BUN = Blood Urea Nitrogen
Glucose concentration = mg/100 mL (mg/dL)
ELECTROLYTE SOLUTIONS
Example Calculation of Plasma
Osmolality:
(1) Estimate the plasma osmolality from the following data: sodium, 135 mEq/L;
blood urea nitrogen, 14 mg/dL; and glucose, 90 mg/dL.
ELECTROLYTE SOLUTIONS
Function of terrestrial
plant assemblages
PLANT SPECIES
E
14.7%
BEETLE SPECIES
A
23.5%
E
25.6%
A
B
5.1%
5.1% C
7.7%
PLANT SPECIES
A
2.8%
E
27.8%
BEETLE SPECIES
E
13.7%
B
13.9%
D
13.7%
D
32.4%
C
27.8%
B
14.7%
C
14.7%
D
56.4%
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
D
27.8%
A
45.2%
C
13.7%
B
13.7%
Function of
terrestrial
marine animal
assemblages
2,000
1,500
1,000
500
0
1
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
2
3
4
5
Field methods
to sample
marine animal
assemblages
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
METHOD 1
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
METHOD 2
METHOD 3
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Field methods to sample
terrestrial plant assemblages
STEP 1
STEP 2
STEP 3
STEP 4
STEP 5
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
Presentations are tools
that can be lectures,
speeches, reports,
assignments and more.
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
Outcomes
Presentations are communication tools that can be demonstrations, lectures,
speeches, reports, assignments and more. Presentations are communication tools
that can be demonstrations, lectures, and more. Presentations are communication
tools that can be demonstrations, lectures, speeches, reports, assignments and more.
Presentations are communication tools that can be demonstrations, lectures, and
more. Presentations are communication tools that can be demonstrations, lectures,
speeches, reports, assignments and more.
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
Analysis
Presentations are tools that can be demonstrations, lectures,
speeches, reports, assignments and more. Presentations are
communication tools that can be demonstrations, lectures, and
more. Presentations are communication tools that can be
demonstrations, lectures, speeches, reports, assignments and
more. Presentations are communication tools that can be
demonstrations, lectures, and more. Presentations are
communication tools that can be demonstrations, lectures,
speeches, reports, assignments and more.
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A
Presentations are communication tools that can be
demonstrations, lectures, and more. Presentations are
communication tools that can be demonstrations, lectures,
speeches, reports, assignments and more. Presentations are
communication tools that can be demonstrations, lectures, and
more. Presentations are communication tools that can be
demonstrations, lectures, speeches, reports, assignments and
more.
Thank you
NADIA WILLIAMS | UNIVERSITY OF VICTORIA | SCIENCE: LIFE SCIENCES | #29782A