‫מבוא לרוקחות‬

Introduction to Pharmacy
Course # 64301
Tawfeeq Shekh-Ahmad, PhD
School of Pharmacy
Faculty of Medicine
Hebrew University of Jerusalem

1
Dose Definitions
• The dose of a drug is the quantitative amount administered or taken by a patient
for the intended medicinal effect.
• The dose may be expressed as a single dose, the amount taken at one time; a
daily dose; or a total dose, the amount taken during the course of therapy.
• A daily dose may be subdivided and taken in divided doses, two or more times
per day depending on the characteristics of the drug and the illness.
• The schedule of dosing (e.g., four times per day for 10 days) is referred to as the
dosage regimen.

2
Dose Measurement
11
• 1 teaspoonful (tsp.) = 5 mL
• 1 tablespoonful (tbsp.) =15 mL I
• Drop (abbreviated gtt) – NOT a definite quantity
1 mL of water = 1 gram or 1000 mg ÷ 50 mg [ave.]/drop = 20 drops).

3
Dose Measurement
• How many milligrams each of hydrocodone bitartrate and guaifenesin will be contained in each
dose of the following prescription?

1 teaspoonful = 5 mL foodfino
120 ÷ 5 = 24 doses
0.12 g ÷ 24 = 0.005 g = 5 mg hydrocodone bitartrate
2.4 g ÷ 24 = 0.1 g = 100 mg guaifenesin

4
 017760 101019 14
Calculation of Doses: Patient Parameters
• The drug’s usual dosage range is the range of dosage determined to be safe and effective in that
same population group
• For certain drugs and for certain patients, drug dosage is determined on the basis of specific
patient parameters: age, weight, body surface area
• Patients requiring individualized dosage: neonates and other pediatric patients, elderly patients
with diminished biologic functions, individuals of all age groups with compromised liver and/or
kidney function, critically ill patients, patients being treated with highly toxic chemotherapeutic
agents

5
Pediatric Patients
• neonate (newborn), from birth to 1 month
• infant, 1 month to 1 year
• early childhood, 1-5 years
• late childhood, 6 - 12 years
• adolescence, 13 - 17 years
• A neonate is considered premature if born at less than 37 weeks’ gestation

6
 Calculations of Dose
Based on Age

iiii
7
Calculations of Dose
Based on Body Weight

Based on body surface area (BSA)

8
 1170101 1114510 1710117
Isotonic and Buffer Solutions
• Osmosis: Solvent moves through a semipermeable membrane from a dilute to a
concentrated solution, equalizing concentrations.
• Osmotic Pressure: The driving force behind osmosis, varying based on the solute's
nature.
lunatic
• Non-electrolyte Solutes: Contain molecules; osmotic pressure depends on solute Pig
concentration.
• Electrolyte Solutes: Contain ions; osmotic pressure depends on solute concentration
and degree of dissociation. clomadic
Coil C freak's
7
Like osmotic pressure, the other colligative properties of
solutions, vapor pressure, boiling point, and freezing point,
depend on the number of particles in solution

overthe counter
0171 9
P

Isotonic and Buffer Solutions

• Isosmotic Solutions: Have the same osmotic pressure; designed for comfort, efficacy,
and safety in medical applications.
• Isotonic Solutions: Have the same osmotic pressure as a specific body fluid (e.g., blood,
eye fluid).
• Hypotonic Solutions: Lower osmotic pressure than a body fluid.
• Hypertonic Solutions: Higher osmotic pressure than a body fluid.
• Pharmaceutical Applications: Dosage forms for blood, eye, nose, and bowel must align
with the osmotic properties of body fluids for safety and effectiveness.

Jbcisle
111 15110
is omit

10 an Pinpsodenda 10
 Special Clinical Considerations of Tonicity
• Isotonic Solutions: Preferred for ophthalmic and parenteral use; maintain homeostasis
with body fluids.
• Hypertonic Solutions: Used in specific cases to draw fluids from edematous tissues.
• Ophthalmic Preparations: Typically isotonic to replicate tears; buffered to reduce
irritation and enhance stability.
µ • Non-Isotonic Injections: Administered slowly and in small amounts to minimize irritation
and fluid imbalance.
• Small vs. Large Volumes: Small-volume injections are less concerning when diluted by
large-volume infusions.
• Risks of Hypotonic Infusions: Can cause osmotic hemolysis and fluid overload.
• Risks of Hypertonic Infusions: May lead to hyperglycemia, diuresis, and electrolyte
imbalance.
• Excessive Isotonic Infusions: Can overload the circulatory system if given in large
volumes or at excessive rates.

Miskibik 88 173717701715Gt
dose
1111701 ON wed 17130104808 11
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 for 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

12
Preparation of Isotonic Solutions
• When one gram molecular weight of any nonelectrolyte, that is, a substance with negligible
dissociation, such as boric acid, is dissolved in 1000 g of water, the freezing point of the solution is
about 1.86C below the freezing point of pure water
• By simple proportion, therefore, we can calculate the weight of any nonelectrolyte that should be
dissolved in each 1000 g of water if the solution is to be isotonic with body fluids
• Boric acid, for 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

>>> 17.3 g of boric acid in 1000 g of water, having a weight-in-volume strength of 1.73%, should make a
solution isotonic with lacrimal fluid

13
Preparation of Isotonic Solutions
• Osmotic pressure depends more on the number than on the kind of particles
• Substances that dissociate have a tonic effect that increases with the degree of dissociation; the
greater the dissociation, the smaller the quantity required to produce any given osmotic pressure
• 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
nonelectrolyte 34 1013 812TH
• This dissociation factor, 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)

>>>Hence, 9.09 g of sodium chloride in 1000 g of water should make a solution isotonic with blood
or lacrimal fluid
• In practice, a 0.90% w/v sodium chloride solution is considered isotonic with body fluids
14
Calculations of the i Factor
➢ Zinc sulfate is a 2-ion electrolyte, dissociating 40% in a certain concentration. Calculate its
dissociation (i) factor.
On the basis of 40% dissociation, 100 particles of zinc sulfate will yield:
40 zinc ions + 40 sulfate ions + 60 undissociated particles = 140 particles
Because 140 particles represent 1.4 times as many particles as were present before dissociation,
the dissociation (i) factor is 1.4.
14090

➢ Zinc chloride is a 3-ion electrolyte, dissociating 80% in a certain concentration. Calculate its dissociation
(i) factor.
On the basis of 80% dissociation, 100 particles of zinc chloride will yield:
80 zinc ions + 80 chloride ions + 80 chloride ions + 20 undissociated particles = 260 particles
Because 260 particles represents 2.6 times as many particles as were present before dissociation,
the dissociation (i) factor is 2.6. Zinc chloride

15
Preparation of Isotonic Solutions
• Isotonic solutions may then be calculated by using this formula

• The value of i for many a medicinal salt has not been experimentally determined
• 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:

Nonelectrolytes and substances of slight dissociation1.0

Substances that dissociate into 2 ions: 1.8
Substances that dissociate into 3 ions: 2.6
Substances that dissociate into 4 ions: 3.4
Substances that dissociate into 5 ions: 4.2

16
Preparation of Isotonic Solutions
• A special problem arises when a prescription directs us to make a solution isotonic by adding the proper
amount of some substance other than the active ingredient or ingredients
• Given a 0.5% w/v solution of sodium chloride, we may easily calculate that 0.9 g - 0.5 g = 0.4 g of additional
sodium chloride that should be contained in each 100 mL if the solution is to be made isotonic with a body
fluid
➢ How much sodium chloride should be used in preparing 100 mL of a 1% w/v solution of atropine sulfate,
which is to be made isotonic with lacrimal fluid?
The answer depends on how much sodium chloride is in effect represented by the atropine sulfate

17
Preparation of Isotonic Solutions
• The relative tonic effect of two substances—that is, the quantity of one that is the equivalent in tonic effects
to a given quantity of the other—may be calculated if the quantity of one having a certain effect in a
specified quantity of solvent is divided by the quantity of the other having the same effect in the same
quantity of solvent.
• For example, we calculated that 17.3 g of boric acid per 1000 g of water and 9.09 g of sodium chloride per
1000 g of water are both instrumental in making an aqueous solution isotonic with lacrimal fluid
• If, however, 17.3 g of boric acid are equivalent in tonicity to 9.09 g of sodium chloride, then 1 g of boric acid
must be the equivalent of 9.09 g 17.3 g or 0.52 g of sodium chloride
• Similarly, 1 g of sodium chloride must be the ‘‘tonicic equivalent’’ of 17.3 g9.09 g or 1.90 g of boric acid
• The relative quantity of sodium chloride that is the tonicic equivalent of a quantity of boric acid may be
calculated by these ratios

Sodium chloride (MW=58.5)

Boric acid (MW=61.8)

18
Preparation of Isotonic Solutions
• Quantitiesof two substances that are tonicic equivalents are proportional to the molecular weights of each
multiplied by the i value of the other

➢ How much sodium chloride should be used in preparing 100 mL of a 1% w/v solution of atropine sulfate,
which is to be made isotonic with lacrimal fluid?
MW of sodium chloride = 58.5; i=1.8
MW of atropine sulfate = 695; i=2.6

X = 0.12 g of sodium chloride represented by 1 g of atropine sulfate

Because a solution isotonic with lacrimal fluid should contain the equivalent of 0.90 g of sodium chloride in
each 100 mL of solution, the difference to be added must be 0.90 g - 0.12 g = 0.78 g of sodium chloride

19
Preparation of Isotonic Solutions
Sodium chloride equivalents (E values)
If the number of grams of a substance included in a prescription is multiplied by its sodium chloride equivalent,
the amount of sodium chloride represented by that substance is determined

20
Calculations of the Sodium Chloride Equivalent
• The sodium chloride equivalent of a substance may be calculated as follows:

Papaverine hydrochloride (m.w. 376) is a 2-ion electrolyte, dissociating 80% in a given concentration.

Calculate its sodium chloride equivalent.

Because papaverine hydrochloride is a 2-ion electrolyte, dissociating 80%, its i factor is 1.8.

21
Calculations of Tonicic Agent Required
• How many grams of sodium chloride should be used in compounding the following prescription?

Pilocarpine nitrate MW = 271 g/mol

8
IF
Step 1. 0.23 x 0.3 g = 0.069 g of sodium chloride represented by the pilocarpine nitrate
Step 2. 30 x 0.009 = 0.270 g of sodium chloride in 30 mL of an isotonic sodium chloride solution
Step 3. 0.270 g (from Step 2) - 0.069 g (from Step 1) = 0.201 g of sodium chloride to be used, answer.

22
Calculations of Tonicic Agent Required
• How many grams of boric acid should be used in compounding the following prescription?

The prescription calls for 0.6 g of phenacaine

hydrochloride and 0.3 g of chlorobutanol.

Step 1. 0.20 x 0.6 g = 0.120 g of sodium chloride represented by phenacaine hydrochloride

0.24 x 0.3 g = 0.072 g of sodium chloride represented by chlorobutanol
Total: 0.192 g of sodium chloride represented by both ingredients
Step 2. 60 x 0.009 = 0.540 g of sodium chloride in 60 mL of an isotonic sodium chloride solution
Step 3. 0.540 g (from Step 2) - 0.192 g (from Step 1) = 0.348 g of sodium chloride required to make the solution

But because the prescription calls for boric acid:

Step 4. 0.348 g x 0.52 (sodium chloride equivalent of boric acid) = 0.669 g of boric acid to be used, answer.

23
Isotonicity

24
Buffers and Buffer Solutions
• When a minute trace of hydrochloric acid is added to pure water, a significant increase in hydrogen-ion
concentration occurs immediately
• In a similar manner, when a minute trace of sodium hydroxide is added to pure water, it causes a
correspondingly large increase in the hydroxyl-ion concentration
• These changes take place because water alone cannot neutralize even traces of acid or base, that is, it has
no ability to resist changes in hydrogen-ion concentration or pH
• A solution of a neutral salt, such as sodium chloride, also lacks this ability. Therefore, it is said to be
unbuffered

25
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, even with the addition of materials that
may be expected to change the hydrogen–ion concentration
• These substances or combinations of substances are called buffers; their ability to resist changes in pH
• is referred to as buffer action; their efficiency is measured by the function known as buffer capacity; and
solutions of them are called buffer solutions
• By definition, a buffer solution is a system, usually an aqueous solution, that possesses the property of
resisting changes in pH with the addition of small amounts of a strong acid or base

26
Buffers and Buffer Solutions
In pharmacy, the most common buffer systems are used in:
1. the preparation of such dosage forms as injections and ophthalmic solutions, which are placed
directly into pH-sensitive body fluids
2. the manufacture of formulations in which the pH must be maintained at a relatively constant
level to ensure maximum product stability
3. pharmaceutical tests and assays requiring adjustment to or maintenance of a specific pH for
analytic purposes

27
Buffers and Buffer Solutions
A buffer solution is usually composed of
• a weak acid and a salt of the acid, such as acetic acid and sodium acetate
• a weak base and a salt of the base, such as ammonium hydroxide and ammonium chloride

Typical buffer systems that may be used in pharmaceutical formulations include the following pairs:
• acetic acid and sodium acetate
• boric acid and sodium borate
• disodium phosphate and sodium acid phosphate

28
Buffers and Buffer Solutions
• In the selection of a buffer system, due consideration must be given to the dissociation constant
of the weak acid or base to ensure maximum buffer capacity
• This dissociation constant (Ka), in the case of an acid, is a measure of the strength of the acid; the
more readily the acid dissociates, the higher its dissociation constant and the stronger the acid

Dissociation of an acid:

Henderson-Hasselbalch equation
pH = acidity (pH value) of a solution (pH = -log (H+)
Ka = disassociation constant of the acid
pKa = negative logarithm of Ka (pKa = - log Ka)
[HA] = concentration of an acid
[A-] = concentration of conjugate base (salt)

29
Buffers and Buffer Solutions
Henderson-Hasselbalch equation (Buffer equation)

Weak acid
Kw: the ion-product constant of liquid water
Weak base Kw value for water is 10-14 at 25°C,
pKw should always equal 14

The buffer equation is useful for calculating

(1) the pH of a buffer system if its composition is known
(2) the molar ratio of the components of a buffer system required to give a solution of a desired pH

The equation can also be used to calculate the change in pH of a buffered solution with the addition
of a given amount of acid or base

30
Buffers and Buffer Solutions
Calculating the pH value:
What is the pH of a buffer solution prepared with 0.05 M
sodium borate and 0.005 M boric acid?
The pKa value of boric acid is 9.24 at 25C.

What is the pH of a buffer solution prepared with 0.05 M

ammonia and 0.05 M ammonium chloride?
The Kb value of ammonia is 1.80 x 10-5 at 25C.
pKb = - log Kb = - log 1.80 x 10-5 = 4.74

31
Buffers and Buffer Solutions
Calculating the molar ratio of salt/acid required to prepare a buffer system with a desired pH value:

What molar ratio of salt/acid is required to prepare a sodium acetate-acetic acid buffer solution
with a pH of 5.76? The pKa value of acetic acid is 4.76 at 25C.

32
Buffers and Buffer Solutions
Calculating the amounts of the components of a buffer solution required to prepare a desired volume, given
the molar ratio of the components and the total buffer concentration:
The molar ratio of sodium acetate to acetic acid in a buffer solution with a pH of 5.76 is 10:1.
Assuming the total buffer concentration is 2.2 x 10-2 mol/L, how many grams of sodium acetate (MW=82) and
how many grams of acetic acid (MW=60) should be used in preparing a liter of the solution?
Because the molar ratio of sodium acetate to acetic acid is 10:1
the mole fraction of sodium acetate = 10 / (10+1) = 10/11
the mole fraction of acetic acid = 1/(10+1) = 1/11
If the total buffer concentration 2.2 x 10-2 mol/L,
the concentration of sodium acetate = (10/11) x 2.2 x 10-2 mol/L = 2.0 x 10-2 mol/L
the concentration of sodium acetate = (1/11) x 2.2 x 10-2 mol/L = 0.2 x 10-2 mol/L

then 2.0 x 10-2 (=0.02) x 82 = 1.64 g of sodium acetate per liter of solution, and
0.2 x 10-2 (=0.002) x 60 = 0.120 g of acetic acid per liter of solution, answers.

33
Buffers and Buffer Solutions
The efficiency of buffer solutions-that is, their specific ability to resist changes in pH-is measured in terms of
buffer capacity; the smaller the pH change with the addition of a given amount of acid or base, the greater
the buffer capacity of the system

The buffer capacity of a system depends on

(1) the relative concentration of the buffer components
(2) the ratio of the components

For example, a 0.5 M-acetate buffer at a pH of 4.76 would have a higher buffer capacity than a 0.05 M-buffer.

If a strong base such as sodium hydroxide is added to a buffer system consisting of equimolar concentrations of
sodium acetate and acetic acid, the base is neutralized by the acetic acid forming more sodium acetate, and
the resulting increase in pH is slight

In a similar manner, the addition of a strong acid to a buffer system consisting of a weak base and its salt would
produce only a small decrease in pH

34
Buffers and Buffer Solutions
Calculating the change in pH of a buffer solution with the addition of a given amount of acid or base:

Calculate the change in pH after adding 0.04 mol of sodium hydroxide to a liter of a buffer solution containing
0.2 M concentrations of sodium acetate and acetic acid.
The pKa value of acetic acid is 4.76 at 25C.

The pH of the buffer solution is calculated by using the buffer equation as follows:

The addition of 0.04 mol of sodium hydroxide converts 0.04 mol of acetic acid
to 0.04 mol of sodium acetate.
Consequently, the concentration of acetic acid is decreased and the
concentration of sodium acetate is increased by equal amounts, according to
the following equation:

35