Pharmaceutics 1 Lecture notes, lectures weeks 3-4 PDF

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Pharmaceutics 1 • • • • • • •

Overview of dose-forms Doses and calculations Properties of solids Overview of analysis Solutions Flow behaviour Surface properties

The dose • Oral (or enteral) – Sub-lingual and buccal – Oral – Rectal

• Parenteral – – – – –

Injected Pulmonary Transdermal Ophthalmic, nasal Vaginal

The dose • Oral (or enteral) vs parenteral • Systemic vs local • How is dose expressed? – As a number of milligrams (or millilitres) etc – By relating the dose to patient body-weight

Expression of dose • Mrs Smith is instructed to “take one tablet” • Mr Chung is to be given an injection of drug while he is in hospital. The instruction says “the patient is to receive 3 mg/kg by injection” What other information do we need about Mr Chung?

The dose • Oral (or enteral) vs parenteral • Systemic vs local • How is dose expressed? – As a number of milligrams (or millilitres) etc – By relating the dose to patient body-weight

• What is the dose frequency?

The dose frequency • Mrs Sharard is instructed to “take one tablet three times daily for seven days” Let’s assume each tablet contains 20mg of drug.

 What is the daily dose taken?  What is the total dose taken?

Usual dose and dose range Usual dose

0 Dose range

Amount given

Under-dose and over-dose Under-dose

Overdose Usual dose

0 Dose range

Amount given

The dose • • • • •

Oral (or enteral) vs parenteral Systemic vs local Usual dose or dose-range Overdose and underdose Information sources for dose

The dose • • • • • •

Oral (or enteral) vs parenteral Systemic vs local Usual dose or dose-range Overdose and underdose Information sources for dose Resistance vs sensitivity

The dose • • • • • • • •

Oral (or enteral) vs parenteral Systemic vs local Usual dose or dose-range Overdose and underdose Information sources for dose Resistance vs sensitivity Paediatric doses Dosage regimen

Importance of calculations

and communication

Australian Commission on Safety and Quality in Healthcare – http://www.safetyandquality.gov.au/

•

National terminology, abbreviations and symbols to be used in the prescribing and administering of medicines in Australian hospitals – http://www.safetyandquality.gov.au/publications/national-terminology-abbreviation s-and-symbols-to-be-used-in-the-prescribing-and-administering-of-medicines-in-aus tralian-hospitals /

How the body handles the dose

Give the patient an oral dose of a drug

How the body handles the dose Drug concentration in blood

Give the patient an oral dose of a drug

Time after administration

How the body handles the dose Drug concentration in blood

Drug absorption phase

Time after administration

How the body handles the dose Drug concentration in blood

Drug elimination phase

Time after administration

Some “landmarks” Toxic concentration

Drug concentration in blood

Minimum effective concentration

Time after administration

Some “landmarks” Drug concentration in blood Duration of action

Minimum effective concentration

Time after administration

Some “landmarks” Drug concentration in blood

Minimum effective concentration

Onset time

Time after administration

Some “landmarks” Drug concentration in blood

Therapeutic window

Time after administration

Intravenous (IV) injection Drug concentration in blood

All you see is the elimination phase

Time after administration

The majority of drugs are measured by mass or volume

Some key points about mass and volume • • • • •

Avoid the symbol  Weight per millilitre (g/mL) (implies liquid) Density (g/cm3) (implies solid) Weight / mL  Density (assumed equal) Specific Gravity (wt/mL of x )/(wt/mL of water)

• USE CORRESPONDING UNITS

Mechanical balances vs.....

beam balance

Mettler digital balance

Error in measurement absolute error

Relative error (%) 100  amount weighed

MWA 100 

absolute error Relative error (%)

Error in measurement absolute error

Relative error (%) 100  amount weighed For most drugs, the minimum amount that should be weighed on a mechanical dispensing balance is 100mg MWA 100 

absolute error Relative error (%)

How de we measure liquids?

www.proscitech.com.au

http://www.jaytecglass.co.uk/ConicalMeasuresGovernmentStamped.php

What to do when the amount needed is less than the MWA

Points to ponder • Amount vs concentration

Amount vs Concentration  Mass  Volume Quantity (Q)

 Moles  Equivalents

Amount vs Concentration

Quantity

Amount vs Concentration

Quantity

Concentration = quantity / volume

Points to ponder • Amount vs concentration • Percentage concentrations

Percentage concentrations • weight / volume

Percentage w/v 100mL mark -

Solid drug powder

Percentage w/v 100mL mark

Percentage (w/v) is based on a product made up to 100 mL

Percentage w/v 100mL mark

Percentage (w/v) is based on a product made up to 100 mL

More generally ….

Percentage is based on a product made up to 100 mL (or 100 g)

You must use corresponding units e.g. 5 %w/v

=

You must use corresponding units e.g. 5 %w/v

= 5 grams per 100 mL

You must use corresponding units e.g. 5 %w/v

= 5 grams per 100 mL

0.1 %v/v

=

You must use corresponding units e.g. 5 %w/v

= 5 grams per 100 mL

0.1 %v/v

= 0.1 mL per 100 mL

You must use corresponding units e.g. 5 %w/v

= 5 grams per 100 mL

0.1 %v/v

= 0.1 mL per 100 mL

1 in 50 (w/v) =

You must use corresponding units e.g. 5 %w/v

= 5 grams per 100 mL

0.1 %v/v

= 0.1 mL per 100 mL

1 in 50 (w/v) = 1 gram per 50 mL = 2 gram per 100 mL = 2 % w/v

You must understand common multipliers

nanogram

1000x

microgram

milligram

1000x

1000x

1000000x or 106

gram

kilogram

1000x

You must understand common multipliers 10-3

nanogram

microgram

milligram

gram

kilogram

You must understand common multipliers 10-3

microlitre

1000x

millilitre

1000x

litre

Molar concentrations • Moles per 1000mL solution • Millimoles per 1000mL solution • Units g/mol or mg/mmol

Percentage concentrations • weight / volume



solid in a mixture

• weight / weight



solid in a cream

• volume / volume



liquid in a mixture

• volume / weight



aromatic oil in a bulk powder

Percentage concentrations APF conventions . . .

Solids by weight, liquids by volume, unless otherwise specified. VERY important concept

Cetomacrogol (Sorbolene) Cream APF Cetomacrogol Emulsifying Wax Liquid Paraffin (by weight) White Soft Paraffin Chlorocresol Propylene Glycol (made up) Purified water to

15 10 10 0.1 5 100

g g g g mL g

What if 30g cream required?

Calculate quantities for the formula

Ephedrine

30 mg

Sod Phenobarbitone

100 mg

Syrup

2 mL

Conc Chloroform Water

0.25 mL

Water Mitte 100mL

to

10 mL

Calculate quantities for the formula

Wool fat

5 parts

Olive oil (wt/mL 0.91)

10 parts

White soft paraffin

20 parts

Zinc Oxide Mitte 60g

2 parts

Points to ponder • Amount vs concentration • Percentage concentrations • % w/v vs % w/w

Points to ponder • Amount vs concentration • Percentage concentrations • % w/w vs % w/v

Syrup BP is about 67% w/w Sucrose so, 67 g Sucrose per 100 g Syrup

Points to ponder • Amount vs concentration • Percentage concentrations • % w/w vs % w/v Weight per mL

Therefore 67 g Sucrose per 100 g / 1.32 g/mL Syrup. Namely, 67 g Sucrose per 75.8 mL of Syrup.

Ratio strength Convert 0.01% to ratio strength

Convert 1:5000 (w/v) ratio strength into %

Convert 2 mg/mL into ratio strength

Points to ponder • Amount vs concentration • Percentage concentrations • % w/w vs % w/v • Ethanol vs alcohol

Mixing ethanol and water  Evolution of gas bubbles (i.e. air)  Solution warms up  Volume shrinks (contracts) Water Alcohol xx% Ethanol

Mixing ethanol and water V T < V 1 + V2

Water

V1 VT

Ethanol

V2

Alcohol xx%

Mixing ethanol and water WT = W1 + W 2 Volume lost, but weight conserved Water

W1 WT

Ethanol

W2

Alcohol xx%

Points to ponder • Amount vs concentration • Ethanol vs alcohol • Percentage concentrations • % w/w vs % w/v • Milli-equivalents and tonicity

Equivalents (and milliequivalents) a measure of quantity based on charge You need to remember that . . .

Number of equivalents

= Number of moles X Valence

Absolute value

Equivalents (and milliequivalents) and therefore . . .

Number of = millimoles X Valence milliequivalents

Tonicity Solution has lower osmotic  Hypotonic pressure than cellular fluid

Solution has higher osmotic  Hypertonic pressure than cellular fluid

Osmotic pressure Cell High osmotic pressure



 “Hypertonic”

Cell undergoes shrinkage (or crenation) due to water loss in a hypertonic environment = TISSUE IRRITATION.

Osmotic pressure Low osmotic pressure



 “Hypotonic”

Cell undergoes (swelling) due to water uptake in a hypotonic environment.

Osmotic pressure Low osmotic pressure



 “Hypotonic”

Cell rupture = CELL DEATH

Products intended to contact delicate membranes should be formulated in an isotonic vehicle to minimise tissue irritation and injury. Add an inert substance (usually sodium chloride or glucose) to hypotonic products to render them isotonic

Adjusting to make solution isotonic (1) Freezing point depression method

FD C (%) FD1% Assumes that FD is directly proportional to concentration

Adjusting to make solution isotonic • Freezing point depression method

FD C(%) FD1% a =  FD

0.52 - a W%  b

b is the FD1% of adjusting solute

Adjusting to make solution isotonic (2) Sodium Chloride Equivalents (SCE) method

W%  0.9 -  (Cdrug A SCE drug A)  (Cdrug B SCE drug B )  ...



Example 1 Convert 0.01% to ratio strength

Example 1 Convert 0.01% to ratio strength

Example 2 Convert 1:5000 (w/v) ratio strength into %

Example 2 Convert 1:5000 (w/v) ratio strength into %

Example 3 Convert 2 mg/mL into ratio strength

Example 3 Convert 2 mg/mL into ratio strength

Example 3 Convert 2 mg/mL into ratio strength

Example 3 Convert 2 mg/mL into ratio strength

Example 4 Convert 2 ppm into % and ratio strength

Example 4 Convert 2 ppm into % and ratio strength

Example 5 What volume of dye (1% w/v) needed to make 500mL of 1 : 20,000?

Example 5 What volume of dye (1% w/v) needed to make 500mL of 1 : 20,000?

Example 5 What volume of dye (1% w/v) needed to make 500mL of 1 : 20,000?

A 0.005 %w/v solution contains 0.005g per 100mL  500mL contains 0.025g

Example 5 What volume of dye (1% w/v) needed to make 500mL of 1 : 20,000?

A 0.005 %w/v solution contains 0.005g per 100mL  500mL contains 0.025g

Example 6 What volume of Alcohol 90% needed to make 150 mL of Alcohol 50%?

Example 6 What volume of Alcohol 90% needed to make 150 mL of Alcohol 50%?

 150mL Alcohol 50% contains

mL Ethanol

Example 6 What volume of Alcohol 90% needed to make 150 mL of Alcohol 50%?

Example 6 What volume of Alcohol 90% needed to make 150 mL of Alcohol 50%?

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

When you mix ethanol (or Alcohol x%) with water ….

 A gas is evolved and escapes as bubbles  The mixture feels a bit warmer initially but then cools down  The volume contracts

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

When you mix ethanol (or Alcohol x%) with water ….

 A gas is evolved and escapes as bubbles  The mixture feels a bit warmer initially but then cools down  The volume contracts

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?  A gas is evolved and escapes as bubbles  The mixture feels a bit warmer initially but then cools down  The volume contracts 50 mL water 50 mL ethanol

Less than 100mL solution

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?  A gas is evolved and escapes as bubbles  The mixture feels a bit warmer initially but then cools down  The volume contracts but the weight is maintained 50 g water 50 g ethanol

100g of solution

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?  A gas is evolved and escapes as bubbles  The mixture feels a bit warmer initially but then cools down  The volume contracts but the weight is maintained

Therefore, you need to think about both the volumes and weights of the alcohols and water in this problem

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

So, what do you know?

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

So, what do you know? Volume of Alcohol 90% but not the Alcohol 60% Weight / mL of both alcohols Weight / mL of water

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

20 L of Alcohol 90% contains 18 L ethanol

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

You were also told the weight / mL of both alcohols 30 L of Alcohol 60% = 20 L of Alcohol 90% =

Example 7 How much water is needed to add to 20 litres Alcohol 90% to produce Alcohol 60%?

You were also told the weight / mL of both alcohols 30 L of Alcohol 60% = 20 L of Alcohol 90% = Weight difference

=

Example 8 What vol of conc Phosphoric Ac (85% w/w H3PO4, wt/mL = 1.72g) needed to make 500mL of dilute Phosphoric Ac (10% w/w H3PO4, wt/mL = 1.055g)? Weight of 500mL diluted acid = 500mL X 1.055g/mL = 527.5g This contains 52.75g H3PO4

Example 8 What vol of conc Phosphoric Ac (85% w/w H3PO4, wt/mL = 1.72g) needed to make 500mL of dilute Phosphoric Ac (10% w/w H3PO4, wt/mL = 1.055g)? Weight of 500mL diluted acid = 500mL X 1.055g/mL = 527.5g This contains 52.75g H3PO4

Example 8 What vol of conc Phosphoric Ac (85% w/w H3PO4, wt/mL = 1.72g) needed to make 500mL of dilute Phosphoric Ac (10% w/w H3PO4, wt/mL = 1.055g)?

Example 8 What vol of conc Phosphoric Ac (85% w/w H3PO4, wt/mL = 1.72g) needed to make 500mL of dilute Phosphoric Ac (10% w/w H3PO4, wt/mL = 1.055g)?

Example 9 Calculate quantities for the formula

Ephedrine

30 mg

Sod Phenobarbitone

100 mg

Syrup

2 mL

Conc Chloroform Water

0.25 mL

Water Mitte 100mL

to

10 mL

Example 10 Calculate quantities for the formula

Wool fat

5 parts

Olive oil (wt/mL 0.91)

10 parts

White soft paraffin

20 parts

Zinc Oxide Mitte 60g

2 parts

Example 10 Calculate quantities for the formula

Wool fat

5

Olive oil (wt/mL 0.91)

10

White soft paraffin

20

Zinc Oxide Mitte 60g

2

Example 11 Calculate the molarities of solutions of sodium chloride that contain either (a) 29.25 g or (b) 58.5 mg dissolved in water to 1000mL. (MW 58.5 g/mole)

Equivalents A measure of quantity based on charge

Equivalents A measure of quantity based on charge

Example 12 Calculate the number of meq / L of ions in (a) 1mM sodium chloride and (b) 1mM calcium chloride. (a) 1mmole NaCl = 1 mmole sodium ions + 1 mmole chloride ions

Example 12 Calculate the number of meq / L of ions in (a) 1mM sodium chloride and (b) 1mM calcium chloride. (b) 1mmole CaCl2 = 1 mmole calcium ions + 2 mmole chloride ions

Methods to adjust tonicity • Freezing point depression (FD)

Freezing point depression of unadjusted product FD1% of adjusting solute (e.g. 0.576 for sodium chloride)

Example 13 Calculate quantity of sodium chloride for the formula Atropine Sulphate

0.25%

Sodium chloride

q.s.

Water

ad

100

Mitte 20mL

FD1% of sodium chloride (0.576)

Example 13 Calculate quantity of sodium chloride for the formula Atropine Sulphate

0.25%

Sodium chloride

q.s.

Water Mitte 20mL

ad

100

 175mg

Methods to adjust tonicity • Sodium chloride equivalents (SCE)

The SCE of a drug is the weight of sodium chloride (grams) osmotically equivalent to 1 gram of a drug.

Example 14 Calculate quantity of sodium chloride for the formula Atropine Sulphate

0.25%

Sodium chloride

q.s.

Water

ad

 175mg

100

Mitte 20mL

W% = 0.9 - (0.12 x 0.25) = 0.87%

Notes  Examples 13 and 14 almost the same answer  FD method works for sodium chloride and glucose (just use the FD1% of glucose)  SCE method only calculates for sodium chloride...