Buffered & Isotonic Solutions

Question 1

Importance of having a buffered and isotonic/isosmotic solution?

Answer 1

During formulation every parameter is considered to maximise solubility and stability as designed to last 2 years. Also, physiological differences with site of delivery are minimised - reducing adverse effects. So liquid formulation (solution) must be buffered etc.

Question 2

Buffers in oral solutions & eye drops. Discuss..

Answer 2

pH of acidic solution usually controlled by salt form or by traditional buffers e.g. HCl, tartaric acid, benzoic or citric acid

Question 3

Buffers in injectable solutions. Discuss…

Answer 3

Drug often solubilized at desired concentration by pH adjustment

Drug pKa must be far enough from formulation pH

Question 4

pH range for IV and IM injections?

Answer 4

pH 2-12

Question 5

pH range for subcutaneous (SC) injections - why?

Answer 5

2.7-9.0

Dilution rate is reduced and results in irritation at the injection site

Question 6

Normal pH for therapeutic antibody solution?

Answer 6

5.5

Question 7

% ionisation when 2 pH units above/below pKa?

Answer 7

99%

Question 8

In pharmacy, how is the pH of injectable solutions controlled?

Answer 8

By the salt form of the drug, strong acids/bases (e.g. HCl, NaOH) or a buffer solution made from a weak acid and a salt of this acid (HH equation)

Question 9

Why is a buffer effective? Limitations?

Answer 9

Because solubility of a drug is pH dependent so the buffer maintains the solubility of the drug

Needs to be carefully chosen to be stable. pH range extends +/- 1 pH unit around the pKa

Concentration of buffer should control pH but not affect physiological functions i.e. not cause adverse effects

Question 10

What is osmotic pressure?

How is it measured?

Answer 10

In osmosis when water and molecules cross the membrane, the movement creates pressure on one side of the membrane. The pressure is applied to oppose the swelling on the membrane. This is osmotic pressure (pressure applied to solution to prevent osmosis)

Measured by the difference in volume/seen as height of solution

Question 11

Osmosis, osmotic pressure and drug concentration

Van’t Hoff relation

Answer 11

Osmosis leads to a decrease of the non-permeant solute/drug concentration.

The osmotic pressure is a colligative property i.e. depends on the number of molecules/moles in the solution

Question 12

Define Isotonic

Drug formulation?

Answer 12

Concentration in the environment is similar to within the cell - balance

Drugs must be made isotonic/isosmotic before administration

Isotonic correction depends on type of membrane as well as drug

Question 13

Define Hypotonic

Answer 13

Solute concentration is higher WITHIN the cells - water moves in (can lead to bursting)

Question 14

Define Hypertonic

Answer 14

Solute concentration is higher OUTSIDE the cells - water moves out (can lead to shrivelling)

Question 15

What is osmolarity?

Answer 15

It is a property of the solution and is independent of the type of membrane. It is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre

Question 16

What is osmolality?

Answer 16

The number of osmoles/1kg of solvent

Question 17

What would happen if you had 2 isosmotic solutions on either side of a semi-permeable membrane?

Answer 17

No net transport from one side to the other as solutions have equal number of molecules.

Question 18

What is tonicity?

Answer 18

A measure of the osmotic pressure exerted on a membrane. It is specific to the membrane and the number of moles.

Question 19

Most common method of adjusting tonicity?

Answer 19

Freezing point depression. It is the difference between freezing point of water and freezing point of solution.

It is a colligative property of the osmotic pressure.

i.e. Addition of x grams of a solute will cause the freezing point to shift to the left, depending on the amount you add