W7 Oral Solution: Dosage Forms l

Question 1

What are some examples of pharmaceutical solutions?

Answer 1

Injections, eye and ear drops, enemas, vaginal douches, topical solutions, nebulisers.

Question 2

Definition of a pharmaceutical solution

Answer 2

Pharmaceutical solutions = liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system

Question 3

What is the advantage of liquid oral dosage forms?

(solution)

Answer 3

Absorption from is often
- Rapid and complete
- Greater bioavailability

Question 4

Advantages and Disadvantages of pharmaceutical products as solutions

Answer 4

Advantages

1. Easily administered for individuals who have difficulty in swallowing, e.g. elderly patients, infants
2. The therapeutic agent is dissolved in the formulation and is therefore immediately available for absorption (Provided the drug does not precipitate within the GI tract)
3. Taste-masking of bitter therapeutic agents

Disadvantages

1. Unsuitable for therapeutic agents that are chemically unstable in the presence of water
2. The poor solubility of certain therapeutic agents may prohibit their formulation as pharmaceutical solutions
3. Expensive to ship and are bulky for the patient to carry

Question 5

Excipients in solution

Question 6

How is Water used in pharmaceutical solutions?

Answer 6

• Tap drinking water not normally used for the manufacture of pharmaceutical solutions / extemporaneous compounding
• Purified by distillation, ion exchange, or reverse osmosis  non-parenteral solutions
• Further purified to remove pyrogens (fever-producing compounds)  water for injections

Question 7

When a drug is ionised (charged) it is….

Answer 7

More water soluble

Question 8

Drug solubility
When a drug solubility is high, medium, low what changes if any are made?

Answer 8

Solubility at selected pH of formulation

High
Readily incorporated into the vehicle and formulated as an oral solution

Moderate
Solubility enhanced using co-solvents or by related methods (changing pH, salt conversion)

Low
Formulated as an alternative-dosage form, e.g. a suspension

Question 9

What is the pH range for oral administration

Answer 9

The acceptable pH range of solutions for oral administration is large, ranging from 5 to 8 pH units

Question 10

Co-solvent definition

Answer 10

Liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs.

Question 11

Approaches to help with drug solubilisation? (5)

Answer 11

Complexation such as;
1.Change pH
2.Add co solvent, 3.Change to a salt, 4.Make it into a disperse phase, 5.Make it more amorphous (so more water soluble)

Question 12

How to increase pourability and palatability

Answer 12

Decrease viscosity and add sweetners

Question 13

Qualitative vs Quantitative

Answer 13

pH paper is qualitative and a pH meter is quantitative

Question 14

Why are sweeteners added?
What are the main sweetening agents?

Answer 14

To increase the palatability of the therapeutic agent

Sucrose, liquid glucose, glycerol, sorbitol

Question 15

To mask the taste of the drug substance

Answer 15

Salty: butterscotch, apricot, peach, vanilla, wintergreen mint
Bitter: cherry, mint, anise
Sweet: vanilla, fruit, berry
Sour: citrus, raspberry

Question 16

Viscosity-enhancing agents:
How is viscosity increaser?

Answer 16

Increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers

Non-ionic (neutral) polymers:
Cellulose derivatives
Methylcellulose
Hydroxyethylcellulose
Hydroxypropylcellulose
Polyvinylpyrrolidone

Ionic polymers:
Sodium carboxymethylcellulose (anionic)
Sodium alginate (anionic)

Question 17

Antioxidants

Answer 17

To enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation
Antioxidants = Molecules that exhibit higher oxidative potential than the therapeutic agent, to inhibit free radical-induced drug decomposition
Examples:
Aqueous solutions
Sodium sulphite, sodium metabisulphite, sodium formaldehyde sulphoxylate and ascorbic acid
Oil-based solutions
Butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and propyl gallate.

Question 18

What are present in pharmaceutical oral solutions?

Answer 18

Active ingredient, water, buffer, co-solvent (vehicle), excipients, flavouring agents, sweeteners, preservatives, antioxidants, chelating agents, viscosity-modifying agents

Question 19

Preservatives

Answer 19

To control the microbial bioburden of the formulation
Ideal properties:
Broad antimicrobial spectrum (gram-positive, gram-negative bacteria and fungi)
Chemically and physically stable over the shelf-life of the product
Low toxicity
Examples:
Benzoic acid and salts
Sorbic acid and its salts
Alkyl esters of parahydroxybenzoic acid
A combination of two members enhances the antimicrobial spectrum
Typically methyl and propyl parahydroxybenzoates (in a ratio of 9:1)

Question 20

Chelating agents

Answer 20

To form complexes with heavy-metal ions involved in oxidative degradation of therapeutic agents
Ethylenediamine tetraacetic acid (EDTA)
Citric acid
Employed in conjunction with antioxidants

Question 21

Colourants

Question 22

Give examples of co-solvents?

Answer 22

Ethanol, glycerol, propylene glycol

Question 23

Antioxidant examples

Answer 23

Sodium metabisulphite, ascorbic acid

Question 24

Antimicrobial preservatives examples

Answer 24

Benzalkonium chloride, parabens, potassium sorbate

Question 25

pH adjusters examples

Answer 25

Citric acid, potassium phosphate

Question 26

Isotonicity adjusters

Answer 26

Sodium chloride, glucose

Question 27

Viscosity enhancers examples

Answer 27

Hydroxymethylcellulose

Question 28

Chelating agents examples

Answer 28

EDTA

Question 29

Flavours

Answer 29

Taste masking

Question 30

Sweeteners examples

Answer 30

Sucrose, sorbitol, mannitol, aspartame, sucralose

Question 31

Colouring agents example:

Answer 31

Dyes