Lecture 3 - Solution Dose Form

Question 1

Define a solution dose form

Answer 1

a solution is:
- thermodynamically stable
- 1-phase system
- composed of 2 or more components
- 1 of which is completely dissolved in the other

homogeneous b/c the solute is dispersed throughout the solvent in molecular or ionic sized particles

Question 2

Describe the desirable properties of a solution dose form

Answer 2

solutes may include active drug components, flavouring, coloring agents, preservatives, & stabilizers or buffering salts

water most common solvent for solutions, but ethanol, glycerin, propylene glycol, isopropyl alc or other liquids may be used, depending on the product req’s

Question 3

Describe the advantages of a solution dose form

Answer 3

• Solutions are completely homogenous (patients don’t need to shake it)
• Immediately available for absorption into the body (whereas capsules/tablets do have to be metabolized)
• Flexible in terms of dose adjustment
• May be used by any route of administration
• Can be administered to patients who cannot swallow tablets or capsules. (children/elderly etc.)

Question 4

Describe the disadvantages of a solution dose form

Answer 4

• Drugs less stable when in solution
• Some drugs not soluble in solvents that are acceptable for pharmaceutical use
• Drugs with objectionable taste require taste masking
• Heavier and bulkier than solids so are difficult to handle, package, transport, and store
• Require measurement by the patient or caregiver. Often less accurate than individual solid dosage forms, such as tablets and capsules (must rely on patient to measure correct dose)

Question 5

Discuss the process of dissolution

Answer 5

ΔHsoln = ΔH1 + ΔH2 + ΔH3
- ΔH1 and ΔH2 are both positive as energy required to overcome intermolecular forces. ΔH3 is negative because intermolecular bonds forming.
- For the solution process to be favorable, ΔH3 should at least equal ΔH1 + ΔH2.
- If both solvent and solute are non-polar, all the ΔH values are small. The major factor then is the increase in entropy that occurs when a solution does form. This is favorable for dissolution.

• If both solvent and solute are polar, all the ΔH values are large but similar in size. The major factor again is increase in entropy and dissolution is favored.
• Hence, like dissolves like.
• If a nonpolar solute like oil mixes with a polar solvent like water, ΔH1 is large and positive which outweighs ΔH3 so solution does not result.

Question 6

Identify the different solutes used in liquid dose forms & select a suitable solvent or blend of solvents for a specific product

Question 7

Calculate the displacement volume of a solute

Answer 7

The volume occupied by the powder when a suitable diluent is added during reconstitution of a drug
- Particularly important to take into account when dose needed only a proportion of the vial content
- Displacement volume for amoxicillin 250 mg is 0.2 mL so if 4.8 mL of diluent is added the resulting solution is amoxicillin 250 mg in 5 mL (50 mg/mL)

NB: displacement volume is different for each drug, for each strength of drug and for different brands/manufacturers formula).

Question 8

Identify the different solvents used in liquid dose forms & select a suitable solvent or blend of solvents for a specific product

Answer 8

Purified water USP
- Can be obtained using distillation, ion-exchange and reverse-osmosis
- Contains no added substances
- Cannot contain more than 0.001% of solids

Alcohol USP
- In pharmaceutical usage ‘alcohol’ refers to ethanol or ethyl alcohol
- Very useful solvent with preservative properties

Alcohol USP Cont’d
- For oral use in children:
– Under 6 years content should not exceed 0.5%
– For 6-12 years 5%
– Older than 12 years recommended maximum is 10%
- Water miscible
- Useful preparing solutions of drugs with limited solubility Methanol NEVER used pharmaceutically due to toxicity Isopropanol may be used in some topical preparations

Propylene glycol USP
- Miscible with alcohol and water
- May be used in combination with them or as a substitute for alcohol
- Some minor preservative activity
- Other polymeric glycols such as polyethylene glycol (PEG) and glycerin may be used
- Ethylene glycol is NEVER used due to toxicity

Question 9

Describe & contrast the different types of solution dose forms

Answer 9

Oral
- May contain excipients like sweeteners and preservatives
- Volumes per dose may include:
– Drop
– Teaspoonful (5 mL)
– Tablespoonful (15 mL)

Ophthalmic, otic and parenteral
- For use in eye, ear or injection

Topical
- For application to the skin
- Require ‘For external use’ auxillary label

Question 10

Discuss the role of preservatives in solution dose forms

Answer 10

Preservation of syrups…
Necessary to prevent microbial growth
– Quantity need depends on amount of free water (water available for microbial utilization)
– Concentration of preservative in free water must be effective but low enough to avoid toxicity

Simple syrup (sucrose 85%) contains no free water and is therefore self-preserving
If diluted to concentration <85% requires a preservative

Question 11

Calculate free water content of a product

Answer 11

do

Question 12

Calculate the quantity of preservative required for a specific product

Answer 12

do