Solutions and solubility: Pharmaceutical oral solutions

Question 1

Give an example of an extemporaneous formulation?

Answer 1

Thiamine (Vitamine B1) HCL oral liquid

Question 2

What s solubility affected by?

Answer 2

• pH

- Temperature (Drug should be in solution at all strengths

Question 3

List the four different types of solutions?

Answer 3

• Oral solutions
• Oral elixirs
• Oral syrups
• Others including mouthwashes, gargles, rectal solutions and enemas

Question 4

What are pharmaceutical oral solutions?

Answer 4

These are liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system.

Question 5

Pharmaceutical solutions for parental administration, or specific formulations require aseptic manufacture. TRUE OR FALSE?

Answer 5

TRUE

Question 6

What are the advantages of using oral solutions?

Answer 6

• Ease of use/ administration (i.e children or elderly)
• The drug is dissolved and readily available for absorption (As long as the drug is soluble in stomach it will have a greater bioavailability than solid dosage form)
• Modification of taste can improve compliance of bitter tasting drugs.

Question 7

What are the disadvantages of using oral solutions?

Answer 7

• Stability (cannot be used for drugs that are not stable in water e.g aspirin)
• Limited by the solubility of some drugs (only suitable for drugs with particular solubility profiles)
• Expensive to transport, compared to other dosage forms
• Bulky for patients to carry with them

Question 8

List the common types of excipients?

Answer 8

• Flavours and colours (sweeteners, dyes)
• Preservatives
• Vehicle (purified water)
• Co-solvents (glycerol, ethanol)
• Solubility enhancing agents (surfactants)
• Viscosity modifiers
• Buffers

Question 9

Solute-solute interactions are unfavourable but it is entropically viable. TRUE OR FALSE?

Answer 9

TRUE

Question 10

What are homogenous products?

Answer 10

Product must be in solution throughout all of the drugs shelf life, including excipients as well

Question 11

Solubility at selected pH may be high , moderate and low. TRUE OR FALSE?

Answer 11

TRUE

Question 12

What are the factors affecting solubility?

Answer 12

• Crystal form (polymorphism)
• Melting point
• Chemical factors (lipophilicity, ability to ionise)
• pH will affect the solubility of acids and bases

Question 13

At pH above the pKa, the solubility of acidic drugs increases. TRUE OR FALSE?

Answer 13

TRUE

Question 14

At pH below the pKa, the solubility of basic drugs increases. TRUE OR FALSE?

Answer 14

TRUE

Question 15

How do zwitterions behave?

Answer 15

They behave as acidic at basic pH and bases at acidic pH

Question 16

Which one of the following is most stable form of paracetamol, Monoclinic or Orthorhombic?

Answer 16

Monoclinic

Question 17

Orthorhombic undergoes plastic deformation due to a wellodefined planar structure and is suitable for direct compression. TRUE OR FALSE?

Answer 17

TRUE

Question 18

Are salts forms more water soluble than free acids/bases and more stable?

Answer 18

YES

Question 19

How can you optimise solubility?

Answer 19

• Salt form - more water soluble than free acid/base and more stable
• Modify pH - so salt form and ionised form predominates and solubility increases
• Co-solvents - Improves solubility for chemicals with poor aqueous solubility, but offer issues with toxicity

Question 20

What is Cyclodextrin used for?

Answer 20

Used for masking properties of drug

Question 21

What is Calixarene used for?

Answer 21

Used for masking properties of drugs, however, this is three dimensional. (they rotate and produce different conformations)

Question 22

Give an examples of aqueous vehicle?

Answer 22

Purified water Bp or USP prepared by distillation, ion exchange or reverse osmosis

Question 23

Purified water is not to be used for parental formulation ,water is used for injections. TRUE OR FALSE?

Answer 23

TRUE

Question 24

Give examples of co-solvents?

Answer 24

Glycerol - miscible in water
Alcohol USP
Surfactants

Question 25

Give examples of what do buffers do and provide examples?

Answer 25

Control pH, in doing so they maintain pH dependant solubility and optimise the product - They enhance stability of drugs that may be susceptible to acid or base catalysed hydrolysis - for example Acetates/citrate/phosphate buffered saline

Question 26

Give examples of Sweetening agents?

Answer 26

Sucrose/liquid glucose/glycerol

Question 27

Give examples of Viscosity modifiers?

Answer 27

Non ionic cellulose derivatives/ ionic polymers

Question 28

Give examples of the excipient antioxidants?

Answer 28

Sodium sulphite/ formaldehyde

Question 29

What are preservatives used for and give examples?

Answer 29

Used to control the microbial load in a formulation which should be kept below the minimum inhibitory concentration -E.g Parabens/ sodium benzoate

Question 30

Preservatives are not affected by other ingredients such as buffers, micelles or hydrophilic polymers. TRUE OR FALSE?

Answer 30

FALSE