Oral Solution Dosage Forms (w7)

Question 1

Define what pharmaceutical solutions are …

Answer 1

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

Question 2

What can limit the rate of absorption ?

Answer 2

Precipitation

Question 3

What are the advantages of pharmaceutical products as solutions?

Answer 3

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

Question 4

What are the disadvantages of pharmaceutical products as solutions ?

Answer 4

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

Question 5

Give some examples of Co-solvent excipients ….

Answer 5

• ethanol
• glycerol
• propylene glycol

Question 6

Give some examples of antioxidants excipients …

Answer 6

• sodium meta bisulphite
• ascorbic acid

Question 7

Give some examples of antimicrobial preservatives excipients …

Answer 7

• Benzalkonium chloride
• parabens
• potassium sorbate

Question 8

How is water purified to make pharmaceutical solutions?

Answer 8

ap 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 9

How is homogeneity attained in a formulation ?

Answer 9

• attainment of homogeneity in the formulation, due to limited aqueous solubility of the therapeutic agent

Question 10

What three stages does the dissolution of a therapeutic agent in water involve ?

Answer 10

1) Removal of a molecule of the drug from the solid state

2) Formation of a cavity within the solvent

3) Accommodation of the drug molecule into the formed cavity.

Question 11

What are the factors affecting the solubility of therapeutic agents ?

Answer 11

Physicochemical properties
-Molecular weight
-Particle size
-Solubility ∝ “1” /”melting point”
-Number of hydrogen bonds
-Hydrophilic groups (OH-, COO-, NH4+) > lipophilic groups (methyl, ethyl)
-Crystalline/amorphous properties

Question 12

What are some factors that need to be considered during the conversion of a weak acid to a salt ?

Answer 12

-chemical stability
- hygroscopicity
- manufacturability
- crystallinity may preclude the choice of a particular salt

Question 13

What are co-solvents ?

Answer 13

Co-solvents = liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs

Question 14

What are some commonly employed co-solvents ?

Answer 14

-Glycerol
-Ethanol
-Propylene glycol
-Poly(ethylene glycol)

Question 15

I where can Micellar solubilization increase the solubility of drugs ?

Answer 15

In the GI tract
(Drugs can be incorporated into or onto Micelles )

Question 16

What are cyclodextrins ?

Answer 16

Enzymatically modified starches composed of glucopyranose units which form a ring of either six (α-cyclodextrin), seven (β-cyclodextrin) or eight (γ-cyclodextrin) units

-normally one drug molecule will associate with one cyclodextrin molecule to form reversible complexes.

Question 17

What are the main purposes of excipients ?

Answer 17

Purposes:
- To facilitate the administration of the dosage form, e.g. pourability, palatability
- To protect the formulation from issues regarding physical and chemical stability and to enhance the solubility of the therapeutic agent

Question 18

What do buffers do as excipients and give some examples …

Answer 18

• To control the pH of the formulated product
• To maintain the solubility of the therapeutic agent in the formulated product
• To enhance the stability of products in which the chemical stability of the active agent is pH-dependent

Examples:
Acetates (acetic acid and sodium acetate)
Citrates (citric acid and sodium citrate)
Phosphates (sodium phosphate and disodium phosphate)

Question 19

When should sweetening agents as excipients be avoided ?

Answer 19

Avoid in oral formulations for children and patients with diabetes mellitus

Question 20

Why are sweetening agent excipients used in formulation ?

Answer 20

To increase the palatability of the therapeutic agent

Question 21

How are formulations containing viscosity-enhancing agents administered ?

Answer 21

-syringe
-small-metered cup
-traditional 5-ml spoon

(Viscosity-enhancing agents help it pour)

Question 22

What don’t require the specific addition of viscosity-enhancing agents ?

Answer 22

Syrups due to the inherit viscosity

Question 23

What do antioxidants excipients do for a formulation ?

Answer 23

They enhance the stability of the therapeutic agents that are susceptible to chemical degradation by oxidation.

Question 24

What are antioxidants and give an example …

Answer 24

• Molecules that exhibit higher oxidative potential than the therapeutic agent, to inhibit free radical-induced drug decomposition

Example ;
-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 25

What do chelating agents do in a formulation ?

Answer 25

They form complexes with the heavy metal ions involved in oxidative degradation of the therapeutic agent.

Question 26

What do preservative excipients do and what are some examples ?

Answer 26

They control the microbial bio burden of the formulation.

Examples:
Benzoic acid and salts
Sorbic acid and its salts
Alkyl esters of parahydroxybenzoic acid

Question 27

W

Question 28

What are the principle types of solution formulations administered orally ?

Answer 28

• Oral solutions
• Oral syrups
• Oral elixirs
• Linctus
• mouthwashes or gargles (for local effect)

Question 29

What is Lactulose oral solution used to treat and what does it consist of and produce ?

Answer 29

Treats ; Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients.

Consists of ;A synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose

Produces ; an osmotic diarrhoea because it is unabsorbed

Question 30

What are the excipients in lactulose oral solution ?

Answer 30

Excipient: Purified water (lactulose is water-soluble)

Question 31

What are the major components of an oral syrup ?

Answer 31

Major components:
- Purified water
- Sugar (sucrose) or sorbitol (non-sucrose base) or sugar substitutes (artificial sweeteners)
- sweetening agents
- viscosity-modifying agents
- preservatives

Question 32

What is an issue with cherry and orange flavoured oral syrups ?

Answer 32

• They are acidic
• This mean the solubility of these acidic drugs may be lowered causing precipitation.
• this reduces the chemical stability for acid-Kabila therapeutic agents.

Question 33

Who are medicated sugar-free syrups administered to ?

Answer 33

• children and diabetic patients.

-Sugar-free due to glycogenetic and cariogenic properties of sucrose.

-Syrup substitutes must provide equivalent sweetness, viscosity and preservation to the original syrups

-To achieve these properties ;
-Artificial sweeteners (typically saccharin sodium, aspartame)
-Non-glycogenetic viscosity modifiers (e.g. methylcellulose, hydroxyethylcellulose)
-Preservatives (e.g. sodium benzoate, benzoic acid and parahydroxybenzoate esters) are included.

Question 34

Give an example of an artificial sweetener …

Answer 34

Aspartame or saccharin sodium

Question 35

Give an example of a non-glycogenetic viscosity modifier ..

Answer 35

Methylcellulose or hydroxyethylcellulose

Question 36

Give an example of a preservative …

Answer 36

Sodium benzoate, benzoin acid and parahydroxybenzoate esters

Question 37

What is Bronchostop cough syrup traditionally used to treat ?

Answer 37

• traditional herbal medicinal product used for the relief of coughs ( chesty and dry )
• is sugar-free

Question 38

Give an example of an antioxidant (buffering agent) …

Answer 38

Citric acid monohydrate or ascorbic acid

Question 39

Give an example of a viscosity excipient …

Answer 39

Xanthan gum, acacia or Maltodextrin.

Question 40

What is an oral elixir and what is required to make sure all its components remain in solution ?

Answer 40

1) An elixir is a clear, hydroalcoholic solution for oral use

2) [Alcohol] required is sufficient to ensure all components remain in solution

Other polyol co-solvents may be incorporated

Question 41

What is a possible problem with an oral elixir when considering patient administration ?

Answer 41

A possible problem in paediatric formulations and adults who wish to avoid alcohol

Question 42

What are the typical components of oral elixirs ?

Answer 42

• purified water
• alcohol (co-solvent to ensure stability)
• polygon co-solvents (enables alcohol to be reduced and enhances stability)
• sweetening agents (high alcohol conc prohibits incorporation of high sucrose due to limiting solubility in this elixir vehicle)
• flavours and colours.

Question 43

What does a phenergan elixir contain and what does it treat ?
What does it treat for short term use ?

Answer 43

1) Contains ; promethazine (antihistamine)

2) Treatment: As symptomatic treatment for allergic conditions of the upper respiratory tract and skin including allergic rhinitis, urticaria and anaphylactic reactions to drugs and foreign proteins
(As an antiemetic)

3) For short term use ;
- Treatment of insomnia in adults
- Paediatric sedative

(An alcohol-free, sugar-free antihistamine formulation designed for use by children)

Question 44

Give an example of a sweetening agent …

Answer 44

Maltitol liquid and acesulfame potassium

Question 45

What is a linctuses and what is it primarily employed for the treatment of ?

Answer 45

1) Viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents.

2) Primarily employed for the treatment of cough, due to their soothing actions on the inflamed mucous membranes
(Can also be sugar-free)

Question 46

What is codeine linctus used to treat ?

Answer 46

• Indicated in adults for relief of the symptoms of dry or irritating coughs

Question 47

What is an example of a colourant flavouring …

Answer 47

• colourant = quinoline yellow, yellow dye sunset, caramel
• flavouring = lemon oil terpeneless, orange juice

Question 48

What are mouthwashes and gargles used to treat and what acts as the vehicle ?

Answer 48

1) treatment ; of infection and inflammation of the oral cavity
2 ) Water = vehicle
(Co-solvent may be employed to solubilise the active agent)