Oral solution dosage forms

Question 1

What are some common forms of pharmaceutical solutions?

Answer 1

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

Question 2

What are two downsides to pharmaceutical solutions?

Answer 2

• Rate of absorption can be limited by precipitation
• Chemical stability is lowest in solutions

Question 3

What is a pharmaceutical solution?

Answer 3

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

Question 4

What are some common liquid oral solution forms? + why so used?

Answer 4

• Drugs are commonly given in solution
• in cough/cold remedies
• for the young and elderly (people with Parkinson’s)
• Absorption from an oral solution is often rapid and complete, skip one step compared to tablets, greater bioavailability compared to other oral dosage forms

Question 5

What are the advantages to pharmaceutical oral solutions?

Answer 5

• 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 6

What are the disadvantages to pharmaceutical oral solutions?

Answer 6

• 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 7

What are some examples of co-solvent excipients?

Answer 7

Ethanol, glycerol, propylene glycol

Question 8

What are some examples of antioxidants excipients?

Answer 8

Sodium metabisulphite, ascorbic acid

Question 9

What are some examples of antimicrobial preservatives excipients?

Answer 9

Benzalkonium chloride, parabens, potassium sorbate

Question 10

What are some examples of pH adjusters excipients?

Answer 10

Citric acid, potassium phosphate

Question 11

What are some examples of Isotonicity adjusters excipients?

Answer 11

Sodium chloride, glucose

Question 12

What are some examples of viscosity enhancers excipients?

Answer 12

Hydroxymethylcellulose

Question 13

What are some examples of chelating agents excipients?

Answer 13

EDTA

Question 14

What are some examples of flavours excipients?

Answer 14

Taste masking

Question 15

What are some examples of sweeteners excipients?

Answer 15

Sucrose, sorbitol, mannitol, aspartame, sucralose

Question 16

What are some examples of colouring agents excipients?

Answer 16

Dyes

Question 17

What type of water is used in pharm sols?

Answer 17

Tap drinking water not normally used for the manufacture of pharmaceutical solutions /extemporaneous compounding

Question 18

If tap water is used/ water what type of processes must it go through to be used?

Answer 18

• Purified by distillation, ion exchange, or reverse
  osmosis → non-parenteral solutions
• Further purified to remove pyrogens (fever-
  producing compounds) → water for injections

Question 19

What is a challenge in drug solubility?

Answer 19

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

Question 20

What happens when drug solubility high?

Answer 20

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

Question 21

What happens when drug solubility is moderate?

Answer 21

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

Question 22

What happens when drug solubility is low?

Answer 22

• Formulated as an alternative-dosage form, e.g. a suspension, emulsion biphasic

Question 23

What needs to happen in drug dissolution between therapeutic agent and water?

Answer 23

• Removal of a molecule of the drug from the solid state
• Formation of a cavity within the solvent
• Accommodation of the drug molecule into the formed cavity.

Question 24

What factors affect the solubility of therapeutic agents?

Answer 24

*physicochemical properties
*big molecular weight (not likely to dissolve)
*big particle size (not likely to dissolve)
* solubility ∞1/melting point
*number of hydrogen bonds
*not many hydrophilic groups (not likely to dissolve)
* mostly crystalline (not likely to dissolve) / amorphous properties

Question 25

pH and pka in terms of solubility for acids and bases?

Answer 25

acids: pH > pKa = solubility increases bases: pH < pKa = solubility increases

Question 26

What is the acceptable range for pH in oral solutions?

Answer 26

pH 5 - 8 cannot go below or above + can be adjusted using a buffer as long as its in the safe pH

Question 27

What is another way to increase pH?

Answer 27

converting weak acids into a salt

Question 28

Why can we not always change weak acids into salts?

Answer 28

*chemical stability, hygroscopicity, manufacturability and crystallinity may preclude the choice of a particular salt *The sodium salt of aspirin, sodium acetylsalicylate, is much more prone to hydrolysis (phenolic ester bond) than aspirin (acetylsalicylic acid)

Question 29

What is a co-solvent?

Answer 29

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

Question 30

What are commonly used co-solvents?

Answer 30

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

Question 31

What are some properties of glycerol and propylene glycol?

Answer 31

* Odourless, sweet, viscous

Question 32

What are some properties of ethanol?

Answer 32

* Known pharmacological and toxicological effects have compromised use

Question 33

What are some properties of PEG?

Answer 33

* Lower-molecular-weight grades (PEG 200, PEG 400) are preferred

Question 34

What is a cyclodextrin?

Answer 34

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

Question 35

Why are cyclodectrin used?

Answer 35

* The ring of β-cyclodextrin is the correct size for most drug molecules, and normally one drug molecule will associate with one cyclodextrin molecule to form reversible complexes

Question 36

What are the purposes of excipients?

Answer 36

* 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 *physiologically inert

Question 37

What is the purpose of buffers?

Answer 37

* 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

Question 38

What are some examples of buffers?

Answer 38

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

Question 39

What is the purpose of sweetening agents?

Answer 39

* To increase the palatability of the therapeutic agent * Main sweetening agents * Sucrose, liquid glucose, glycerol, sorbitol * Artificial sweetening agents is increasing in use *avoid in oral formulations for children and patients with diabetes mellitus

Question 40

What is the purpose of flavouring agents? +examples of flavours

Answer 40

* To mask the taste of the drug substance * Salty: butterscotch, apricot, peach, vanilla, wintergreen mint * Bitter: cherry, mint, anise * Sweet: vanilla, fruit, berry * Sour: citrus, raspberry * Usually a combination to achieve the optimal taste-masking

Question 41

What else is in flavouring agents?

Answer 41

*methanol, chloroform to numb your taste buds to stop you from tasting the drugs

Question 42

What is the purpose of viscosity agents?

Answer 42

* To ensure the accurate measurement of the volume to be dispensed * May increase palatability

Question 43

How are viscosity agents administered and controlled?

Answer 43

* Administration performed using a * Syringe * Small-metered cup * Traditional 5-ml spoon * Increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers

Question 44

What is an antioxidant?

Answer 44

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

Question 45

What is the purpose of antioxidants + examples?

Answer 45

* To enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation - aqueous - oil based

Question 46

What is the purpose of chelating agents?

Answer 46

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

Question 47

What is the purpose and properties of preservatives?

Answer 47

* 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