Dosage Forms

Question 1

Sublingual & Buccal

Answer 1

Sublingual - under the tongue.
Buccal - between the gum & the cheek.
Rapidly dissolve & absorbed rapidly through the mucous membranes, where they enter the bloodstream, bypassing the stomach & liver.

Question 2

Effervescent Tablet

Answer 2

• Uncoated tablets which effervesce in water before consumption.
• Gives rapid tablet dispersion & dissolution, can be pleasant taste & lubricants need to be water soluble.
• Use sodium bicarbonate to produce effervescence.
• Sodium bicarbonate can increase rate of tablet disintegration, dissolution & gastric emptying, enabling faster absorption speed.

Question 3

Oral Granules

Answer 3

Solid, dry aggregates of powder particles oft in sachets. Some swallowed, some with water.

Question 4

Suppositories

Answer 4

Via rectum, vagina (pessaries) or urethra (bougies) that melt, soften or dissolve in the body cavity. Useful for targeted or avoiding hepatic first pass.

Question 5

Oro-dispersible tablets/melts

Answer 5

Dissolves or disintegrates in saliva, making solution or suspension. May be absorbed in mouth, pharynx & oesophagus, possibly increasing bioavailability.

Question 6

Capsules

Answer 6

Drug within a gelatine or a sugar-based matrix:
1. Hard-shelled capsules, which are normally used for dry, powdered ingredients,
2. Soft-shelled capsules, primarily used for oils & for APIs dissolved or suspended in oils or emulsions.

Question 7

Solution: Adv & Dis

Answer 7

Clear liquid preparations for oral use containing APIs dissolved in a solvent.
Adv:
* delivery system for low solubility drugs
* avoid large vol of solvent- solution of this drug
* avoid precipitation upon storage when co-solvent is used
* taste masking of drugs
* difficulty in swallowing solid-dosage forms
* controlled drug delivery
Dis:
* Problems - correct dosage
* unstable; formulation to ensure stability over the period of the shelf-life
* difficult aesthetic suspension
* bulky, difficult for patient to carry

Question 8

Emulsions

Answer 8

Oral emulsions are stabilized oil-in-water dispersions, either or both phases of which may contain dissolved solids.
Adv:
* Delivery of drugs with low (aq) solubility:
* Taste masking - sweetening agents
* Administration of oils with therapeutic effect
* reduction of irritation after topical administration: drug in internal phase (o/w)
* ease of swallowing
* total parenteral nutrition
Dis:
* Thermodynamically unstable; appropriate formulation is needed to stabilise the emulsion from separation of the two phases.
* Pharmaceutical emulsions may be difficult to manufacture.

Question 9

Suspensions

Answer 9

One or more APIs suspended in a suitable vehicle, possibly altered with thickening agents.

Question 10

Syrup

Answer 10

• [Highly] (aq) of sugar or substitute & flavouring agent - masks bad taste
• unflavoured syrup, mostly sugar
• drugs: directly incorporated or added as the syrup is being prepared
• choice of syrup vehicle based on physicochemical properties of drug

Question 11

Elixir

Answer 11

Pleasantly flavoured clear liquid of potent or nauseous drugs. Antimicrobials & ethanol within purified water used to confer stability of the preparation.

Question 12

Linctus

Answer 12

Viscous, liquid usually prescribed for the relief of cough, & reduces inflammation of throat, typically small dose.

Question 13

Ointments

Answer 13

Viscous, semi-solid, greasy preparations for application to the skin, rectum or nasal mucosa. Ointments may be used as emollients or to apply suspended or dissolved medicaments to the skin.

Question 14

Transdermal Patch

Answer 14

Deliver specific dose through the skin & into the bloodstream in a controlled release.

Question 15

Creams

Answer 15

Semi-solid emulsions, which are mixes of oil & water. Divided into two types:
1. Oil-in-water (O/W) creams: less greasy & more easily washed off using water.
2. Water-in-oil (W/O) creams: used many hydrophobic drugs & will be released more readily from a water-in-oil. Are also moisturizing.

Question 16

Subcutaneous

Answer 16

Injecting fluid into the subcutis, the layer of fatty tissue directly below the dermis & epidermis. Highly effective in administering vaccines & such medications as insulin.

Question 17

Intramuscular Injection

Answer 17

Injection of a substance directly into a muscle. Can be faster or more gradual.

Question 18

Intravenous (IV) injection

Answer 18

Injected in a vein with 100% bioavailability for rapid action.

Question 19

Preformulation

Answer 19

1st step in developing dosage forms using the physiochemical properties of the API

Question 20

Subcutaneous: Adv & Dis

Answer 20

Advantages:
* Slow, sustained delivery
* Self-administration possible
* Implants for long-term delivery
Disadvantages:
* Small doses
* Pain and irritation from repeated injections

Question 21

Intramuscular drug delivery: Adv & Dis

Answer 21

Advantages:
* Relatively large volume
* Sustained release
Disadvantages:
* Professional required
* Erratic absorption

Question 22

Intravenous drug delivery: Adv & Dis

Answer 22

Advantages:
* Rapid effects
* Dose – precise dosing, large volumes possible
* 100% bioavailability
Disadvantages:
* Potential toxicity – rapid Cp elevation (can be controlled by infusion)
* Suitable vein
* Professional required – admin. & monitoring
* Cost
* Duration (infusion can extend dosing)

Question 23

Sublingual & Buccal: Adv & Dis

Answer 23

Advantages
- Possible Hepatic first pass avoidance
- Residence time – sustained delivery possible
- Taste
- Good Compliance – talking, eating, drinking, etc
- Rapid action
Disadvantages
- Irritation – possible, but oral mucosa robust

Question 24

Suppositories: Adv & Dis

Answer 24

Suppositories
Adv:
- good for unconscious or vomiting patients
- avoids poor taste
- Avoidance of possible upper GI tract disease
- Drugs extensively degraded via oral delivery
- Sustained release possible
- Possible protein delivery
Dis:
- compliance

Question 25

Tablets: Adv & Dis

Answer 25

Adv:
* Accurate dosage/ minimum variability
* Convenience
* Greater stability than liquid
* Tailored rate of release
* Mass production
* Simple & cost effective
* Good Compliance
Dis:
* Swallowing
* Difficulty in preparing some formulations
* Bitter taste &/or bad odour
* Oxygen & moisture sensitivity requiring coating of certain tablets

Question 26

Capsules: Adv & Dis

Answer 26

Adv:
* No need to compress drugs
* Drug uniformity
* Dispersed drug stability - oily vehicle protects drugs sensitive to oxidation or hydrolysis.
* Drug formulations as self-emulsifying oils increases oral bioavailability.
Dis:
* Drugs containing high [water] or other gelatine solvents can’t be incorporated.
* Surfactants affect the capsule seal
* Needs specific pH range
* Crosslinking: Gelatine crosslinking may render capsule insoluble.
* Water loss or uptake may damage capsule

Question 27

Tablet production requirements:

Answer 27

1) Particles must be sufficiently free flowing
2) Particles, when subjected to a force, cohere to form a compact of adequate strength
3) Adhesion of the tablet must be avoided
Few API meet this list, so excipients are ergo required.

Question 28

Liquid Dosage forms: Adv & Dis

Answer 28

Adv:
* Better compliance
* Faster therapeutic response
* Homogeneous system
* Reduced irritation; immediate dilution by gastric contents
Dis:
* Breakage of container
* Growth of microorganism
* Poorer stability in (aq) than solid dosage form. Stability of excipients.
* Shorter shelf-live than solid dosage form.
* Dose accuracy (patients uses spoon)
* unsuitable for drugs chemically unstable in presence of water

Question 29

Liquid solution Vehicle: Purified Water USP:

Answer 29

Liquid solution Vehicle: Purified Water USP:
* Low cost & toxicity
* Tap water has chemical incompatibilities
* Solid residue after evaporation high
* Unsuitable for parenteral formulations as not sterilised

Question 30

Oral administration: Adv & Dis

Answer 30

Adv:
* GI tract designed for absorption
* Easier, no infection risks
* Broad diversity of oral dosage forms
* Able to do a variety of release times
* Compliance
Dis:
* Hepatic first pass
* Difficulty swallowing
* Possible Drug Degradation

Question 31

Nasal drug delivery: Adv & Dis

Answer 31

Adv:
- Topical delivery for treatment
- Avoidance of first-pass metabolism
- Good for Drugs sensitive to intestinal metabolism e.g. Acid-sensitive drugs
- Good for Polar compounds with poor oral absorption
- Small, lipophilic drugs can diffuse through the nasal epithelium & enter circulation with up to 100% bioavailability.
- Ease of administration (drops and sprays)
- Little blood brain barrier, drugs enter brain through paracellular diffusion or through olfactory nerves. Promising for drug delivery to CNS
Dis:
- Nasal physiology differences make absorption inconsistent
- Mucus acts as a physical & chemical barrier to drug diffusion.

Question 32

Vaginal Drug Delivery: Adv & Dis

Answer 32

Adv:
- Topical delivery
- Avoidance of hepatic – first pass effect.
- Area has lower enzyme activity
Dis:
- Many physiochemical factors vary with age and cycle.

Question 33

Ocular drug delivery:

Answer 33

Drugs administered solely for treatment of local conditions, not a viable route for systemic delivery

Question 34

Transdermal Delivery: Adv & Dis
Things to increase skin permeability

Answer 34

Adv:
- Hydration of Stratum Corneum increase permeability
- Control delivery of potent drugs
- Reduced dosing frequency
- Fewer side-effects are possible
- Can be stopped at any time
- Good compliance
- Hepatic first pass avoidance
- Injury & disease reduce barrier action
Dis:
- Cutaneous first-pass
- Varies with age
- Varied thickness of skin

Things to increase skin permeability:
- Iontophoresis – provides active drug reservoir for release
- Microneedles – attach to epidermis, then releases substances into it

Question 35

Pulmonary drug delivery: Adv & Dis

Answer 35

Adv:
- Topical delivery
- Huge potential for systemic delivery
- Avoids hepatic first-pass
- Reduces dose needed, minimizing side effects
Dis:
- Large SA, rapid administration possible
- Mucus acts a chemical & physical barrier

Question 36

Multi particulate Systems: Adv & Dis

Answer 36

Adv of multi-particulates:
* More consistent GI transit than single dose monolithic tablet.
* Good stability, flow & bulk density
Dis:
* Control of membrane characteristics using film-coating can be difficult.
* Multi-particulates are difficult to retain in the upper GI tract.
Drug-release mechanisms from multi-particulates:
* Diffusion: Water diffuses in, the drug dissolves & diffuses across controlled-release coat.
* Osmosis: Water enters, osmotic pressure builds, forcing drug solution out.
* Erosion: Coating degrades over time, releasing the drug.

Question 37

Water soluble: Adv & Dis (relative to fatty bases):

Answer 37

Adv
* Suppository m.pt. can be adjustable to withstand exposure to warmer temp.
* Release of drug is independent upon m.pt.
* Physical stability on storage is improved.
* Suppositories are readily miscible with rectal fluids.
Dis:
* Chemically more reactive than fats. Incompatible with many drugs.
* Care required in processing to avoid inelegant contraction holes in the suppositories.
* Greater MW PEG slows release rate.
* PEGs tend to be more irritating to mucous membranes than fatty bases.

Question 38

Parenteral Continuous infusion: Adv & Dis

Answer 38

The drug is added to a large volume of parenteral fluid, which is slowly & continuously administered into a vein
Adv:
* Drug plasma levels are easily controlled by adjusting the infusion rate
* Constant drug plasma levels can be achieved
* Less problems of irritation/toxicity
Dis:
* Continuous monitoring
* Solubility & stability of some drugs
* Fluid-restricted patients