SL12102

LECTURE 4: ROLE OF DOSAGE FORMS AND EXCIPIENTS

1. Why are drugs not administered as pure substances?

- They need to be formulated into a dosage form with the same API.

2. Dosage forms:
Dosage form= the means by which drug molecules are delivered to sites of action within the body.
- Dosage forms have physical form as either a solid, semisolid or a liquid and have a specific route of
administration.

3. What is needed in a dosage form?

a) Accurate dosing.
b) Protection and shelf life.
c) Protection from gastric juice.
d) Masking of taste and odor.
e) Placement of drugs directly within body tissues.
f) Sustained release medication.
g) Controlled release medication.
h) Insertion of drugs into body cavities.
i) Use of desired vehicle for insoluble drugs.

4. What is an excipient?
Excipient = all the other compounds of a formulation other than the active drug.
- Each component requires evaluation for safety, an excipient should be chemically and physiologically inert.

5. Uses for excipients:

- Aids processing of the system during manufacture and accurate dose control.
- Controls the rate of absorption.
- Protect, support or enhance stability, bioavailability or acceptability.
- Assists in product identification.
- Enhances other attributes of overall drug safety and the overall effectiveness of the drug protucy during storage
and use.

6. Dose control:
- Drugs are formulated to control dose.
 - Some drugs have higher doses (difficult for patient to measure) or lower doses (difficult to manufacture and blend
uniformly).
- High dose but low potency drugs can be a problem to formulate, takes too many to get desired effect.
- If the drug has poor floe/compressibility it cannot make a tablet.

7. Why are some tablets coated?

- To mask the bitter taste.
- To avoid gastric mucosal irritation that may lead to ulcers/bleeding etc.

8. Solid dosage forms:

Tablet = hard, compressed medication in round, oval or square shape.
- Excipients include diluents/binder/glidants/dry lubricants to ensure efficient tableting, disintegrants to ensure the
tablet breaks up in the GI tract and sweeteners/film coating to mask taste of API.
- 90% of tablets are taken orally.
Requirements for ideal oral solid dosage form:
1. Drug must remain stable.
2. Drug must be bioavailable (formulation reliably releases drug in GI tract).
3. Uniform drug content (reproducible dose).
4. Robust and resilient to disintegration during handling.
5. Easy and cost effective to produce.
6. Pleasant to take.

9. Types of solid drug forms:

- Buccal and sublingual medications:
a) Administered by placing in mouth under tongue or between gum and cheek.
b) Medication dissolves rapidly and absorbed through mucous membranes of the cheek and enters
bloodstream.
c) Bypasses the stomach and liver.
- Effervescent tablet:
a) Uncoated tablets that typically contain acid substances and bicarbonates which react rapidly in the presence
of water to effervesce by releasing CO2.
b) Very rapid tablet dispersion and dissolution.
c) Pleasant tasting (addition of sweetener).
d) Lubricants need to be water soluble.
e) Tablet packaging is critical for stability.
- Capsule.
 a) Drug formulation is contained in a gelatin of Hydroxypropyl methylcellulose matrix.
b) Masks the unpleasant taste of its contents.
c) Hard shelled capsules = used for dry powdered ingredients.
d) Soft shelled capsules = primarily used for oils for API dissolved or suspended in oils and emulsion.
- Oral granules.
a) Solid, dry-aggregates of powder particles.
b) Soft granules placed on tongue and swallowed with water or dissolved in water.
- Oro-dispersible tablets.
a) Dissolves rapidly in oral cavity resulting in solution or suspension without needing water.
b) Tablet disperses in saliva, some absorbed un mouth, some saliva passes towards the stomach (potentially
increasing bioavailability).
c) Formulations are either very porous/soft molded matrices or compressed into tablets with very low
compression force.
d) Tablets are difficult to handle and require specialized packaging.

10. Liquid dosage forms:

- Solutions:
a) Clear liquid preparations for oral use.
b) Contains one or more APIs dissolved in a solvent (diluted alcohol, glycerin, propylene glycol/purified water).
- Emulsions =
a) Stabilized oil-in-water dispersions, either or both phases of which may be dissolved in water.
- Suspensions =
a) Liquid preparations for oral use containing one or more APIs suspended in a suitable vehicle (purified water
with cellulose derivative polymers and thickening agents).
- Syrup =
a) Concentrated aqueous solution of a sugar.
b) Flavoured syrups are a convenient form for bad tasting drugs.
- Elixir =
a) Pleasantly flavoured clear liquid oral preparation of potent or nauseous drugs.
b) May contain high proportion of ethanol in purified water and sucrose together w/ antimicrobial preservatives
which confers the stability of the preparation.
- Linctus =
a) Viscous, liquid oral preparation that are usually prescribed for the relief of cough.
b) Small dose volume.
c) High proportion of syrup and glycerol which have an anti-inflammatory (demulcent) effect on the membranes
of the throat.
- Oral drops =
 a) Liquid preparations for oral use to be administered in small volumes with the aid of suitable measuring device.

11. Semi-solid dosage forms:

- Ointments =
a) Viscous, semi-solid, greasy preparations (80% oil to 20% water) for application to skin, rectum or nasal
mucosa.
b) Base is typically anhydrous and immiscible with skin.
c) May be used as an emollient (creates occlusive barrier) or to apple suspended or dissolved medicaments to
the skin.
- Creams =
a) Semi-solid emulsion, mix of oil and water.
b) Oil in water creams (O/W) = more comfortable and cosmetically acceptable as they are less greasy.
c) Water in oil creams (W/O) = difficult to handle, however, many drugs incorporated in creams are hydrophobic
and released more readily from water in oil creams. More moisturizing as they create an oily barrier that
reduces water loss from the stratum corneum.
- Gels =
a) Semi-solid system in which a liquid phase is constrained within a 3D polymeric matrix (consisting of a
polymer) having a high degree of physical or chemical cross linking.
b) Used for medication, lubrication and as a carrier for spermicide.
- Transdermal patch =
a) Medicated adhesive path placed on skin to deliver a specific dose of medication through the skin and into the
bloodstream.
b) Provides controlled release of the medicament into the patient.
- Suppositories/pessaries =
a) Solid dosage forms intended for administration of medicine via the rectum, vagina (pessaries) or urethra
(bougies) that melt, soften or dissolve in the body cavity.
b) Made by dissolving or dispersing the APIs in a base at an elevated temperature, poured into a mould and
solidified at room temperature.

12. Other dosage forms:

- Parenteral =
a) An injection (infusion method) of putting liquid into the body with a hollow needle and syringe that is pierced
to a sufficient depth and forced into the body.
IV = liquid administered directly into the bloodstream vein. 100% bioavailability. Advantageous for rapid onset
of action.
Intramuscular = injection of a substance directly into the muscle (eg. vaccines). Dependent on chemical
properties, can be absorbed quickly or more gradually.
Subcutaneous = injecting fluid into the subcutis. Highly effective in administering vaccines and insulin.
- Inhaled =
a) Administered by the nasal or oral respiratory tract.
b) Either solutions, suspensions or dry powder formulation.

- Ophthalmic =
a) Saline containing eye drops used as a vehicle to administer medication into the eye.
b) May contain steroids, antihistamines or topical anaesthetics.
c) Some do not have medication and are only lubricating.
d) Can also be in the form of an ointment (application to the conjunctiva).
- Otic =
a) Solutions, suspensions or emulsions of drugs that are instilled into the ear with a dropper.
b) Used to treat/prevent ear infections.