Oral Drug Delivery III: Formulation Factors and Excipients

ORAL DRUG DELIVERY III

OUTLINE

• Objective:
    - Describe how formulation factors impact drug performance.
    - Apply knowledge of formulation principles to predict how changes in dosage form may alter bioavailability.

EXCIPIENTS IN DRUG FORMULATION

• Definition:
    - Excipients are non-active ingredients added to a formulation to assist with preparation, improve patient acceptability, and enhance the performance of the dosage form as a drug delivery system.

• Types of Excipients:
    - Diluents
    - Surfactants
    - Lubricants
    - Disintegrants
    - Viscosity-enhancing agents

FORMULATION FACTORS

• Dosage Forms:
    - Composed of Active Ingredients (Drugs) + Other Substances (Excipients)

DILUENTS

• Function:
    - To increase the bulk of potent drug substances.

• Examples:
    - Lactose
    - Sucrose
    - Glucose
    - Mannitol
    - Sorbitol
    - Calcium Phosphate

• Case Study:
    - In Australia, in 1960, the toxicity of phenytoin was increased when its excipient was changed from calcium sulphate to lactose.
      - Impact:
        - Lactose led to an increase in the bioavailability of the active drug       - Calcium sulphate decreased gastrointestinal absorption of phenytoin by forming a poorly soluble calcium-phenytoin complex.

• Mnemonic:
    - "Why do diluents make great friends? Because they always help you fill the gaps!"

SURFACTANTS

• Composition:
    - Hydrophilic (water-loving) head
    - Hydrophobic (water-hating) tail

• Functions:
    - Emulsifying agent
    - Solubilizing agent
    - Suspension stabilizer

• Mechanism:
    - Stabilize oil-water mixtures
    - Enhance solubility of hydrophobic drugs
    - Prevent settling or aggregation of particles

• Examples:
    - Sodium Lauryl Sulfate
    - Lecithin
    - Polysorbate 80

• Wetting Agents:
    - Improve spreading of liquids on solid surfaces
      - Examples: Sodium Lauryl Sulfate, Cetyl alcohol

LUBRICANTS

• Function:
    - To reduce friction between powder and metal surfaces during manufacturing.

• Examples:
    - Magnesium stearate
    - Stearic acid
    - Polyethylene glycol
    - Sodium lauryl sulfate
    - Sodium stearyl fumarate
    - Liquid paraffin

DISINTEGRANTS

• Function:
    - To break up capsules, tablets, and granules into primary powder particles, thus increasing the effective surface area of the drug.

• Examples:
    - Starch
    - Cellulose
    - Crosslinked Polyvinyl Pyrrolidone
    - Sodium Starch Glycolate
    - Sodium Carboxymethyl Cellulose

• Mnemonic:
    - "Why are disintegrants great friends? Because they always help you break the ice… and the tablet!"

VISCOSITY-ENHANCING AGENTS

• Function:
    - Control ease of pouring
    - Control rate of sedimentation of dispersed particles (suspensions)

• Examples:
    - Suspending agents and thickeners, e.g., Xanthan gum, Hydroxypropyl Methylcellulose
    - Viscosity modifiers, e.g., Glycerin, Propylene glycol

SUMMARY

• Moral of the Story:
    - The Active Pharmaceutical Ingredient (API) receives the credit, but the excipients make it work.