Concepts of bioavailability

What is a drug?

Substance that affects the structure or functioning of a living organism

Used for the prevention, diagnosis or treatment of disease or for the relief of symptoms

What is a medicine?

Drug delivery system

Used to administer drug to the body efficiently, safely, reproducibly and conveniently

What is a formulation?

Drug substance converted with excipients into a patient acceptable product

• Makes a dosage form

What are the different dosage forms?

Liquids: 

• Solutions (mixtures, linctuses, gargles, lotions), suspensions, emulsions

Solids:

• Powders, granules, capsules, tablets, suppositories, pessaries

Semi-solids: 

• Creams, ointments, gels, pastes

What is the therapeutic outcome of a drug is dependent on?

1. adequate concentration of drug reaching the site of action/target

• Too high = overdose

• Too little = no effect

2. drug concentration maintained for the required amount of time

What is drug concentration in the blood depends on?

• Relative amount of an administered dose reaching the systemic circulation

• Rate at which drug reaches systemic circulation

• Rate and extent of distribution of drug from systemic circulation to tissues and target site

• Rate of drug elimination from the body

Where does dynamic equilibrium happen for systemically acting drugs?

Exists between drug concentration at the site of action and concentration of drug in blood plasma

What's different about the type of blood plasma dynamic equilibrium exists between with systemic drugs?

It is plasma water so protein free

What part of the blood do drugs have to be dissolved in to be effective?

Drugs that are dissolved in plasma water can pass through the capillary endothelium and reach site of action

Why is measuring drug concentration at the target site complicated and how is it measured?

Drug conc in blood might not show accurately the conc at the target

• Drug may bind to blood cells and plasma proteins

Clinically drug conc in plasma = drug conc at site of action

What is bioavailability?

The relative amount of an administered dose of a drug which reaches systemic circulation in a given time and the rate at which this occurs

What is the bioavailable dose?

The fraction of an administered dose of drug that reaches the systemic circulation in unchanged form

What is bioavailabilit important for?

Important in determining if a therapeutically effective concentration of the drug is achieved at the target site

What are the stages of oral delivery?

1. Drug must be completely released from the dosage form into solution in the gastro intestinal fluids

   • Drug must exhibit sufficient solubility in polar media

   • Drug must be stable in gastrointestinal fluids

2. Drug must then cross the gastro intestinal barrier into mesenteric circulation

   • Only drugs which exhibit a good balance between hydrophilicity and lipophilicity are absorbed

3. Finally, drug must pass into systemic circulation without being metabolised in the liver

What factors alter the rate and extent of absorptions?

What is disintegration?

Rate of solubilism in a given time

What factors influence oral bioavailability?

1. Food

2. Age of the patient

3. Physico-chemical properties of the drug such as solubility, log P

4. Type of dosage form ( solids compared to liquids)

5. Composition of the dosage form (immediate release tablet versus sustained release)

6. Salt form of the drug (ibuprofen sodium when compared to ibuprofen lysinate)

   • Made to overcome solubility

What are the different paths of absorption?

Paracellular:

• Passive

• Very low molecular weight drugs pass through

• Depends on drug properties

• Lipid like membrane filter

 Transcellular:

• Diffusion

• Hydrophobic drug particles

• Conc dependent, pH and ionisation state

 

How do drugs get transported through cells?

• Carrier-mediated system

• Like a transporter pump

• Requires energy (ATP)

• Enzyme-therefore prone to saturation

• System can exist in uptake (in) or efflux (out) state

• Drug-drug interactions can compete for transporter

• Specific transporters exist for endogenous substances in the body

What is the oral mucosa?

 First site of absorption encountered in oral delivery

• Found at five sites in the cavity: buccal, sublingual, palatal, labial, and gingival

• Buccal and sublingual are the most permeable so the main targets for drug delivery

What is the oral mucosa divided into?

Subdivided into three types: lining mucosa, specialised mucosa, and masticatory mucosa (determined by location and historical properties)

• Mucosa is highly vascularised, allowing for both mucosal (local) and transmucosal (systemic) effect