making a medicine

define a medicine

therapeutic agents used to treat or prevent disease

contains a drug and excipients (drug delivery system)

define a drug

chemicals that change physiological function in some way

active pharmaceutical ingredient (API)

define a formulation

the recipe for making a medicine, including ingredients and processes (of turning drug to medicine)

define an excipient

any ingredient that is not the drug (eg, a preservative)

added to drug to make the medicine

define dosage form

the physical form of the medicine (eg, tablet, capsule)

usually have different formulations for different dosage forms

define preformulation

the characterisation of the drug + excipients (eg, MW, logP, solublity)

what is the aim of formulation?

optimal drug delivery to the therapeutic target to maximise therapeutic efficacy and patient safety

what do local and systemic drug delivery mean?

local - applied to a specific part of the body

systemic - circulated all around the body

what is Lipinski’s rule of 5 for orally active drugs?

predicts how well a drug will be absorbed orally (based of its chemical structure)

• molecular weight <500

• logP <5

• H-bond donors <5

• H-bond acceptors <10

assumes absorption by passive diffusion

what is logP?

an indicator of lipophilicity

(how much a chemical ‘likes’ water or oil)

give the equation for logP

log (concentration in octanol/concentration in water)

what do logP values mean?

larger logP = more lipophilic

explain the importance of logP

determines permeability across biological membranes - affects absorption (and therefore efficacy and safety)

affects formulation decisions - solvent choice, dosage form (eg, emulsion vs suspension vs solution)

what is the Biopharmaceutics Classification System (BCS)?

a framework for grouping oral drugs by solubility and intestinal permeability based on empirical data

what is the purpose of the BCS?

facilitates formulation process/decisions

determines whether a drug will be absorbed well when given orally or not

drug must be absorbed to pass across a membrane - cannot be too lipophilic (won’t dissolve in cytoplasm) or hydrophilic (won’t cross phospholipid bilayer)

what is solubility?

the maximum amount of a substance (solute) that can be dissolved in a given medium (solvent)

list some properties that influence solubility

solvent properties (eg, polarity, pH)

solute properties (eg, solid form, pKa)

temperature and pressure

why is solubility important?

it affects drug dissolution and absorption

is a key factor that determines oral bioavailability (ie, BCS)

underpins formulation decisions (eg, excipient choice)

many drugs that are poorly water soluble may have increased solubility and absorption in fatty intestinal environment (eg, after a meal)

what is the purpose of preformulation?

determines physiochemical properties of the drug

informs decisions about the best formulation strategy