Properties of Medicines PDF

L12 Turning a drug into a medicine Turing a Drug into a Medicine Prof Stuart Jones King’s College London Drug = active compound Medicine = other chemicals and device needed to get the drug to work.  Properties of Med...

L12 Turning a drug into a medicine Turing a Drug into a Medicine Prof Stuart Jones King’s College London Drug = active compound Medicine = other chemicals and device needed to get the drug to work.  Properties of Medicines Outline Medicine Development Medicines Design Chemical and Physical Properties Routes of Delivery Medicine Quality Properties of Medicines Learning Objectives - Revise the process of medicine development - Learn to differentiate between physical and chemical properties - Learn how physical and chemical properties can inform medicines design - Learn how routes of delivery inform medicines design - Learn how to use the medicine design to assess medicine quality 2  Properties of Medicines Medicine Development When is the drug made into a medicine? The MEDICINE is developed between lead optimisation and preclinical development. 3  Properties of Medicines Medicine Design (TPP) TPP = target product profile TPP sets criteria for the medicine’s design. 4  Properties of Medicines Medicine Design 1. A drug has certain intrinsic behaviours (physical chemical properties) 2. A formulation holds the drug to make a medicine and either conserves the drug’s behaviours or adapts them (e.g. delivery routes) 3. A medicine must store the drug and maintain high quality 1. Chemical structure needed to understand the properties of the molecule. E.g. is it big, small, functional groups. 5  Properties of Medicines Chemical and Physical Properties Physical properties: ‘can be observed or measured without changing the composition of matter. Physical properties are used to observe and describe matter.’ E.g. temperature, refractive index, density, and hardness of an object Big = bigger than 500-1000Da Properties of Medicines Chemical and Physical Properties Chemical properties: ‘describes its "potential" to undergo some chemical change or reaction by virtue of its composition. What elements, electrons, and bonding are present to give the potential for chemical change.’ E.g. Corrosion of metals resulting in metal oxides 6  Properties of Medicines Chemical and Physical Properties Properties of Medicines Chemical and Physical Properties Physical properties of diclofenac Which properties are physical properties and which are chemical properties ? Software can tell you the above information. 7  Does the drug dissolve? (This would affect concentration). LogP = partition coefficient – lipid solubility high – partitions into membrane easily. PKa = ionization constant – is the drug dissolvable Properties of Medicines - Student Activity (intrinsic drug behaviour) Chemical Functional Behaviour Properties Characteristics 8  Properties of Medicines - Intrinsic drug behaviour Activity - Classify Log P PKa Ionisation Chemical Dissolution rate Good chemical Elemental reactivity composition stability Low Diffusivity Solubility Melting point Molecular weight Chemical High Structure permeability Horrible Taste Chemical Properties Functional Characteristics Behaviour Chemical Properties o PKa o Elemental compos o Log P Functional Characteristics o Ionisation o Molecular weight o Dissolution rate Behaviour o Good chemical stability o Chemical reactivity o Low solubility o Diffusivity Behaviour always linked to the chemical structure. 9  Properties of Medicines Routes of Delivery Formulation design: priority = appropriate formulation and conserve activity of the drug. 10  Properties of Medicines Routes of Delivery Pharmacokinetics accounts for 40% of drug failures. Pharmacokinetics can be changed by the formulation. 11  Properties of Medicines Routes of Delivery PK changes depending on route of delivery Properties of Medicines Oral Route Buccal/sublingual (from the buccal cavity or under the tongue) Oral (after swallowing) Rectal (administered into the rectum) 12  Properties of Medicines Buccal Route Buccal ROA intended either for sustained local delivery or rapid/enhanced systemic delivery commonly a small (hard) tablet which is held in the mouth (often below the lip) to achieve a sustained release of the drug or a rapidly disintegrating drug tablet held under the tongue (sub-lingual), used for rapid/enhanced systemic absorption, eg nitroglycerin for the rapid relief of angina Properties of Medicines Inhaled Route Systemic or local delivery Attractive target for systemic drug absorption because of its large surface area (approximately 140 m2 – an area of a tennis court) ‘Upside down tree’ – like structure 13  Properties of Medicines Nasal Route The nasal cavity has a volume of 15 to 20 cm3 and a surface area of 150 to 180 cm2 Each cavity consists of three regions: 1) vestibules 2)respiratory region, consisting of turbinates or chonchae, and 3) olfactory region http://www.harvard-wm.org/human-nose-body/anatomy-of-the-nasal-cavity- showing-the-nasopharynx/ Properties of Medicines Dermal Route The major barrier to drug permeation is stratum corneum - the outermost skin layer Image taken from: http://www.nature.com/nrg/journal/v3/n3/images/nrg758-f1.jpg 14  Slows down PK but acts as a good barrier and only lets certain compounds in. Properties of Medicines Route – Barrier – PK link Lung Intestine Skin Absorption in minutes Absorption in hours Absorption in days 15  Properties of Medicines Medicine Quality How do we distinguish the quality difference ?? Regulation for medicines very strict Properties of Medicines Medicine Quality How do we distinguish the quality difference ?? 16  UK has good medicine quality – generics will still be tested. Properties of Medicines Medicine Quality – Each type of medicine has specific characteristics How do we understand tablet quality ? Manufacturing transferring method costs around £2 million. 17  Properties of Medicines Medicine Quality – Each type of medicine has specific characteristics How do we understand cream quality ? Properties of Medicines Medicine Quality – Drug quality (purity) – Excipient quality (purity) – Formulation quality Appearance Drug release Drug absorption Drug PK 18  Properties of Medicines Conclusion - The target product profile guides medicine design - A drug has certain intrinsic behaviours (physical chemical properties) - A formulation holds the drug to make a medicine and either conserves the drug’s behaviours or adapts them (e.g. delivery routes) - A medicine must store the drug and maintain high quality Properties of Medicines Quick Quiz…. 19