1. OPTIMISING MEDICINES DEVELOPMENT
DR KHULOUD T. AL-JAMAL
Institute of Pharmaceutical Science
King’s College London

2. Learning outcomes Discovery of new and better medicines
Describe the problems commonly associated with making medicines and their bioavailability
Explore conventional dosage forms and emerging medicines
Describe how pharmaceutical contribute to solving problems as “scientists”
Commonly used drug testing methods

3. The long road to a new medicine

4. Examples of “Drug Discovery” at King’s
Anticancer – in phase II clinical trial
(Leukaemia)
Iron Chelator – used in thalassemia
Experimental pre-clinical drug entering into Phase I clinical trial in Pancreatic and Breast Cancer
Phase II Clinical Trial in COPD

5. Tablet manufacturing process
Tablet Press
Blistering Machine

6. Solid oral dosage dissolution
Intact tablet
Disintegration
Deaggregation
Low rate of dissolution
Moderate rate of dissolution
Relatively rapid rate of dissolution
Diffusion and Absorption
Dissolution and diffusion
Drug in molecular form
Diffusion and Absorption

7. Routes of permeation Unstirred water layer Drug in solution
Tight junction
Intercellular space
Basement membrane
Blood capillary
Transcellular
Paracellular
Apical cell membrane

8. Problems… Poor aqueous solubility of the drug
Poor lipid solubility of the drug
Poor chemical and biological stability (e.g. against enzymes, pH)
Narrow therapeutic index
Poor penetration of the Blood Brain Barrier (BBB) for treatment of brain diseases

9. Solutions…
Addition of co-solvents, solubilisers, micronisations of drug…etc.
Chemical modification to facilitate absorption across biological membranes..etc.
Enteric coating of tables, encapsulation into nano-carriers…etc.
Controlled release formulations
Polymeric membrane
Drug molecules
Hydrophobic core

10. Examples of “Nano-carriers” at King’s
DENDRIMERS
Proceedings of the National Academy of Sciences USA, 2010, 107,
CARBON NANOTUBES
VIRAL CORE PARTICLES
Proceedings of the National Academy of Sciences USA, 2011, 108,
Nature Materials, 2009, 9, 485–490
The journal of biochemistry. 2013, 153,
Drug Radionuclide siRNA
LIPOSOMES
Small. 2008, 4,
Mol Pharm. 2009, 6,
Targeting ligand
Hydrophilic drug
Hydrophobic drug
POLYMERIC NANOCAPSULES HYBRIDS

11. In vitro and in vivo models
MONOLAYER
3D SYSTEM and CO-CULTURE
3D models (Spheroids)
- Targeting Targeting
Non-endosomal
Targeted NC
Non targeted NC
IN VIVO TESTING
Blood brain barrier model
Kupffer cells
(liver macrophages)
Cancer cells
Endosomal
SPECT/CT
FLUORESCENCE

12. OPTIMISING MEDICINES DEVELOPMENT
DR KHULOUD T. AL-JAMAL
Institute of Pharmaceutical Science
King’s College London