Floating topic
Laboratory work
Dissolution
Report
1 step method protocol
2+ drug product formulations
Drug API
- Enough drug for calibrators
Evaluate discrimination potential
Assess dissolution to 100% potential
Target "objective" media
Equilibrium solubility
Write report
In house solubility protocol
Analytical method
Standard conditions
- Temperature preferably 37C
- Agitation, orbital 200-300 RPM
Standard setup
- 3 Timepoints, 8, 24, 32 hours
- Triplicate each timepoint
- Unipreps, 0.5 ml media + 1-2 mg of drug
Understand the USP solubility 1236
Drug
How much drug do we need?
- 1 gram will be enough if we do the optimized protocol
Target specific media
- From the data produced in the drug screening, it should be possible to narrow the solubility study to a relatively small number of media
Solubility data (excel)
HPLC method development
Deliverables
Standard method for solubility and dissolution studies
Develop common HPLC method for relevant media
- If it's not possible to develop a common HPLC method, develop individual ones for specific media
Establish HPLC background
Develop a robust method to analyse the drug substance
Develop a standard scoping method
Drug screening
Kinetic solubility
Deliverables:
- Are the presented media capable of dissolving the drug to an in vivo similar concentration?
- Which media should I use to test equilibrium solubility?
- Which media should I use to test dissolution of the drug?
Method development
Method protocol
Standard media
Focused surfactant zone
Focused pH zone
BCS water solubility
Define essential requirements for HPLC method development
Understand approximate solubilities of the drug in relevant media
Evaluate the appropriate media to use in equilibrium solubility
Drug profiling
Deliverables:
- Define the best working conditions for the drug
Develop the screening method
Write up a drug profiling protocol
Establish the tests needed
Thermal
UV stability
Acid/base stability
Oxidation stability
- To test for oxidative, it is suggested to use hydrogen peroxide in the concentration range of 3 to 30 %
Study literature methods
Basic HPLC analysis
Evaluate if our laboratory has the capacity to work with the drug
Evaluate the optimal working conditions
Biopharmaceutical summary
This step consists on gathering the essential information needed to understand the drug being studied.
Deliverables of this step:
- A report on the drug substance and drug product properties.
- Predict the drug behaviour
Activities
Update databases and relevant literature
Databases and websites to use:
- Drug bank, https://go.drugbank.com/
- NCBI, https://www.ncbi.nlm.nih.gov/
- Swiss ADME, http://www.swissadme.ch/
- FDA drug database, https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases
- Sci-Hub
- https://bnf.nice.org.uk/
Set up drug knowledge database that can be used in the prescription
Research compound properties and fill excel biopharmaceutical summary
Resources
Subtopic
Objectives
Evaluate the drug's Biorelevant workability and predict biorelevant media to use
Set up drug knowledge database that can be used in the prescription (excel)
Write report on the drug substance and drug product properties.
