Prescription - Laboratory work

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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

• 3*3 = 9 vials per media

• pH measurement

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

• 22C vs 37C

UV stability

• ICH Topic Q1B, "suntest"

Acid/base stability

• From pH 1.2 to pH 7.4

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.