Preformulation studies Flashcards
What are preformulation studies?
- ## studies that are used to identify the most ideal form of a pharmaceutical product from a manufacturing and formulation perspective.
- early drug development phase: preformulation studies were used to identify the physical, chemical, pharmaceutical and analytical properties of the candidate molecule, as well as how to modify them for better performance.
- established product:
determine the quality of raw materials in the samples of raw materials, API and the formulation.
What are the significance of preformulation studies?
- Predict viability of various formulations and methods of manufacture
- Identify best manufacturing process for optimal product performance.
- Confirm stability and bioavailability, reduce probability of product failure.
What is the purpose for conducting preformulation tests?
- Primary characterization of drugs based on their physical and chemical properties.
- Ensure product quality
- Provide important data that may influence a manufacturing process.
What are the benefits from conducting preformulation studies?
- Set specifications on API to ensure consistent, successive performances
- Minimise development costs
- Avoid failures during long-term stability
- Minimise the need for in vitro bioavailability studies
What is BCS classification used for, and what are the solubility and permeability levels in each of the classes?
- used to determine gastrointestinal permeability and the dissolution of the API in various pH mediums.
- BCS I: high solubility, high permeability
- BCS II: low solubility, high permeability
- BCS III: high solubility, low permeability
- BCS IV: low solubility, low permeability
What are the physical measurements available for measurement?
- Particle shape
2. Surface area
What are the techniques and measurements used to determine particle shape?
technique: image analysis
measurements:
- sphericity
- aspect ratio
What are the techniques and measurements used to determine surface area?
- BET - specific surface area
2. Estimate by eye
What is BET?
Can be measured using the gas adsorption technique, where small amounts of nitrogen gas are added to the solid molecule at cryogenic temperatures.
Due to the weak attractive forces from the solid molecules, the gas particles adsorb easily onto them.
Pressure and volume have a direct relationship according to gas law, therefore the measurement of pressure can determine the volume of the gas adsorbed.
What are the different types of densities and their measurement?
- true density = mass/volume (volume without voids)
2. apparent density: bulk density, tapped density, envelope density ( bulk density without inter-agglomerate voids)
What is the technique used to determine true density?
- gas pyncometry
- helium is used because it is small and inert.
- based on ideal gas law, volume can be determined directly from pressure.
What is the technique used to determine envelope density?
- unique displacement
- particles are placed in a free-flow filler bed, and stirred and agitated until they are completely enveloped.
- calculate density = weight of the particles added / total volume of the container
Why is determining the level of moisture in a material important?
- it affects the stability of the excipient
- also affects many unit operations in pharmaceutical manufacturing
What is the technique used to measure the level of moisture in a material?
- dynamic vapor sorption
- vapor concentration around the sample is modified, change in humidity results in change in mass balance in the microbalance nodule.
- extent of weight loss determines amount of moisture absorbed by the particle.
- & moisture content is plotted against water activity in a moisture sorption isotherm.
What are the advantages of dynamic vapor sorption?
- minimal sample size is required
- rapid analysis due to faster equilibrium
- higher accuracy and precision
