T1 - Week 4 Flashcards
Which is the most convenient route of drug delivery?
Oral
What is the disadvantage of oral dosage forms?
Poor bioavailability due to poor solubility and permeability
Define solubility
The amount of a solid solute that can dissolve in a given solvent at equilibrium
Define equilibrium solubility
The concentration of the solute in its saturated solution, where the saturated solution exists in a state of equilibrium with pure solid solute
Define kinetic solubility
The amount of the solute in solution prior to reaching equilibrium solubility
What are the steps of the solubility process?
- Solute-solute intermolecular bonds breakup
- Solvent-solvent intermolecular bonds breakup
- Formation of cavity for solute
- Transfer of solute into cavity
- Solute solvent intermolecular bond formation
What happens if solvent-solvent forces are greater than solvent-solute?
Solvent molecules will not want to dissociate the solute will be excluded
What happens if solute-solute forces are greater than solvent-solute?
The solvent will not be able to break and bind to solute
What happens if solvent-solute forces are greater than solvent-solvent or solute-solute?
Solute will form a solution
What are the USP classifications of solubility?
- Very soluble: less than 1mL/g
- Freely soluble: 1-10
- Soluble: 10-30
- Sparingly: 30-100
- Slightly sparingly: 100-1,000
- Very slightly soluble: 1,000-10,000
- Practically insoluble/insoluble: more than 10,000
Define miscibility
A homogenous solution of a liquid state in another liquid solvent at any concentration
What is dielectric property?
The ability of a molecule to store/carry a charge
What type of dielectric constant solvent can dissolve a highly polar or ionic compound?
High or a polar solvent
What type of dielectric constant solvent can dissolve a nonpolar compound?
Low
What is hydrogen bonding?
H bonds with electronegative elements that create partial polarity
What atoms would interact with hydrogen for bonding?
O, N, and S
Which is more soluble amorphous or crystalline nature of drugs?
Amorphous
Which is more soluble hydrous or anhydrous in water?
Anhydrous
Would high solubility have a high or low melting point?
Low due to molecular instability
Why would branched molecules have increased solubility?
Branching will reduce size of the molecule making it easier to solvate the molecules
What particle size would be the most soluble?
Small, to increase surface area to volume ratio
What occurs when solute is being dissolved?
Intramolecular forces of solute are being overcome
What happens to solubility when temperature increases?
Increases
What happens if the solubilization process is endothermic?
Increasing temperature improves solubility
What happens if the solubilization process is exothermic?
Increasing the temperature will decrease in solubility
How can you improve solubility of ionizable solutes?
Adjusting of the solution’s pH
How can you improve solubility of non-ionizable solutes?
Lowering the dielectric constant of the solvent with a co-solvent
Describe the solubility of weak acids?
Solubility increases if pH is above pKa
Describe the solubility of weak bases?
Solubility decreases as pH is above pKa
What are the general rules of water solubility?
- Water solubility of a solute can be enhanced by forming H-bonding
- Water solubility decreases with an increase number of carbons in a solute
- High melting point solids largely have low water solubility
What is comminution?
Using mechanical stress to disaggregate solid particles, however, may cause degradation of drug product
What is micronization and nanonization?
Reducing particle size to micron and nano level, increasing surface area of lipophilic drug to improve solubility
How do you enhance solubility of the drug by altering solid state?
Crystalline to amorphous
Selecting the highest soluble polymorphic form
What is a pharmaceutical solid dispersion?
A mixture of a solid drug with diluents (carriers)
A hydrophilic carrier and a hydrophobic drug
What is the inclusion complexes method?
Formed by the insertion of a nonpolar molecule (guest) into the cavity of another molecule or group (host)
What is a common host molecule?
Cyclodextrin: Hydrophobic cavity and hydrophilic outer surface
What are cosolvents?
Water-miscible organic solvent (lipophilic) that enhance aqueous solubility of poorly water soluble drugs
What are examples of cosolvents?
- Ethanol
- Glycerol
- Propylene glycol (400)
What are liposomes?
Vesicles obtained either from natural phospholipids or synthetically that carry poorly water soluble drugs while the hydrophilic compartments can load hydrophilic drugs
What is a prodrug?
Covalently bound drug where the inactive moiety will be cleaved upon administration to regenerate the parent drug in the body enhancing solubility of parent drug
What forms a salt?
Poorly water soluble weak acid or base + counterion
What is dissolution?
The process which a solid substance enters the solvent phase to yield a solution
What is the process of dissolution?
- Removal of the solute from the solid phase
- Accommodation of the solute in the liquid phase
- Diffusion of the solute away from the solid/liquid interface into the bulk phase
What factors are proportional to drug dissolution rate?
- Drug solubility
- Surface area of drug particles
- The concentration gradient of drug between the diffusion layer and bulk solution
What factors are inversely proportional to drug dissolution rate?
- The thickness of the diffusion layer surrounding the drug
- The volume of solution
