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Dosage forms
If not a solution the drug must be liberated from its dosage form
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Drugs must have sufficient____ solubility and _____ solubility
- Water- be in molecular form in body
- Lipid- traverse lipid membranes
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Drug properties for preformulation
- Physical properties
- Dissolution
- PArtitioning
- Stability
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Crystalline form
Common. Has a repeating arrangement of the individual molecules that creates the crystal lattice.
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Crystal habit defined by
The internal structure
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Different habits can result from
minor changes in synthetic conditions
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Amorphous form
No repeating arrangement, molecules are random no crystal lattice... looser arrangement
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Flow properties
Important for dosage uniformity
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Bioavailabity
Function of drug dissolution, fraction of administered drug that reaches systemic circulation.
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Solid state stability
hygroscopicity and polymorphism
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Metastable
Being in an unstable or transient but relatively long lived state of chem or physical form.
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Metastable polymorphs are generally ___ soluble that their _____ stable counterpart. This is due to what?
- more soluble
- More stable
- Weaker interaction
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psuedopolymorphisms
Hydrates or solvates
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solvate solubilty
changes in hydrate form can affect solubility.
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T/F Hydrates are more soluble than their anyhydrous counterparts.
False
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Detection of polymorphism is by?
Melting points, different polymorphs= different melting points.
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Griseofulvin
micronization reduced dose by 50%
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Nitrofurantoin
Crystals were too small, dissolved too fast caused nausea
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Particle flow effects
- Mixing and pouring
- Speed of processing during manufacture
- Settling or statifying
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Factors for particle flow
Electrostatic, absorbed moisture, density, shape, size.
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miscible liquids
liquids dissolved in each other
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Halothane
General anesthetic (gas+liquid)
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Dissolution of crystalline solute
- 1) remove solute from molecule
- 2) create hole in solvent
- 3) place solute in hole
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Solubilty definition
Amount dissolved per volume
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Hydrophilic substituents hydrogen bond with ______
Water
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Phenol is 100X more soluble than _____ due to what?
Benzene due to hydrophilic substituents.
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Estraidiol
corticosteroid ring structure with 2 hydroxyl groups, solubility is 5 mcgrams/mL
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Ionization state is one of the most important physicochemical properties.
Affects dosage formulation, absorption, distribution, and excretion.
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pH=pKa + log (A-/HA)
- Hendersen hasselbeck
- A- salt
- HA Acid
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Weak Acid solubility equation
pH=pKa + Log ([S-So]/So)
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Weak base equation
Same but flip the So/[S-So]
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What does S and So stand for
- S is overall solubilty
- So solubility in unionized form
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Solvent pH affects the drugs
Ionization state
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Surfactants and Cyclodextrins are examples of
Solubilizing agents
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T/F dissolution is an exothermic process because energy is needed to break bonds in the solid.
False! Endothermic.
Greater heat input generally leads to greater solubility of a solid.
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Creation of solid form must consider several properties
Solubility and stability (hydroscopicity and metastability)
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Griseofulvin/PEG known for
Significant solubility improvement
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Very common method of altering a drug's properties.
Salt formation
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How salt is formed:
Salt is crystallized from the solvent
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T/F Salt formation is only for increasing drug solubilty.
False, can increase or decrease
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T/F A drug in suspension is more stable than a drug in solution.
True
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Decreased drug solubilty can help mask
Taste
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T/F Propoxyphene napsylate is less bitter than Propoxyphene hydrochloride because it is more soluble.
False! Because it is LESSSSSS Soluble
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Salt can improve solubilty thus
Greater degree of interaction with Water molecules.
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