L20 - Drug Solubility And Dissolution Rate 5 Flashcards
What are non-ionic surfactants? (3)
- hydroxyl and ether groups
- less polar than ionised groups
- need more units to produce an effective polar moeity
What is linked to POE chains with 20 or more ether groups?
Non-polar moiety
- several POE chains linked to cyclic sugar (sorbitan), linked to an alkyl group
What does the POE (number) equal?
(Number) of monomeric POE groups in the molecules
What are the surfactant applications? (4)
- anionic
- cationic
- nonionic
- parenteral
What are the anionic surfactant applications? (3)
- used bc cheap
- toxicity: only external use
- O/W emulsifiers
What are the cationic surfactant applications? (3)
- disinfectant, preservative applications
- O/W emulsifiers
- toxicity
What are the nonionic surfactant applications? (3)
- O/W and W/O emulsifiers
- low toxicity and irritancy
- oral and parernteral use
What are the parenteral surfactant applications? (1) + (4)
Ionic
- hemolysis of RBC and destruction of T lymphocyte cells
Nonionic
- phospholipids, lecithin <= 5%
- polysorbates 80 < 2%
- cremophor EL anaphalactyc shock
- toxicity of nonionic related to residual contamination of ethylene oxide
What are the hydrophobic portion of surface active drugs?
Aromatic or heterocyclic ring system
What are the examples of hydrophobic portions of surface active drugs? (4)
- tranquilizers, chlorpromazine
- antidepressants, imipramine
- antihistamines, diphenydramine
- antibiotic, penicillin G
What is solubilisation?
Process by which, water-insoluble or partly-soluble substances are brought into aq solution by incorporation into micelles
What are the part of micelle like in solubilisation? (3)
- Palisade layer - CHO + polar moieties + some water
- Core - CHO moieties of the S
- Surface or mantle - polar head groups + water
What does the site of solubilisation depend on?
The chemical nature of the solubilisate
The more polar the solute, the more likely to…
Be solublised close to the surface
The polar region of a non-ionic micelle is…
Significantly larger than that of an ionic micelle
What is the solubilisation capacity? What does it measure?
Solubilisation ratio and efficiency
- measures the ability of a surfactant to solubilise a solute
What is the molar solubilisation capacity (k)?
The number of moles of solute that can be solubilised by 1 mole of micellar surfactant
What is the eqn for k?
K = Stotal - Swater / Csurfactant - CMC
Sm = molar solubility of the solute in the micelle
Cmic = molar conc of micellar surfactants
What are non polar region directly related to?
Solubilisation capacity of low polarity solutes
How are nonpolar regions directly related to the solubilisation capacity of low polarity solutes? (3)
Increase HC chain
- larger nonpolar region - solubilise more solute
- decreased cmc
Introduction of a polar group, db in the chain
= decrease length of the chain
Branched surfactants
- smaller micelles
What are the 4 things selected for during surfactant selection?
- amount of surfactant that can be placed in water
- ability to solubilise a solute
- inc chain length = dec cmc and solubility
- balance required in practice
What are very long chains like as surfactants?
Not effective
- low solubility
What are very short chains like as surfactants? (2)
- solubilise a solute
- very high cmc
(Require high [surfactant])
What does a reduction of CMC corresponde to?
Decrease in surfactant solubility
- reduces the amount of surfactant that can be used
What does an increase in chain length in two carbons lead to?
Decrease solubility 10 fold
What are surfactants like in practice?
- 12-16 C or 18 with db
= provides low CMC, sufficient water solubility
What does the lipophilic part limit and what must the hydrophile provide?
- solubility in water
- enough interaction with water to bring the insolible lipophile into solution
What happens as chain length increases? (2)
- solubility decreases
- surface activity becomes more pronounced
The longer the HC chain, the…
Greater the tendency of the surfactant molecules to adsorb at the surface
= lower the surface tension
What is lundelius’s rule?
Any factor that tens to decrease solubility of the surfactant promotes surface activity
What does a high HLB number indecate?
A surfactant exhibiting mainly polar or hydrophilic properties
What does a low HLB numbers represent?
Lipophilic or nonpolar properties
What does a mixture of high and low HLB surfactants sometimes give greater of?
Stability than single surfactant
What is the HLB of a mixture of surfactants eqn?
HLBmixture = x HLBA + (1-x)HLBB
X - fraction of surfactant A, having HLBA
(1-x) - fractoin of surfactant B, habing HLBB
What does the addition of a surfactant reduce?
the interfacial tension between oil and water
How are surfactants used for emulsions?
To stabalise them
= emulgent
What does each type of oil require?
An emulgent of a particular HLB number in order to ensure a stable emulsion
- to form stable w/o or o/w
= required HLB
Why does the HLB of an emulsifier vary in temp?
The relative solubilities of the lipophile and hydrophile parts vary with temp
When is the effect of temp on the HLB of an emulsifier more pronounced?
When it’s for nonionic surfactants
- their solubility depends on H bonding
What are H bonds like at higher temps, what does this cause the emulsifier to be? (2)
- H bonds are weakened by thermal forces
- emulsifiers are less soluble in water
What are common nonionic emulsifiers? (2)
- water soluble at low T, stabilise o/w emulsions
- oil soluble at high T, stabilise w/o emulsions
What is the PIT of an emulsifier?
T at which it changes from being an o/w emulsifier to an w/o emulsifier
- hydrophilic and lipophilic nature just balance
