Cosolvents, Cyclodextrins, Buffers Flashcards
1
Q
Cosolvents
A
- Used to increase solubility of drugs (per amount of cosolvent added)
- EX: ethanol glycerin, propylene glycol, sorbitol, polyethylene glycol
2
Q
Addition of cosolvents causes…
A
- Change in dielectric constant of solution
- Make solution less polar
- Increase intrinsic solubility [HA] and [B]
3
Q
Cyclodextrins
A
- Enhance aqueous solubility
- Formation of inclusion complexes to use with hydrophobic compounds
- Hydrophobic cavity with a hydrophilic exterior
4
Q
Buffers
A
- Resist pH change upon addition of small quantities of acids/bases
- Weak acid and conjugate base OR weak base and conjugate acid
5
Q
Buffer Examples
A
- Acetic acid/sodium acetate
- Phosphoric acid/sodium phosphate
- Carbonic acid/sodium bicarbonate
- Citric acid/sodium citrate
6
Q
Common Ion Effect
A
- When a compound when a same ion when dissociated is added to a solution
- Increases in [Ac-] for example, would cause Ka to remain the same but [H3O+] to decrease
- Ionization of HAc is inhibited from the addition of the common ion
7
Q
Calculating Buffer Solution pH (Acid + Salt)
A
- [HAc] is the total concentration of acid
- [Ac-] comes almost entirely from salt
- [H3O+] = Ka * [Acid]/[Salt]
- Rewritten to: pH = pKa + log([Salt]/[Acid])
8
Q
Buffer Solution pH (Base + Salt)
A
pH = pKa + log([Base]/[Salt])
9
Q
Weak Acid and pH
A
[Salt]/[Acid] = 10^(pH-pKa)
- *If pH = pKa then there is 50% in the salt form and 50% in the acid form
- If pH>pKa (pH-pKa = positive number), then more drug is in salt form and is IONIZED
- Opposite is true with opposite conditions
10
Q
Weak Base and pH
A
[Base]/[Salt] = 10^(pH-pKa)
- *If pH = pKa then there is 50% in the salt form and 50% in the acid form
- If pH
11
Q
Calculating Buffer Capacity Steps
A
- Calculate pH
- Calculate new pH with base added
- Calculate Buffer capacity
12
Q
Buffer Selection
A
Select weak acid with a pKa approximately equal to the desired pH
Things to Consider
- High solubility in aqueous systems
- Exclusion by biological membranes
- Toxicity
- Chemical stability
- Well defined or non-existent interactions with mineral cations
- Cost of raw materials
- Readily available in pure form
13
Q
Selecting Bufering pH
A
- Drug solubility, drug stability, delivery site
- Ideally, buffer at pH = 7.4 (If pH>9, tissue necrosis; pH<3, extreme pain and phlebitis)
- Small volume parenterals (acceptable pH range 3-10.5), blood functions as carrer
- Need to find the compromise between max stability, solubility, tolerability, and biological activity
