Formulation

Question 1

pH conversion & predominant form

Answer 1

pH = pKa —> HA = A- or B = BH+
I unit = 90.0%
2 units = 99.0%
3 units = 99.9%
(above = A- / B; below = HA / BH+)

Question 2

Log D (at pH 7) in terms of solubility & absorption

Answer 2

Log D < 1 = too polar good solubility, poor absorption
Log D 1-3 = best balance between solubility & absorption
Log D > 3 = very non-polar, poor solubility

Question 3

Intranasal characteristics
(Total volume, total surface area, dose, olfactory region)

Answer 3

Total volume = 15-20 mL
Total SA = 150 cm3
Dose = 100-150 micrometer
Olfactory region = 15 cm2

Question 4

Lipinski’s rule of 5 (for nasal delivery)

Answer 4

1. < 5 H bond donors
2. < 10 H bond acceptors
3. Molecular weight < 500 Da
4. Log P < 5 & unionised
5. Particle size > 10 micrometer

Question 5

Nasal spray formulation considerations (5)

Answer 5

1. Priming ( >7d = re-prime)
2. Viscosity (higher = longer residence = bad)
3. Particle size (smaller = travel further = good)
4. Osmolarity (hypotonic 300-700 = better permeability)
5. Spray pattern & plume geometry

Question 6

Excipients for intranasal
(Solubility, permeation enhancer)

Answer 6

Solubility: Glycerol, PEG
Permeation enhancer: Fatty acid, cyclodextrin

Question 7

Mass Median Aerodynamic diameter (MMAD)

Answer 7

MMAD > 10 = intranasal
5 > MMAD > 1 = therapeutic interest for aerosol (pulmonary)

Question 8

Factors for aerosol deposition (6)

Answer 8

1. Inertial impaction: Stokes < 1 = good
2. Gravitation sedimentation & force: small particle + low density = good
3. Velocity: lower = deeper in lung = good
4. Buoyancy force: lower = suspended = good
5. Drag force = lower = better
6. Brownian diffusion = bigger = better

Question 9

CNS Lipinski’s rule of 5

Answer 9

< 450 Da
H bond donor < 3
H bond acceptor < 7
Log P 1-3
Unionised

Question 10

Suppository base amount equation

Answer 10

Amount of base = (number of suppository x Calibration value) - (number of suppository x drug amount / displacement value)

Question 11

Displacement value equation

Answer 11

DV = Weight of drug / weight of base displaced by drug

Question 12

Excipients list:
1. Diluent
2. Surfactant
3. Buffer
4. Preservatives
5. Co-solvents
6. Permeation enhancers
7. Suspending agents
8. Tonicity adjusters
9. Viscosity enhancers

Answer 12

1. Diluent = lactose
2. Surfactant = Polysorbate 80
3. Buffer = sodium phosphate
4. Preservatives = benzalkonium chloride
5. Co-solvents = PEG
6. Permeation enhancers = Oleic acid
7. Suspending agents = MCC
8. Tonicity adjusters = sodium Chloride
9. Viscosity enhancers = CMC

Question 13

Properties of Ideal Parenteral Formulations

Answer 13

1. pH (IM: 3 - 11, SC: 3-6)
2. Tonicity (280-290 mOsmol/L) for large vol parenterals - hypertonic is preferred
3. No visible particles (more for IV than SC/IM)

Question 14

Hydrophile-Lipophile-Balance (HLB) for Emulsifiers

Answer 14

Scale from 0 (Hydrophobic - oil soluble) to 18 (Hydrophilic - water soluble)
HLB > 10 –> o/w emulsion more likely to be formed