lecture 2

Question 1

Importance of bulk density?

Answer 1

• size of the final dosage form.
  -considers the size of a
  high-dose capsule product or the homogeneity of a low-dose formulation in
  which there are large differences in drug and excipient densities.
• affects their flow properties.

Question 2

Importance of Solubility?

Answer 2

Drugs need to be soluble, increased dissolution rate, entering systemic circulation, and therefore improved therapeutic effect

Question 3

Initial Solubility Determination?

Answer 3

Equilibrium Solubility Method

Question 4

Equilibrium Solubility Method?

Answer 4

1-An excess of the drug is placed in a solvent and shaken (in a shaker)
at a constant temperature over a prolonged period of time until equilibrium.
2- Chemical analysis of the drug content in solution is performed to determine the
degree of solubility.
• Conduct initial solubility on only a few solvents: water, 0.9%NaCl, 0.1 M HCl, 0.1 M NaOH

Question 5

factors affecting solubility?

Answer 5

• temperature
• common ion effect
• partition coefficient
• dissociation constant
• solubilization
• dissolution rate

Question 6

the principle involved in common ion effect?

Answer 6

Le Chatelier’s principle

Question 7

Applications of common ion effect on solubility

Answer 7

1- In gastric juice, where the pH can range from 1-2 and the chloride ion
concentration, doxycycline hydrochloride dihydrate (factor of 7 less than its solubility in distilled water).
2- In adjusting the isotonicity of I.V. and ophthalmic products by NaCl, there may be a
common ion effect with some drugs e.g. pilocarpine HCl.
3- It is possible to retard the degradation of Procaine penicillin by making the drug less
soluble (common ion effect) if prepared with procaine HCl. (The stability was
significantly increased).

Question 8

Applications of Partition coefficient on solubility

Answer 8

Hydrophobic drugs= crosses the cell membrane
Hydrophilic drugs= stays in the blood compartment
Drug extraction
predicated drug absorption
Ointment: High P.C. favors the oily base. This retards the release of the drug from the base thus decreasing the therapeutic effect.
Topical/Transdermal dosage forms: partition coefficient is important in establishing the flux of a drug through the stratum corneum

Question 9

the principle involved in PKA

Answer 9

Henderson-Hasselbalch equation

Question 10

Provide an example of a drug whose PKA is equal to its ph

Answer 10

phenobarbital has a pKa= 7.4, and in plasma (pH 7.4) it is present as ionized and unionized forms in equal amount

Question 11

the principle involved in the dissolution

Answer 11

Noyes-Whitney equation

Question 12

How to increase solubility *IMP

Answer 12

-mixed solvents: Co-solvents such as ethanol, propylene glycol
-surfactant and cosurfactant
-Complex formation
-Micronization
- Solid dispersion
-chemical modification of the drug into salt or ester forms is a technique frequently
used to obtain more soluble compounds or introduction of polar groups as OH

Question 13

4 forms of stability

Answer 13

Solid-state stability
Bulk stability
compatibility stability
solution stability

Question 14

Degradation is monitored by either determination of the remaining amount of compound with
respect to time or through the appearance of degradation product mostly_____

Answer 14

hplc

Question 15

how to test Stability in solution?

Answer 15

Hydrolysis
Oxidation
Racemization
Photochemical degradation