Page 108 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

Example 1:
The antibiotic chloramphenicol palmitate
o This drug exists in three crystalline forms designated A, B and C.
✓ At normal conditions, A is the stable polymorph,
✓ B is the metastable polymorph and
✓ C is the unstable polymorph.
o Polymorph C is too unstable to be included in dosage form.
o The extent of absorption increases as the proportion of the polymorphic
form B is increased in suspension.
o The polymorph A dissolves slowly and hydrolyzed slowly to
chloramphenicol in vivo that this polymorph is ineffective.
Example 2:
Methylprednisolone
o It exists as a metastable & stable form.
o A suspension for SC injection containing the 2 crystalline forms
provides a sustained release of the drug.
o The metastable form provides a rapid initial dose (loading dose),
o while the stable form provides the prolonged or sustained action dose
(the maintenance dose).

o Another variation in the crystalline form can occur if the drug is able to associate

with solvent molecules to produce crystalline forms known as solvates

(pseudopolymorphism).

o When water is the solvent, the solvate formed is called a hydrate. The solvate is

called the anhydrous form.

o Generally, the greater the solvation of the crystal, the lower are the solubility and

dissolution rate in a solvent identical to the solvation molecules

Therefore, the anhydrous form generally dissolves more rapidly than the hydrous

form.

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