Page 106 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

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

• Hence dissolution occurs under sink conditions, that is, under conditions such

that the value of (Cs - C) approximates to Cs. Thus, for the dissolution of a

drug from the GIT under sink conditions the Noyes-Whitney equation can be

:
expressed as
dC / dt = D A Cs / h

(C). Drug factors affecting dissolution rate

(a) Surface area and particle size

(b) Crystal form
(c) Solubility in the diffusion layer, C

(d) Salt formation
(a). Surface area and particle size

 According to the Noyes-Whitney equation, an increase in the total surface area

of drug in contact with the GI fluids will cause an increase in dissolution rate.

 The smaller the particle size, the greater the effective surface area exhibited by a

given mass of drug, the higher the dissolution rate.

 Particle size reduction is thus likely to result in increased bioavailability, provided

the absorption of the drug is dissolution-rate limited

 Griseofulvin
A reduction of particle size from about 10 µm to 2.7 µm was shown to produce

approximately double the amount of drug absorbed in humans.

 Many poorly soluble, slowly dissolving drugs are routinely presented in

micronized form to increase their surface area.

The particle size reduction is not always desirable (why?)

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