Pharmaceutical Manufacturing Handbook: Production and

924 PHARMACEUTICAL PREFORMULATION
C t = concentration of drug in bulk fl uid at given time
K = partition coeffi cient
h = thickness of stagnant layer
If the bulk volume is large and the concentration of drug in the fl uid is much
lower than the drug solubility ( C s > > C t ), it is regarded as a sink condition. In this
case, the equation is much simpler and the dissolution behaviors continuously occur
because the chemical potential ( C s − C t ) approximates drug solubility ( C s ).
In a matrix tablet, the following Higuchi equations are given depending on the
polymeric structures of the homogenous and porous matrix [20] :
1/2
⎧[
D( 2A−CS)
CSt]
for homogenous matrix
Q = ⎨
1/2
⎩[
Dε( 2A−εC
) C t ] / τ for
porous matrix
S S
In the dissolution of granular powders, the Hixson – Crowell equation is also
established as
1/3 1/3
Q − Q = kt for granular powders
0
Testing Method In addition to formulation and manufacturing controls, the method
of dissolution testing also must be controlled to minimize important variables such
as paddle rotational speed, vibration, and disturbances by sampling probes. The
USP includes seven apparatus designs for drug release and dissolution testing of
immediate - release oral dosage forms, extended - release products, enteric - coated
products, and transdermal drug delivery devices:
Apparatus I: rotating basket method, 25 – 150 rpm (100 rpm)
Apparatus II: rotating paddle method, 25 – 150 rpm (50 rpm)
Apparatus III: reciprocating cylinder method, inner tube (5 – 40 dips/min), outer
tube (300 mL)
Apparatus IV: fl ow - through method: 4 – 16 mL/min
Apparatus V: paddle over disc
Apparatus VI: cylinder method
Apparatus VII: reciprocating holder method
Detailed guidelines for dissolution testing are described in monographs of many
pharmacopeias. The USP apparatus I and USP apparatus II are used principally for
tablet dissolution testing. In USP apparatus I, the dosage unit is placed inside the
basket. In USP apparatus II, the dosage unit is placed on the bottom in the vessel.
In each test, a volume of the dissolution medium (500 – 900 mL in general) is placed
in the vessel and allowed to come to 37 ± 0.5 ° C. Then the stirrer is rotated at the
specifi ed speed (50 – 200 rpm). The samples of the medium are withdrawn for analysis
of the proportion of drug dissolved. The tablet or capsule must meet the stated
monograph requirement for rate of dissolution. For example, “ not less than 85% of
the labeled amount is dissolved in 30 minutes in case of immediate release tablet. ”
In a fl oating tablet, the sinker can be used in the paddle method.