Biomedical Engineering Reference
In-Depth Information
stabilizer) and 0.329 g of ivermectin. The crosslinking agent,
n
- hexane - 1,2,6 - trio1
(0.289 g), was mixed with the composite and quickly extruded into l/32
ID FEP
tubing (Cole-Parmer) and cured at 70 °C for 16 h. The tubing was cut and removed
to yield highly fl exible elastomeric matrices which were cut to length. Drug-free
matrices were prepared in similar fashion.
″
4.2.2.3
Results
The behavior of the strands was investigated in dogs and the rate of ivermectin
release was estimated from an implant retrieval study since plasma levels were
below assay detection limits. The
in vivo
release rate was approximately 38
g/
month/cm of device. A correlation of the amount of drug remaining in the device
with the amount of residual polymer suggested that erosion was a major determi-
nant in the release of ivermectin, as would be expected for a system where iver-
mectin is chemically bound to the polymer.
On the basis of the data obtained, it was concluded that the crosslinked strands
are capable of providing canine heartworm profi laxis for more than 6 months [14].
Unfortunately, it was not possible to develop devices that would erode in a predict-
able and reproducible fashion so that this system was never commercialized.
μ
4.3
POE IV
POE IV was developed to overcome diffi culties in controlling the rate of erosion
of POE II and to make it more generally useful.
4.3.1
Polymer Synthesis
POE IV is prepared by the reaction between the diketene acetal DETOSU, a diol,
or mixture of diols and a latent acid diol, as shown in Scheme 4.8 [15]. An alternate
diketene acetal described under Section 4.2.1 and a diol can also be used.
4.3.1.1
Typical Polymer Synthesis Procedure
In a dry- box, 2.163 g (15 mmol) of
trans
- CDM, 4.727 g (40 mmol) of HD, 6.007 g
(40 mmol) of TEG, and 1.041 g (5 mmol) of the triethylene glycol glycolide
(TEG-GL) were dissolved in 40 g of THF. Then, 21.437 g (101 mmol) of
3,9- diethylidene - 2,4,8,10 - tetraoxaspiro [5.5] undecane were weighed into a round -
bottom fl ask and added to the diols solution with the aid of 20 g THF, in several
portions. The fl ask was removed from the dry-box, rapidly connected to a con-
denser and nitrogen inlet, and a few drops of
p
- toluenesulfonic acid solution
(10 mg/mL) added. After the exotherm subsided, the solution was slowly poured
into 3 L of methanol, containing about 1000 ppm of triethylamine. After isolation
by fi ltration and drying in a vacuum oven at 40 °C for 24 h, the yield was
32.1 g (89.7%).
