Biomedical Engineering Reference
In-Depth Information
4.5.3
Drug Delivery
Gel-like materials based on POE IV constitute AP Pharma's “Biochronomer”
delivery technology, and a Phase III clinical trial for the delivery of granisetron,
an established 5 - HT
3
receptor antagonist, to prevent chemotherapy-induced
nausea and vomiting (CINV) has just been completed. In addition, a Phase II
clinical trial to treat postoperative pain using the analgesic agent mepivacaine has
also been completed.
4.5.3.1
Development of APF 112 Mepivacaine Delivery System
Following surgery, currently used local anesthetics using a simple injection are
only effective for a few hours. An important advance would be the development
of a system that would result in the sustained delivery of a local anesthetic for a
few days thus reducing the need for opiate use with their well-know side-effects.
Further, if the delivery system is placed within the surgical incision, it should be
possible to maintain a high local concentration without a concomitant high sys-
temic concentration. This is important in view of the toxicity that mepivacaine,
the local anesthetic used, shares with other amide local anesthetics [32].
4.5.3.2
Formulation Used
The structure of the gel-like material used is shown in Scheme 4.13. In order to
improve injectability and ease of handling, the molecular weight of the polymer
was limited to about 6 kDa and methoxy polyethylene glycol having a molecular
weight of 550 Da was used as an excipient.
The actual composition of the clinical formulation designated as APF 112
was 77.6 wt% polymer, 19.4 wt% methoxy polyethylene glycol, and 3 wt%
mepivacaine.
O
O
O
+
+
HO-(CH
2
-C-O)
(C H
2
CH
2
O)
3
-H
HO-(CH
2
CH
2
O)
3
-H
x
O
O
O
O
O
O
O
O
O
O
C-O
O
O
O
O-R
O
CH
2
R'
n
x = 1- 7
R = R' = -(CH
2
CH
2
O)
3
-
Scheme 4.13
Structure of AP 530 used in clinical trials.
