Compositions of a polyorthoester and an aprotic solvent
Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an aprotic solvent, and a drug are described. The solvent is selected to modulate release of drug from the composition, where, in some embodiments, the solvent is rapidly released after administration and provides a corresponding rapid rate of drug release. Alternatively, in other embodiments, the solvent is slowly released from the composition after its administration, and provides a correspondingly slow rate of drug release.
1. A delivery system, comprising:
a polyorthoester;
dimethyl sulfoxide in which the polyorthoester is miscible to form a single phase; and
bupivacaine dispersed or solubilized in the single phase;
wherein the polyorthoester is a polyorthoester of Formula III;
where
A is R 1 or R 3 ,
R* is C1-4 alkyl,
n ranges from 5 to 1000,
R 1 is:
p and q are integers that vary from between about 1 to 20 and the average number of p or the average of the sum of p and q is between 1 and 7;
R 3 and R 6 are each independently:
x is an integer of 0-10;
R 5 is H or methyl, and
the fraction of A units that are of formula R 1 is between 0 and 25 mole percent.
2. The delivery system of claim 1 , wherein bupivacaine is dispersed in the single phase.
3. The delivery system of claim 1 , wherein bupivacaine is solubilized in the single phase.
4. The delivery system of claim 1 , wherein the delivery system has a viscosity of less than about 10,000 cP at 37° C.
5. The delivery system of claim 1 , where the polyorthoester has a molecular weight between about 1,000 and 10,000 daltons.
6. The delivery system of claim 1 , wherein bupivacaine is in an amount of about 1-20 percent by weight of the delivery system.
7. The delivery system of claim 6 , wherein bupivacaine is in an amount of about 2-5 percent by weight of the delivery system.
8. The delivery system of claim 1 , wherein dimethyl sulfoxide is in an amount of about 10-60 percent by weight of the delivery system.
9. The delivery system of claim 8 , wherein dimethyl sulfoxide is in an amount of about 10-20 percent by weight of the delivery system.
10. The delivery system of claim 1 , wherein the polyorthoester is in an amount of about 50-80 percent by weight of the delivery system.