US 2004/0105878 A1 · Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers

Abstract

Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.

Claims26

Dependent claims

A method of stabilizing a biologically active agent in a biodegradable polymeric delivery system, comprising:

a) forming a polymer solution comprising a solvent and a PLGA polymer which comprises from 50 to 100% lactide or lactic acid and from 50% to 0% glycolide or glycolic acid, wherein said lactide or lactic acid is selected from the group consisting of the L isomer, the D isomer, or a D,L racemic mixture;
b) blending from 10% to 40% (w/w) of a pore forming agent with the PLGA polymer solution to provide a resulting solution comprising the polymer and pore forming agent;
c) dispersing the biologically active agent in the resulting polymer solution;
and
d) solidifying the polymer from the resulting polymer solution to provide a biodegradable polymeric system whose microclimate homogeneously maintains a pH of greater than 4 and less than 8 throughout substantially all pores within the polymer during biodegradation for at least 4 weeks.

2 more elements

Dependencies are inferred from the claim text.

Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers

Life of this patent

Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers

Life of this patent

Abstract

Claims26