Sustained release formulations using non-aqueous carriers
Inventors
Houchin, Mary L. • Lee, Robin H. • Qi, Hong • Oehrtman, Greg • Jennings, Robert N. • Coleman, Scott H.
Assignees
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Publication Number
US-8895033-B2
Publication Date
2014-11-25
Expiration Date
Abstract
The disclosure provides one-component, injectable, sustained release formulations which comprise microspheres containing active pharmaceutical ingredients (e.g., exenatide), wherein the microspheres are suspended in a non-aqueous carrier. The non-aqueous carrier can be an oil, a fractionated oil, triglycerides, diglycerides, monoglycerides, propylene glycol fatty acid diesters, and the like. The formulations offer distinct advantages of long shelf life for the stability and potency of the formulation and sustained release of active pharmaceutical ingredients to reduce the frequency of medication dosing and to increase patient compliance.
Core Innovation
The invention relates to a manufactured pre-mixed formulation for injection that is a suspension of microspheres in a pharmaceutically acceptable non-aqueous carrier comprising one or more triglycerides. The microspheres comprise a biocompatible, biodegradable polymer and an active pharmaceutical ingredient, and the formulation is pre-mixed and manufactured for injection. The carrier is defined by a fatty-acid composition based on the total fatty acid content of the one or more triglycerides.
The fatty-acid composition of the triglyceride carrier includes from 0 to 2 wt % of C6 fatty acid, from 50 to 65 wt % of C8 fatty acid, from 30 to 45 wt % of C10 fatty acid, and from 0 to 2 wt % of C12 fatty acid. The disclosed carrier is non-aqueous and triglyceride-based, including MCT oils such as MIGLYOL 812.
In certain embodiments, the microspheres comprise a poly(lactide-co-glycolide) polymer with a lactide:glycolide ratio of about 1:1 and include about 2 wt % sucrose and about 5 wt % exenatide as the active pharmaceutical ingredient. The document further describes kit formats including pen injector, vial, and cartridge container formats, supporting prepared, one-component formulations intended to avoid mixing steps.
The problem addressed in the background is the need for long shelf life and improved stability of injectable sustained-release formulations while controlling release behavior, including reduced burst release and favorable pharmacokinetic profiles. The disclosed solution is a non-aqueous triglyceride carrier with defined fatty-acid composition and microspheres containing a biodegradable polymer and active pharmaceutical ingredient, optionally with sucrose stabilization, to support sustained release performance in pre-mixed injectable formats.
Claims Coverage
The provided independent claims are directed to a manufactured pre-mixed injectable suspension with a triglyceride-based non-aqueous carrier having specified C6/C8/C10/C12 fatty-acid ranges, and, for the second independent claim, microspheres defined by a poly(lactide-co-glycolide) polymer, about 1:1 lactide:glycolide, sucrose, and exenatide.
Manufactured pre-mixed injectable suspension in defined triglyceride carrier
A manufactured pre-mixed formulation for injection comprising a suspension of a pharmaceutically acceptable non-aqueous carrier comprising one or more triglycerides and microspheres comprising a biocompatible, biodegradable polymer and an active pharmaceutical ingredient, wherein the carrier comprises from 0 to 2 wt % of C6 fatty acid, from 50 to 65 wt % of C8 fatty acid, from 30 to 45 wt % of C10 fatty acid, and from 0 to 2 wt % of C12 fatty acid based on the total fatty acid content of the one or more triglycerides.
Defined PLGA microspheres with sucrose and exenatide
A manufactured pre-mixed formulation for injection comprising a suspension of a pharmaceutically acceptable non-aqueous carrier comprising one or more triglycerides with the specified C6/C8/C10/C12 fatty-acid ranges, and microspheres comprising a poly(lactide-co-glycolide) polymer, about 2 wt % of sucrose, and about 5 wt % of exenatide as the active pharmaceutical ingredient, wherein the ratio of lactide:glycolide in the polymer is about 1:1.
The inventive coverage centers on a pre-mixed injectable suspension in a defined non-aqueous triglyceride carrier with constrained C6/C8/C10/C12 fatty-acid contents, and, in one claim, microspheres that specifically use poly(lactide-co-glycolide) with about 1:1 lactide:glycolide and include sucrose and exenatide.
Stated Advantages
Long shelf life.
Reduced burst release.
Improved stability and potency in liquid storage.
Simplified patient handling by providing a pre-mixed one-component formulation.
Documented Applications
Injectable sustained-release formulations for injection using microspheres suspended in a non-aqueous triglyceride carrier, including kit formats such as pen injector, vial, and cartridge.
Pre-mixed injectable product intended for administration without a mixing step [procedural detail omitted for safety].
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