Semaglutide depot systems and use thereof
Inventors
ZATS, Galina • BLEICH KIMELMAN, Nadav • Rubnov, Shai • Marom, Ehud
Assignees
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Publication Number
US-11865213-B2
Publication Date
2024-01-09
Expiration Date
Abstract
The present invention provides parenteral pharmaceutical compositions comprising therapeutically effective amounts of semaglutide or pharmaceutically acceptable salts thereof, the parenteral pharmaceutical compositions are formulated in depot form and provide low-burst release and a continued release profile. The present invention further provides methods of use of the parenteral pharmaceutical compositions for treating type-2 diabetes mellitus, obesity, and Parkinson's disease.
Core Innovation
The invention relates to a long-acting parenteral pharmaceutical composition comprising dried microparticles that include semaglutide or a pharmaceutically acceptable salt thereof and a biodegradable carrier at a specified carrier-to-drug ratio. The dried microparticles are formed from water-in-oil-in-water (w/o/w) double emulsion droplets and are devoid of any coating layer. The composition is defined by semaglutide release in phosphate buffer at pH 7.4, including low burst and sustained release profiles over extended periods.
A key aspect is that the composition releases less than 20% of semaglutide over 24 hours, releases less than 80% over 14 days, and releases more than 80% over 28 days in phosphate buffer at pH 7.4. The semaglutide active ingredient is released in a continuous manner over 14 days upon dissolution in phosphate buffer at pH 7.4. The overall release period is about four weeks to about two months.
The invention specifies that the dried microparticles are produced by drying w/o/w double emulsion droplets comprising an internal aqueous phase with semaglutide (or a pharmaceutically acceptable salt), a water immiscible polymeric phase with the biodegradable carrier selected from polylactides, polyglycolides, polycaprolactones, and combinations thereof, and a first surfactant comprising a fatty acid or a derivative thereof, and an external aqueous phase containing a tonicity modifier comprising sodium chloride. The resulting composition is characterized as a long-acting depot composition suitable for administration in a medically acceptable location with a dosing frequency of once every four weeks to once every six months.
Claims Coverage
The independent claim defines a long-acting depot parenteral composition with coating-free semaglutide-loaded microparticles derived from w/o/w double emulsion droplets, a defined biodegradable carrier ratio, specified surfactant and tonicity components, and quantitative phosphate-buffer release constraints.
Dried, coating-free semaglutide-loaded w/o/w microparticles with biodegradable carrier ratio
A long-acting parenteral pharmaceutical composition comprising dried microparticles comprising a therapeutically effective amount of semaglutide or a pharmaceutically acceptable salt thereof and a biodegradable carrier at a ratio of about 1:10 to about 1:15 (w/w), wherein the dried microparticles are formed by drying water-in-oil-in-water (w/o/w) double emulsion droplets and are devoid of any coating layer.
Specified phosphate buffer release thresholds at pH 7.4
The composition releases less than 20% of semaglutide over 24 hours in a phosphate buffer at pH 7.4, releases less than 80% over 14 days in a phosphate buffer at pH 7.4, and releases more than 80% over 28 days in a phosphate buffer at pH 7.4.
Continuous release over 14 days with overall four-weeks-to-two-month period
Semaglutide is released from the composition in a continuous manner over 14 days upon dissolution in a phosphate buffer at pH 7.4, and the composition releases the semaglutide active ingredient over a period of about four weeks to about two months.
Depot suitability for administration frequency range
The long-acting parenteral pharmaceutical composition is a long-acting depot composition suitable for administration at a medically acceptable location in a subject in need thereof at a frequency of once every four weeks to once every six months.
Double emulsion droplet components and excipient selection
The dried microparticles are formed by drying w/o/w double emulsion droplets comprising an internal aqueous phase with semaglutide or a pharmaceutically acceptable salt thereof, a water immiscible polymeric phase comprising a biodegradable carrier selected from polylactides, polyglycolides, polycaprolactones, and combinations thereof and a first surfactant comprising a fatty acid or a derivative thereof, and an external aqueous phase comprising a tonicity modifier comprising sodium chloride.
The inventive concept is anchored on dried, coating-free semaglutide-loaded microparticles made from w/o/w double emulsion droplets with a defined biodegradable carrier ratio and specified surfactant and tonicity components, combined with quantitative semaglutide release thresholds in phosphate buffer at pH 7.4 and an overall release period supporting depot administration once every four weeks to once every six months.
Stated Advantages
Minimal burst, characterized by release of less than 20% of semaglutide over 24 hours in phosphate buffer at pH 7.4.
Sustained release, characterized by release of less than 80% over 14 days and more than 80% over 28 days in phosphate buffer at pH 7.4.
Continuous manner release over 14 days upon dissolution in phosphate buffer at pH 7.4.
Reduced injection frequency enabled by a depot suitable for administration once every four weeks to once every six months.
Improved compliance and reduced local/systemic side effects are stated in the provided summary content.
Documented Applications
Treating type-2 diabetes mellitus using the disclosed long-acting parenteral pharmaceutical composition administered at a frequency of once every four weeks to once every six months.
Treating obesity using the disclosed long-acting parenteral pharmaceutical composition (as stated in the provided summary content).
Treating Parkinson’s disease using the disclosed long-acting parenteral pharmaceutical composition (as stated in the provided summary content).
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