Method for preparing electrospun fibers with a high content of a bioadhesive substance
The present invention relates to a method for preparing electrospun fibers, the method comprising v) dissolving a fiber-forming hydrophilic polymer in an alcohol selected from C1-C3 alcohols, vi) dissolving a bioadhesive substance in water, wherein the bioadhesive substance has a solubility in water of 3 g/100 ml or more at 25° C. or g/100 ml or more at 25° C., and wherein the bioadhesive substance has a solubility in an alcohol selected from C1-C3 alcohols of 0.5 g/100 nil 10 or less at 25° C. or 0.1 g/100 ml or less at 25° C., vii) adding under stirring the resulting solution from ii) to the resulting solution from i), whereby the bioadhesive substance precipitates and a homogeneous suspension is formed, wherein the bioadhesive substance is suspended as particles, and viii) electrospinning the homogeneous suspension to obtain hydrophilic fibers.
1. A layered pharmaceutical composition comprising:
a hydrophilic electrospun fiber layer, wherein the hydrophilic electrospun fibers comprise:
clobetasol propionate;
polyvinylpyrrolidone;
an ammonio methacrylate copolymer type B; and
about 35% to about 60% by weight polyethylene oxide (PEO) having a molecular weight of about 100,000 to about 400,000 daltons, and
a hydrophobic layer comprising poly(caprolactone),
wherein the hydrophilic electrospun fibers are formed by electrospinning a homogenous mixture of the clobetasol propionate, polyvinylpyrrolidone, ammonio methacrylate copolymer type B, and polyethylene oxide (PEO) in a C 1 -C 3 alcohol containing 20-50% w/w water.
2. The layered pharmaceutical composition of claim 1 , wherein the weight average molecular weight of the polyvinylpyrrolidone is about 900,000 Da to about 3,000,000 Da.
3. The layered pharmaceutical composition of claim 1 , wherein the weight average molecular weight of the polyvinylpyrrolidone is about 1,500,000 Da.
4. The layered pharmaceutical composition of claim 1 , wherein the amount of polyvinylpyrrolidone and ammonio methacrylate copolymer type B in the hydrophilic electrospun fiber layer is about 50% to about 65% by weight.
5. The layered pharmaceutical composition of claim 1 , wherein the amount of polyvinylpyrrolidone and ammonio methacrylate copolymer type B in the hydrophilic electrospun fiber layer is about 45% to about 65% by weight.
6. The layered pharmaceutical composition of claim 1 , wherein the amount of polyethylene oxide in the hydrophilic electrospun fiber layer is at least about 40% by weight.
7. The layered pharmaceutical composition of claim 1 , wherein the amount of polyethylene oxide in the hydrophilic electrospun fiber layer is about 40% to about 55% by weight.
8. The layered pharmaceutical composition of claim 1 , wherein the polyethylene oxide has a molecular weight of about 200,000 daltons.
9. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 40% to about 65% by weight polyvinylpyrrolidone (PVP) and an ammonio methacrylate copolymer type B; and
about 35% to about 60% by weight polyethylene oxide having a molecular weight of about 100,000 to about 400,000 daltons.
10. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 45% to about 65% by weight polyvinylpyrrolidone (PVP) and an ammonio methacrylate copolymer type B; and
about 35% to about 55% by weight polyethylene oxide having a molecular weight of about 100,000 to about 400,000 daltons.
11. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 45% to about 60% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 40% to about 55% by weight polyethylene oxide having a molecular weight of about 100,000 to about 400,000 daltons.
12. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 40% to about 60% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 40% to about 60% by weight polyethylene oxide having a molecular weight of about 100,000 to about 400,000 daltons.
13. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 40% to about 65% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 35% to about 60% by weight polyethylene oxide having a molecular weight of about 200,000 daltons.
14. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 45% to about 65% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 35% to about 60% by weight polyethylene oxide having a molecular weight of about 200,000 daltons.
15. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 45% to about 60% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 40% to about 55% by weight polyethylene oxide having a molecular weight of about 200,000 daltons.
16. The layered pharmaceutical composition of claim 1 , wherein the hydrophilic electrospun fiber layer comprises:
clobetasol propionate;
about 40% to about 60% by weight polyvinylpyrrolidone and an ammonio methacrylate copolymer type B; and
about 40% to about 60% by weight polyethylene oxide having a molecular weight of about 200,000 daltons.
17. The layered pharmaceutical composition of claim 1 , wherein the C 1 -C 3 alcohol is ethanol.
18. The layered pharmaceutical composition of claim 1 , wherein the C 1 -C 3 alcohol contains about 50% w/w water.
19. The layered composition of claim 1 , wherein the PEO is evenly distributed in the hydrophilic electrospun fibers.