METHOD FOR PREPARING ELECTROSPUN FIBERS WITH A HIGH CONTENT OF A BIOADHESIVE SUBSTANCE

Abstract

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.

Claims

1-15. (canceled)

16. A layered pharmaceutical composition comprising: a hydrophilic electrospun layer comprising: clobetasol propionate; polyvinylpyrrolidone; 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, and a hydrophobic layer comprising poly(caprolactone).

17. The layered pharmaceutical composition of claim 16, wherein the weight average molecular weight of the polyvinylpyrrolidone is about 900,000 Da to about 3,000,000 Da.

18. The layered pharmaceutical composition of claim 16, wherein the weight average molecular weight of the polyvinylpyrrolidone is about 1,500,000 Da.

19. The layered pharmaceutical composition of claim 16, wherein the amount of polyvinylpyrrolidone and ammonio methacrylate copolymer type B in the hydrophilic electrospun layer is about 50% to about 85% by weight.

20. The layered pharmaceutical composition of claim 16, wherein the amount of polyvinylpyrrolidone and ammonio methacrylate copolymer type B in the hydrophilic electrospun layer is about 45% to about 70% by weight.

21. The layered pharmaceutical composition of claim 16, wherein the amount of polyethylene oxide in the hydrophilic electrospun layer is at least about 40% by weight.

22. The layered pharmaceutical composition of claim 16, wherein the amount of polyethylene oxide in the hydrophilic electrospun layer is about 40% to about 55% by weight.

23. The layered pharmaceutical composition of claim 16, wherein the polyethylene oxide has a molecular weight of about 200,000 daltons.

24. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 50% to about 85% 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.

25. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 45% to about 70% 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.

26. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 45% to about 70% 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.

27. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 50% to about 85% 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.

28. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 50% to about 85% 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.

29. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 45% to about 70% 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.

30. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 45% to about 70% 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.

31. The layered pharmaceutical composition of claim 16, wherein the hydrophilic electrospun layer comprises: clobetasol propionate; about 50% to about 85% 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.

Description

LEGENDS TO FIGURES

[0093] FIG. 1. Electrospun membranes from: A) Original recipe solution and, B) Recipe according to the invention involving precipitation of PEO.

EXAMPLES

[0094] Solution Preparation and Electrospinning Process

[0095] a) Comparative Method of Preparing the Fibers:

[0096] Weight absolute alcohol. Add slowly during stirring 6.52 wt. % Kollidon 90F and 8.15 wt. % of EudragitRS100 (of alcohol amount). Continue stirring during 24 h. Add slowly while stirring 13.05 wt. % of Polyox WSR N-80 (PEO 200,000 Mw). Keep stirring until a homogeneous suspension is created. Final mixture has 27.72% of total solids (66% of the original recipe).

[0097] Process with a single needle injector (15 G) at 2 mL/h, 10 cm of distance between the tip of the needle and the collector and 13 kV difference during 3 hours. The final membrane (fiber layer) was of 147.4 g per m.sup.2.

[0098] b) Recipe According to the Present Invention:

[0099] Weight absolute alcohol. Add slowly during stirring 8 wt. % Kollidon 90F and 10 wt. % of EudragitRS100 (of alcohol amount). Continue stirring during 24 h.

[0100] Weight distilled water. Add slowly during stirring 16 wt. % of Polyox WSR N-80 (PEG 200,000 Mw). Keep stirring during 24 h.

[0101] Add slowly alcoholic solution to water solution while stirring. Keep stirring until a homogeneous mixture is formed. Final mixture has 17% or total solids

[0102] Process with multineedle injector (56 needles 20 G) at 110 mL/h, 19 cm of distance between the tip of the needle and the collector and 60 kV difference during several hours. The final membrane (fiber layer) was of 160 per m.sup.2. A small piece of 12?5 cm was cutted for further analyses.

[0103] Membrane Morphological Characterization

[0104] Both membranes (fiber layers) were inspected by scanning electron microscopy. Samples were sputtered with a mixture of gold-palladium during 180 second and were observed in a Hitachi 54800 at an accelerating voltage of 5 kV and 8 mm of working distance.

[0105] FIG. 1 shows images of both membranes took at 1500 magnification. Samples made according to the present invention had a smaller fiber diameter mainly due to the lower total solid content and the higher difference of voltage applied. The comparative sample showed big particles of PEO between the fibers as was previously observed.