Mucosal bioadhesive slow release carrier for delivering active principles
View Patent ↗A mucosal bioadhesive slow release carrier comprising an active principle and devoid of starch, lactose, which can release the active principal for a duration of longer than 20 hours. This bioadhesive carrier contains a diluent, an alkali metal alkylsulfate, a binding agent, at least one bioadhesive polymer and at least one sustained release polymer, as well as a method for its preparation.
1. A prolonged release mucoadhesive formulation comprising:
an antiviral agent selected from acyclovir, valacyclovir, gancyclovir, and zidovudin;
a diluent;
an alkali metal alkyl sulfate;
a binding agent;
at least one bioadhesive polymer that allows the formulation to adhere to the oral mucosa following administration to a human patient; and
at least one sustained release polymer;
wherein the formulation is configured to release the antiviral agent to the oral mucosa from 30 minutes to at least 15 hours following administration;
wherein the formulation comprises primary granules which comprise the antiviral agent, the diluent, the alkali metal alkylsulfate, and the binding agent; and
wherein the bioadhesive polymer is dispersed in the formulation.
2. The formulation of claim 1 , which comprises no more than 5% by weight of a polyvinylpyrrolidone.
3. The formulation of claim 1 , wherein the bioadhesive polymer is not in the primary granules.
4. The formulation of claim 2 , wherein the bioadhesive polymer is not in the primary granules.
5. The formulation of claim 1 or claim 2 , wherein the alkali metal alkyl sulfate is present in an amount between 2% to 6% by weight.
6. The formulation of claim 1 or claim 2 , wherein the binding agent is in an amount between 0.5% and 5% by weight.
7. The formulation of claim 1 or claim 2 , which comprises between 0.5% and 5% by weight of a polyvinylpyrrolidone.
8. The formulation of claim 1 or claim 2 , wherein the bioadhesive polymer is natural proteins.
9. The formulation of claim 8 , wherein the natural proteins are natural milk proteins.
10. The formulation of claim 1 or claim 2 , wherein said antiviral agent is acyclovir.
11. The formulation of claim 10 , which is capable of delivering the acyclovir to the oral mucosa for a period of at least 20 hours.
12. The formulation of claim 10 , wherein the acyclovir is in an amount between 50 mg and 100 mg.
13. The formulation of claim 1 or claim 2 , which comprises:
10 mg to 200 mg of acyclovir,
1% to 75% by weight of microcrystalline cellulose,
2% to 10% by weight of sodium lauryl sulfate,
0.5% to 5% by weight of a polyvinylpyrrolidone,
10% to 40% by weight of at least one bioadhesive polymer selected from natural milk proteins and mixtures thereof, and
10% to 40% by weight of hypromellose.
14. The formulation of claim 1 or claim 2 , which comprises 50 mg or 100 mg acyclovir and following administration to the oral mucosa provides a salivary concentration of acyclovir that is greater than 22.5 ng/ml for 36 hours.
15. A method of treating a mucosal disease, comprising administering to the oral mucosal of a human patient in need thereof the formulation of any one of claim 1 or claim 2 .
16. The formulation of claim 1 , wherein the formulation is devoid of starch.
17. The formulation of claim 2 , wherein the formulation is devoid of starch.
18. The formulation of claim 1 , wherein the predominant fraction of primary granules has a diameter of less than 125 μm.
19. The formulation of claim 2 , wherein the predominant fraction of primary granules has a diameter of less than 125 μm.
20. The formulation of claim 1 , wherein the at least one bioadhesive polymer is present in 10% to 40% by weight of the formulation.
21. The formulation of claim 2 , wherein the at least one bioadhesive polymer is present in 10% to 40% by weight of the formulation.
22. The formulation of claim 20 or claim 21 , wherein the bioadhesive polymer is natural proteins.
23. The formulation of claim 22 , wherein the natural proteins are natural milk proteins.
24. The prolonged release mucoadhesive formulation of claim 1 comprising:
15% by weight microcrystalline cellulose;
4.5% by weight sodium lauryl sulfate;
0.4% by weight polyvinylpyrrolidone;
20% of at least one bioadhesive polymer selected from milk protein concentrate, pea protein, carbopol 974, and chitosan;
15% hypromellose;
1% magnesium stearate;
0.4% colloidal silica; and
50 mg of acyclovir.
25. The formulation of claim 24 , wherein the bioadhesive polymer is milk protein concentrate.
26. The prolonged release mucoadhesive formulation of claim 1 comprising:
15% by weight microcrystalline cellulose;
4.5% by weight sodium lauryl sulfate;
0.4% by weight polyvinylpyrrolidone;
20% milk protein concentrate;
15% hypromellose;
1% magnesium stearate;
0.4% colloidal silica; and
100 mg of acyclovir.
27. A method of treating a mucosal disease, comprising administering to tho oral mucosal of a human patient in need thereof the formulation of claim 5 .
28. A method of treating a mucosal disease, comprising administering to the oral mucosal of a human patient in need thereof the formulation of claim 10 .