Pharmaceutical or neutraceutical formulation
View Patent ↗The invention relates to a pharmaceutical or nutraceutical formulation comprising a core, comprising an active pharmaceutical or nutraceutical ingredient, a penetration promoter and a bioavailability promoting agent, and a polymeric coating for the gastrointestinal targeted release of the active ingredient, characterized in that the bioavailability promoting agent is a pharmaceutically acceptable inhibitor of proteolytic enzymes, which increases the oral bioavailability of the active ingredient by a factor of at least five, compared to a corresponding formulation without the bioavailability promoting agent.
1. A pharmaceutical or nutraceutical formulation, comprising:
a core, comprising an active pharmaceutical or nutraceutical ingredient, a penetration promoter, a bioavailability promoting agent, and only one synchronization layer; and
a polymeric coating suitable for gastrointestinal targeted release of the active ingredient,
wherein the penetration promoter is a copolymer comprising from 30 to 80% by weight of at least one C 1 - to C 4 -alkyl ester of acrylic or of methacrylic acid, and from 70 to 20% by weight of at least one alkyl(meth)acrylate monomer having a tertiary amino group in an alkyl radical,
wherein the bioavailability promoting agent is a pharmaceutically acceptable inhibitor of a proteolytic enzyme, and
the bioavailability promoting agent is configured to increase oral bioavailability of the active ingredient by a factor of at least five, compared to a corresponding formulation without the bioavailability promoting agent.
2. The formulation of claim 1 , wherein the inhibitor of proteolytic enzymes is a Bowman-Birk inhibitor.
3. The formulation of claim 1 , wherein the active ingredient has a low permeability according to Biopharmaceutical classification system (BCS)-classes III and IV.
4. The formulation of claim 1 , further comprising:
an inhibitor capable of preventing or reducing enzymatical degradation of the active ingredient,
wherein the active ingredient is of biological origin.
5. The formulation of claim 1 , wherein the active ingredient is a protein, a peptide, a lipid, a polysaccharide, or nucleic acid.
6. The formulation of claim 1 , wherein the active ingredient is desmopressin, desmopressin acetate or desmopressin lactate.
7. The formulation of claim 1 , wherein the formulation is a multiparticulate pharmaceutical or nutraceutical formulation comprising a multitude of particles in one dosage unit.
8. The formulation of claim 7 , comprising from 10 to 1000 particles.
9. The formulation of claim 7 , wherein the particles have sizes of from 0.2 to 2 mm.
10. The formulation of claim 1 , wherein an amount of the bioavailability promoting agent in the formulation is from 0.1 to 10% by weight.
11. The formulation of claim 1 , wherein the penetration promoter is a cationic polymeric substance.
12. The formulation of claim 1 , wherein up to 90% by weight of the bioavailability promoting agent is the synchronization layer.
13. The formulation of claim 1 , wherein the polymeric coating comprises an anionic cellulosic polymer or an anionic (meth)acrylate copolymer.
14. The formulation of claim 1 ,
wherein the active ingredient is anionic,
the penetration promotor is cationic, and
the active ingredient and the penetration promoter avoid ionic interaction by an excessive amount of the penetration promotor in a mixture of both the active ingredient and the penetration promoter in one compartment of the formulation; by local separation of both the active ingredient and the penetration promoter in different compartments of the formulation; or by inclusion of a salt, an amphiphilic polymer, a hydrogen bonding non-ionic polymer, or a combination thereof in a mixture of both the active ingredient and the penetration promoter in one compartment of the formulation.
15. The formulation of claim 1 , wherein the penetration promoter is a copolymer consisting of 30 to 80% by weight of at least one C 1 - to C 4 -alkyl ester of acrylic or of methacrylic acid, and from 70 to 20% by weight of at least one alkyl(meth)acrylate monomer having a tertiary amino group in an alkyl radical.
16. The formulation of claim 1 , wherein the active ingredient is heparin or derivative thereof.
17. A method of increasing oral bioavailability of an active ingredient in a formulation, the method comprising:
including a bioavailability promoting agent in a core of a formulation in need thereof,
wherein the bioavailability promoting agent is a pharmaceutically acceptable inhibitor of proteolytic enzymes
the core further comprises the active ingredient, only one synchronization layer, and a penetration promoter,
the active ingredient is a pharmaceutical or nutraceutical ingredient,
the formulation further comprises a polymeric coating suitable for gastrointestinal targeted release of the active ingredient, and
the bioavailability promoting agent is configured to increase oral bioavailability of the active ingredient by a factor of at least five, compared to a corresponding formulation without the bioavailability promoting agent.