Formulation for oral delivery of proteins, peptides and small molecules with poor permeability
The present disclosure is directed to a pharmaceutical formulation intended for oral delivery of synthetic or natural poorly permeable molecules or salts/solvates thereof having a therapeutic activity. The pharmaceutical formulation can include a synthetic or natural poorly permeable molecule or salt or solvate thereof in an amount 0.01-10 wt. % of the total weight of the formulation; a lipophilic phase comprising triglycerides of fatty acids in an amount of 50-80 wt. % of the total weight of the formulation; and at least one lipophilic surfactant comprising partial esters of polyol and fatty acids in an amount of about 10-50 wt. % of the total weight of the formulation.
1 . A pharmaceutical formulation, comprising:
a dispersed powder suspended in the pharmaceutical formulation, the dispersed powder comprising an active pharmaceutical ingredient comprising a synthetic or natural poorly permeable peptide having 5 to 20 amino acids or salt or solvate thereof in an amount of 0.01-5 wt. % of the total weight of the formulation;
a lipophilic phase comprising triglycerides of fatty acids; and
at least one lipophilic surfactant comprising partial esters of polyol and fatty acids,
wherein the pharmaceutical formulation is free of polysaccharides and is a water-free reverse emulsion.
2 . The formulation of claim 1 , further comprising at least one hydrophilic surfactant with a hydrophilic lipophilic balance (“HLB”) above 10.
3 . The formulation of claim 2 , wherein the at least one hydrophilic surfactant is selected from the group consisting of polyoxyethylene (20) monooleate, PEG 8 caprylic/capric glycerides, PEG 6 caprylic/capric glycerides, poly(oxyethylene)(4)Lauryl ether and mixtures thereof.
4 . The formulation of claim 1 , wherein the triglycerides of fatty acids are medium chain fatty acids.
5 . The formulation of claim 1 , wherein the at least one lipophilic surfactant comprises a mixture of mono and diglyceride of medium chain fatty acids.
6 . A delayed release pharmaceutical dosage form comprising:
a pharmaceutical formulation comprising:
a dispersed powder suspended in the pharmaceutical formulation, the dispersed powder comprising an active pharmaceutical ingredient comprising a synthetic or natural poorly permeable peptide having 5 to 20 amino acids or salt or solvate thereof in an amount of 0.01-5 wt. % of the total weight of the formulation;
a lipophilic phase comprising triglycerides of fatty acids; and
at least one lipophilic surfactant comprising partial esters of polyol and fatty acids, wherein the delayed release dosage form is a coated dosage form whose release is pH dependent and the pharmaceutical formulation is free of polysaccharides and is a water-free reverse emulsion.
7 . A method for treating a patient, comprising administering to a person in need thereof an effective amount of a pharmaceutical formulation comprising:
a dispersed powder suspended in the pharmaceutical formulation, the dispersed powder comprising an active pharmaceutical ingredient comprising a synthetic or natural poorly permeable peptide having 5 to 20 amino acids or salt or solvate thereof in an amount of 0.01-5 wt. % of the total weight of the formulation;
a lipophilic phase comprising triglycerides of fatty acids; and
at least one lipophilic surfactant comprising partial esters of polyol and fatty acids,
wherein the pharmaceutical formulation is free of polysaccharides and is a water-free reverse emulsion.
8 . The method of claim 7 , wherein the pharmaceutical composition further comprises at least one hydrophilic surfactant with a hydrophilic lipophilic balance (“HLB”) above 10.
9 . The method of claim 8 , wherein the at least one hydrophilic surfactant is selected from the group consisting of polyoxyethylene (20) monooleate, PEG 8 caprylic/capric glycerides, PEG 6 caprylic/capric glycerides, poly(oxyethylene)(4)Lauryl ether and mixtures thereof.
10 . The method of claim 7 , wherein the triglycerides of fatty acids are medium chain fatty acids.
11 . The formulation of claim 7 , wherein the at least one lipophilic surfactant comprises a mixture of mono and diglyceride of medium chain fatty acids.
12 . The method of claim 7 , wherein the pharmaceutical formulation is in a delayed release dosage form comprising a coated dosage form whose release is pH dependent.
13 . The formulation of claim 1 , wherein the lipophilic phase comprising triglycerides of fatty acids is in an amount of 50-80 wt. % of a total weight of the formulation.
14 . The formulation of claim 13 , further comprising at least one hydrophilic surfactant with a hydrophilic lipophilic balance (“HLB”) above 10.