Pharmaceuticals for oral delivery
Inventors
Carl, Stephen M. • Vrettos, John Stanley • Stern, William
Assignees
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Publication Number
US-9457086-B2
Publication Date
2016-10-04
Expiration Date
Abstract
The present invention provides solid oral dosage forms and methods of treating subjects in need thereof. The solid oral dosage forms of the present invention provide a mixture including at least one compound classified as BCS Class II, BCS Class III or BCS Class IV, where the compound does not include a peptide bond in the compound's molecular structure; an absorption enhancer; and coated organic acid particles; an enteric coating; and a water soluble barrier positioned between the mixture and the enteric coating.
Core Innovation
The invention relates to a solid oral dosage form comprising a mixture of at least one active pharmaceutical compound classified as BCS Class III, where the compound does not include a peptide bond in its molecular structure. The dosage form includes functional excipients consisting of an absorption enhancer and coated citric acid particles, the citric acid particles being coated with a water soluble coat that separates the citric acid from the active pharmaceutical compound.
The dosage form additionally includes an enteric coating and a water soluble barrier positioned between the mixture and the enteric coating, thereby separating the mixture from the enteric coating. If the dosage form is added to ten milliliters of 0.1 M aqueous sodium bicarbonate solution, the pH of the solution is lowered to no higher than 5.5.
When administered orally, the solid dosage form provides a synergistic increase in systemic bioavailability compared to administration of a solid dosage form containing an equal dose of the active pharmaceutical compound without the functional excipients. In embodiments, the synergistic increase is about a 4-fold to about a 7-fold increase in mean systemic bioavailability as measured in a Beagle dog model.
Claims Coverage
The consolidated content includes five independent claims. Across them, the core claim coverage centers on a solid oral dosage form with functional excipients consisting of an absorption enhancer and coated citric acid particles, plus an enteric coating and a water soluble barrier, with pH-lowering behavior in 0.1 M aqueous sodium bicarbonate and a synergistic increase in systemic bioavailability versus an equal-dose comparator without the functional excipients.
Solid oral dosage form with absorption enhancer and coated citric acid particles separated by water soluble coat, enteric coating, and water soluble barrier
A solid oral dosage form comprising a mixture of at least one BCS Class III active pharmaceutical compound without a peptide bond, functional excipients consisting of an absorption enhancer and coated citric acid particles coated with a water soluble coat that separates citric acid from the active pharmaceutical compound, an enteric coating, and a water soluble barrier positioned between the mixture and the enteric coating, wherein if added to ten milliliters of 0.1 M aqueous sodium bicarbonate solution the pH is lowered to no higher than 5.5, and oral administration provides a synergistic increase in systemic bioavailability versus an equal dose without the functional excipients.
Solid oral dosage form with lauroyl-carnitine and coated citric acid particles for synergistic bioavailability increase
A solid oral dosage form comprising a mixture of at least one antibiotic or antiviral compound classified as BCS Class III without a peptide bond, functional excipients consisting of lauroyl-carnitine and coated citric acid particles coated with a water soluble coat separating citric acid from the antibiotic or antiviral compound, an enteric coating, and a water soluble barrier positioned between the mixture and the enteric coating, wherein addition to ten milliliters of 0.1 M aqueous sodium bicarbonate lowers pH to no higher than 5.5, and oral administration provides a synergistic increase in systemic bioavailability versus an equal dose without the functional excipients.
Method for enhancing systemic bioavailability by orally administering the solid oral dosage form
A method for enhancing the systemic bioavailability of a therapeutically effective amount of at least one BCS Class III active pharmaceutical compound without a peptide bond to a subject in need thereof, comprising orally administering a solid oral dosage form having functional excipients consisting of an absorption enhancer and coated citric acid particles coated with a water soluble coat, an enteric coating, and a water soluble barrier between the mixture and the enteric coating, wherein addition to ten milliliters of 0.1 M aqueous sodium bicarbonate lowers pH to no higher than 5.5, and oral administration results in a synergistic increase in systemic bioavailability versus an equal dose without the functional excipients.
Method of treating bacterial or viral infection with orally administered BCS Class III solid oral dosage form
A method of treating a bacterial or viral infection in a subject in need thereof comprising orally administering a solid oral dosage form comprising a mixture of at least one BCS Class III active pharmaceutical, antibacterial, or antiviral compound without a peptide bond and functional excipients consisting of an absorption enhancer and coated citric acid particles coated with a water soluble coat, an enteric coating, and a water soluble barrier positioned between the mixture and the enteric coating, wherein addition to ten milliliters of 0.1 M aqueous sodium bicarbonate lowers pH to no higher than 5.5, and oral administration results in a synergistic increase in systemic bioavailability versus an equal dose without the functional excipients.
Solid oral dosage form providing about a 4-fold to about a 7-fold increase in mean systemic bioavailability in Beagle dogs
A solid oral dosage form comprising a mixture of at least one BCS Class III active pharmaceutical compound without a peptide bond, an absorption enhancer, coated citric acid particles coated with a water soluble coat that separates citric acid from the active compound and lowers pH to no higher than 5.5 when added to ten milliliters of 0.1 M aqueous sodium bicarbonate, an enteric coating, and a water soluble barrier positioned between the mixture and the enteric coating, wherein oral administration provides about a 4-fold to about a 7-fold increase of the mean systemic bioavailability of the active pharmaceutical compound compared with an equal dose solid dosage form without the absorption enhancer and the coated citric acid particles as measured in a Beagle dog model.
Overall, the claim coverage is directed to oral formulations that combine BCS Class III actives lacking peptide bonds with an absorption enhancer and coated citric acid particles having a water soluble coat, plus an enteric coating separated by a water soluble barrier, and that exhibit pH lowering to no higher than 5.5 in 0.1 M aqueous sodium bicarbonate while producing a synergistic systemic bioavailability increase versus an equal-dose formulation lacking the functional excipients. A further independent claim specifies about a 4-fold to about a 7-fold mean bioavailability increase measured in a Beagle dog model.
Stated Advantages
Synergistic increase in systemic bioavailability when administered orally compared to an equal dose without the functional excipients.
About a 4-fold to about a 7-fold increase of mean systemic bioavailability in comparison to an equal dose solid dosage form without the absorption enhancer and coated citric acid particles, as measured in a Beagle dog model.
Documented Applications
Enhancing systemic bioavailability of a therapeutically effective amount of at least one BCS Class III active pharmaceutical compound to a subject in need thereof.
Treating a bacterial or viral infection in a subject in need thereof by orally administering the solid oral dosage form.
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