Room temperature stable oral calcitonin formulation
Inventors
Gilligan, James P. • Maurer, George R. • Railkar, Aniruddha M. • Bauer, Phillip • Daggs, Thomas A. • Shields, Paul P.
Assignees
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Publication Number
US-11285113-B2
Publication Date
2022-03-29
Expiration Date
Abstract
Room-temperature stable dosage forms for oral delivery of calcitonin are disclosed herein. Dosage forms for oral delivery of calcitonin with low water content are also disclosed herein. Further disclosed herein are methods for producing such room-temperature stable dosage forms and low-water content dosage forms. Methods of treatment comprising the administration of such room-temperature stable dosage forms and low-water content dosage forms are also disclosed herein.
Core Innovation
The invention relates to a pharmaceutical solid dosage form for oral delivery of calcitonin, designed to provide room-temperature stability. The dosage form uses calcitonin intermixed with coated acid particles in which a pharmaceutically acceptable protective coating separates the acid from the calcitonin in the composition, and an enteric coating is provided.
A water-soluble barrier layer separates the calcitonin intermixed with coated acid particles from the enteric coating. The solid dosage form contains no more than 2.5% (w/w) water, and low water content is identified as a key formulation constraint to support stability.
The tablet embodiment comprises salmon calcitonin intermixed with maltodextrin-coated citric acid particles, wherein the maltodextrin separates the acid from the salmon calcitonin in the composition. The tablet core includes crospovidone, copovidone, microcrystalline cellulose, and magnesium stearate, together with an enteric coating comprising methacrylic acid-ethyl acrylate copolymer (1:1) and a water-soluble barrier layer comprising polyvinyl alcohol-polyethylene glycol graft copolymer.
Claims Coverage
Two independent claims are present, directed to a pharmaceutical solid oral dosage form and a pharmaceutical tablet. Across these claims, the inventive elements include coated acid particles with a protective coating separating acid from calcitonin, an enteric coating, a water-soluble barrier layer separating the calcitonin/acid blend from the enteric coating, and a residual water limit of no more than 2.5% (w/w) water.
Coated acid particles with protective coating separating acid from calcitonin
Calcitonin intermixed with coated acid particles, wherein the coated acid particles are coated with a pharmaceutically acceptable protective coating that separates the acid from the calcitonin in the composition.
Enteric coating
An enteric coating.
Water-soluble barrier layer separating calcitonin/acid from enteric coating
A water-soluble barrier layer that separates the calcitonin intermixed with coated acid particles from the enteric coating.
Residual water limitation
The solid dosage form contains no more than 2.5% (w/w) water.
Tablet core with salmon calcitonin intermixed with maltodextrin-coated citric acid particles
A tablet core comprising salmon calcitonin intermixed with maltodextrin-coated citric acid particles, wherein the maltodextrin separates the acid from the salmon calcitonin in the composition.
Tablet core includes specific excipients
crospovidone, copovidone, microcrystalline cellulose, and magnesium stearate.
Enteric coating comprises methacrylic acid-ethyl acrylate copolymer (1:1)
An enteric coating comprising methacrylic acid-ethyl acrylate copolymer (1:1).
Water-soluble barrier layer comprises polyvinyl alcohol-polyethylene glycol graft copolymer
A water-soluble barrier layer that separates the tablet core from the enteric coating, wherein the water-soluble barrier layer comprises polyvinyl alcohol-polyethylene glycol graft copolymer.
The claims cover an oral calcitonin solid dosage form that uses coated acid particles with a protective coating to separate acid from calcitonin, together with an enteric coating and a water-soluble barrier layer that separates the calcitonin/acid blend from the enteric coating, with a residual water limit of no more than 2.5% (w/w). The tablet claim further specifies salmon calcitonin with maltodextrin-coated citric acid, defined excipients, and named enteric and barrier polymers.
Stated Advantages
Supports room-temperature stability for oral calcitonin solid dosage forms.
Provides separation between acid and calcitonin using a protective coating on the coated acid particles.
Separates the calcitonin/acid intermixed portion from the enteric coating using a water-soluble barrier layer.
Links stability outcomes to control of residual water content.
Documented Applications
Oral delivery of calcitonin in a pharmaceutical solid dosage form comprising coated acid particles, an enteric coating, and a water-soluble barrier layer with no more than 2.5% (w/w) water.
Oral delivery of calcitonin as a pharmaceutical tablet having a specified tablet core with salmon calcitonin intermixed with maltodextrin-coated citric acid particles, plus an enteric coating and a water-soluble barrier layer, with no more than 2.5% (w/w) water.
Treatment methods are described for bone-related disease selected from osteoporosis, Paget's disease, pain associated with recent vertebral fragility fracture, or hypercalcemia of malignancy.
Treatment methods are described for an inflammatory disease selected from osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), or ankylosing spondylitis (AS).
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