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-11998640-B2
Publication Date
2024-06-04
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 disclosure relates to pharmaceutical solid dosage forms for oral calcitonin with low water content, measured by Karl Fischer titration, and to room-temperature stability. Limiting tablet water reduces acid-catalyzed peptide degradation and water-dependent degradation, and helps preserve intact, biologically active salmon calcitonin without refrigeration.
The core approach uses calcitonin in a tablet core with coated citric acid particles and maltodextrin-coated protective-coated particles to lower intestinal pH. The tablet further includes a water-soluble barrier layer separating the core from an enteric coat, and representative barrier-layer polymers include polyvinyl alcohol-polyethylene glycol graft copolymer.
The water-soluble barrier layer is applied in an initial spray under specified time and product temperature conditions, with optional additional application to reach defined loading targets. The disclosure also specifies subsequent enteric coating of the tablet, including a tablet weight increase associated with the enteric coat.
Claims Coverage
The partial claims set includes two independent claims, covering both preparing an oral calcitonin tablet with specific blending/compression and coating steps and spray coating a tablet core with an initial water-soluble barrier layer followed by an enteric coating. Across the claims, the inventive features center on a calcitonin tablet core with specified excipients, an initial spray-applied water-soluble barrier layer under specified time and product temperature conditions, and a subsequent enteric coating.
Tablet preparation with specified excipients and water-soluble barrier spraying followed by enteric coating
Dry blending calcitonin, silicified microcrystalline cellulose, coated citric acid, copovidone, crospovidone, and magnesium stearate; compressing the blended mixture into a tablet core; applying a water-soluble barrier layer in an initial spray at a first spray rate sufficient to add approximately 0.25% (w/w) to the tablet core in about 30 minutes at an average product temperature of at least 45 C; and applying an enteric coating.
Spray coating a tablet core with initial water-soluble barrier layer addition followed by enteric coating
Providing a tablet core; applying a water-soluble barrier layer in an initial spray at a first spray rate sufficient to add approximately 0.25% (w/w) of the water-soluble barrier layer to the tablet core in about 30 minutes at an average product temperature of at least 45 C; and applying an enteric coating.
Two-stage water-soluble barrier-layer spraying using a first and second spray rate
Applying the water-soluble barrier layer for at least 30 minutes at a first spray rate, and then applying the water-soluble barrier layer again at a second, faster spray rate.
Quantified water-soluble barrier-layer loading ranges tied to spraying stages
Applying the water-soluble barrier layer at a second spray rate until a total of about 3.0% (w/w) to about 7.0% (w/w) of the water-soluble barrier layer is added to the tablet core.
Quantified enteric coating impact on tablet weight
An enteric coating increases the tablet weight by about 6% to about 8%, including the tablet core and a water-soluble barrier layer.
Overall, the claims center on producing an oral calcitonin tablet or tablet core coated by spray with a water-soluble barrier layer applied under specified time and temperature conditions, followed by an enteric coating, with dependent claims further defining two-stage spraying and quantitative barrier-layer loading and enteric coating weight increase ranges.
Stated Advantages
Room-temperature stability of oral calcitonin solid dosage forms with low water content.
Reduced acid-catalyzed peptide degradation by limiting tablet water.
Preservation of intact, biologically active salmon calcitonin.
Stability without refrigeration.
Reduced water-dependent degradation and assay loss.
Improved room-temperature stability is described in connection with low water content and controlled barrier-layer processing.
Documented Applications
Oral delivery of calcitonin using solid dosage forms in tablet form.
Spray coating a tablet core for oral delivery of calcitonin by applying a water-soluble barrier layer and an enteric coating.
Oral delivery of calcitonin using pharmaceutical solid dosage forms in the form of tablets with a tablet core, a water-soluble barrier layer, and an enteric coating.
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