Formulations for oral administration of active agents
Inventors
Burshtein, Gregory • ROTHNER, Ariel • SCHWARTZ, Phillip M. • GALITZER, Hillel
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12239691-B2
Publication Date
2025-03-04
Expiration Date
Abstract
Pharmaceutical compositions comprising a therapeutically active agent and an absorption enhancer such as NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB or a salt thereof, for use in the treatment of a condition treatable by said therapeutically active agent, are provided. The compositions are for concomitant oral administration of two or more of the unit dosage form, which form together a therapeutically effective amount of the therapeutically active agent and an effective amount of the absorption enhancer. Multi-dose compositions comprising the two or more of the unit dosage form are also provided.
Core Innovation
The invention relates to a pharmaceutical composition multi-unit dosage form comprising at least three discrete unit dosage forms bound to one another by a coating and/or matrix. Each unit dosage form comprises a therapeutically active agent together with an absorption enhancer, and the therapeutically active agent has a molecular weight in a range of 1 kDa to 100 kDa and/or is a BCS Class III agent.
The unit dosage forms together comprise a therapeutically effective amount of the therapeutically active agent and an effective amount of the absorption enhancer. The coating and/or matrix is formulated for immediate release upon oral administration, so that the multi-unit dosage form disintegrates in gastric fluid and/or in saliva within no more than 5 minutes.
The absorption enhancer is selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts thereof. At least 50 weight percents of the unit dosage forms consists of the absorption enhancer. The described approach further includes oral treatment and kit concepts using at least three unit dosage forms that are not comprised by a multi-unit dosage form.
Claims Coverage
The independent claims cover one composition claim and treatment method and kit claims. Across these claims, the inventive features center on at least three unit dosage forms for oral administration with a specified absorption enhancer, immediate release for the multi-unit composition, and molecular weight and/or BCS Class III constraints on the therapeutically active agent.
Immediate-release multi-unit dosage form with enhancer-dominant units
A pharmaceutical composition multi-unit dosage form with at least three discrete unit dosage forms bound by a coating and/or matrix, each unit containing a therapeutically active agent and an absorption enhancer; the active agent has molecular weight 1 kDa to 100 kDa and/or is a BCS Class III agent; the multi-unit is formulated for immediate release upon oral administration so the multi-unit disintegrates in gastric fluid and/or in saliva within no more than 5 minutes; the absorption enhancer is selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts; and at least 50 weight percents of the unit dosage forms consists of the absorption enhancer.
Concomitant oral PTH treatment using less-than-200 μg per unit with enhancer
A method of treating a condition treatable by oral administration of parathyroid hormone or a fragment thereof by orally administering concomitantly at least three unit dosage forms comprising less than 200 μg of parathyroid hormone or a fragment thereof and an absorption enhancer selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts, where the at least three unit dosage forms are not comprised by a multi-unit dosage form and together comprise a therapeutically effective amount and an effective amount of the absorption enhancer.
Individually packaged sets of three or more unit dosage forms as a kit
A kit comprising a plurality of sets of at least three unit dosage forms, each set packaged individually in the kit; the unit dosage forms comprising a therapeutically active agent having molecular weight 1 kDa to 100 kDa and/or being a BCS Class III agent; and an absorption enhancer selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts, where the at least three unit dosage forms are not comprised by a multi-unit dosage form and together comprise a therapeutically effective amount of the therapeutically active agent and an effective amount of the absorption enhancer.
Concomitant oral multi-unit-free treatment using enhancer-dominant units
A method of treating a condition treatable by oral administration of a therapeutically active agent by orally administering concomitantly at least three pharmaceutical composition unit dosage forms not comprised by a multi-unit dosage form, each unit comprising the therapeutically active agent and an absorption enhancer; the therapeutically active agent has molecular weight 1 kDa to 100 kDa and/or is a BCS Class III agent; the at least three unit dosage forms together comprise a therapeutically effective amount of the therapeutically active agent and an effective amount of the absorption enhancer; the absorption enhancer is selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts; and at least 50 weight percents of the unit dosage forms consists of the absorption enhancer.
The independent claims cover an immediate-release multi-unit dosage form with at least three bound unit dosage forms, and oral treatment and kit formats that rely on at least three concomitantly administered unit dosage forms that are not comprised by a multi-unit dosage form. In all cases shown, the therapeutically active agent is constrained to 1 kDa to 100 kDa and/or BCS Class III, and the absorption enhancer is selected from NAC, NAD, 5-CNAC, 4-MOAC, 4-CNAB and salts.
Stated Advantages
Reduced inter-subject variability of Cmax/AUC compared to a single-unit dosage form with the same total composition.
In some embodiments, increased Cmax/AUC.
Documented Applications
Oral treatment of a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof using concomitantly administered unit dosage forms with the specified absorption enhancers.
Oral treatment of conditions treatable by oral administration of parathyroid hormone or a fragment thereof, including specified concomitant administration using unit dosage forms containing less than 200 μg per unit.
Use of a kit comprising individually packaged sets of at least three unit dosage forms for oral administration.
Interested in licensing this patent?