Stable intranasal formulations of carbetocin

Abstract

The application describes stable aqueous compositions comprising relatively high concentrations of carbetocin and a solubilizer and / or surface active agent. The disclosed carbetocin compositions are effective in the treatment of a neurodevelopmental disorder, such as Präder-Willi syndrome. Additionally, the disclosed carbetocin compositions show improved stability at room temperature and / or under accelerated conditions of stress.

Description

DESCRIPTION OF THE DISCLOSURE[0001]This application claims priority from U.S. Provisional Patent Application No. 62 / 734,152, filed Sep. 20, 2018, and U.S. Provisional Patent Application No. 62 / 876,857, filed Jul. 22, 2019, both of which are hereby incorporated by reference in their entirety.FIELD OF THE DISCLOSURE[0002]The present disclosure relates to stable intranasal pharmaceutical preparations of carbetocin, including those that demonstrate improved stability under various long-term storage conditions and / or under accelerated conditions of stress. The present disclosure also relates to methods of preparing such pharmaceutical preparations. The present disclosure further relates to kits and the use of the intranasal pharmaceutical preparations for the treatment of neurodevelopmental disorders, such as Präder-Willi syndrome, and related symptoms.BACKGROUND OF THE DISCLOSURE[0003]Although both peptides and proteins are composed of amino acids, peptides are typically distinguished f...

AI Technical Summary

Benefits of technology

The patent text describes a pharmaceutical preparation of carbetocin for the treatment of neurodevelopmental disorders, specifically Präder-Willi syndrome. Carbetocin is a peptide with a shorter amino acid sequence than peptides, but it is still considered a peptide because of its size. The pharmaceutical preparation can be administered nasally or through injection. The text also describes the stability and bioavailability of the pharmaceutical preparation. The technical effect of the patent is to provide a more effective and tolerable treatment for neurodevelopmental disorders.

Problems solved by technology

Depending on potency, it may be necessary to formulate a peptide at a high concentration, but doing so may increase the likelihood of peptide aggregation.

But for peptides without ionizable groups, pH optimization may not be possible.

Consequently, maintaining a sufficient stability at high peptide concentrations may be challenging, especially since peptides generally do not possess higher-order structure, and their physical stability thus primarily depends on the nature of their peptide-peptide interactions.

It is also known that carbetocin lacks a stable and well-defined tertiary structure.

Other prior attempts to develop a heat-stable oxytocin formulation for injection have been unsuccessful.

Other attempts have been made to make stable high carbetocin formulations using typical peptide excipients (e.g., surfactants); however, none of the studied excipients prevented carbetocin aggregation.

In addition, when aqueous carbetocin solutions are manufactured, packaged, transported, stored, and handled prior to administration to a patient, they are subject to mechanical and chemical stresses.

These types of stresses can be detrimental to various formulations of carbetocin in solution.

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