Oral eliglustat transmucosal delivery system

Inventors

Ahmed, Salah U. • Zu, Yanming • Chowdhury, Tahseen A. • MUNTAZIM, Saad • SYED, Mohammed Irfan

Assignees

Abon Pharmaceuticals LLC

Abstract

The present disclosure relates to an oral eliglustat transmucosal delivery system. More specifically, the present disclosure is related to an oral transmucosal dosage form comprising a non-disintegrating solid mass comprising (a) a hydrophilic viscosity modifying agent selected from a natural or a synthetic gum with a molecular weight of 10,000 Daltons or greater, (b) a low molecular weight water soluble component with a molecular weight of less than 10,000 Daltons and (c) not more than 70 mg eliglustat, wherein the dosage form is 500 mg or less and provides an oral cavity residence time of at least about 5 minutes, and wherein the dosage form generates a microenvironment inside the oral cavity exhibiting a thixotropic behavior with viscosities of at least 50 poises at 1/sec shear rate and at least 10 poises at 10/sec share rate. The dosage forms of as described herein have at least 30% dose reduction as compared to commercially available eliglustat capsules. In addition, unlike the dosing prerequisite for commercially available eliglustat capsules, the oral eliglustat transmucosal dosage form described herein can be administered to patients with Gaucher disease type 1 without pre-determination of patients' CYP2D6 genotype.

Core Innovation

The invention relates to an oral transmucosal dosage form for eliglustat that includes a non-disintegrating solid mass. The dosage form comprises at least two hydrophilic viscosity modifying agents selected from a natural or synthetic gum with a molecular weight of 10,000 Daltons or greater, together with a low molecular weight water soluble component with a molecular weight of less than 10,000 Daltons. The eliglustat content is limited to not more than 70 mg, and the dosage form is 500 mg or less.

The invention generates a microenvironment inside the oral cavity that exhibits thixotropic behavior. The microenvironment is defined by viscosities of at least 50 poises at 1/sec shear rate and at least 10 poises at 10/sec shear rate. In addition, the dosage form provides an oral cavity residence time in a subject of at least about 5 minutes.

A second aspect defines the eliglustat oral transmucosal dosage form with non-disintegrating solid mass including eliglustat, at least two hydrophilic viscosity modifying agents, and at least one water soluble component. The hydrophilic viscosity modifying agents are selected from natural gums, synthetic gums, or combinations thereof, and the dosage form further contains 1-40% by weight of Eliglustat as free base or salt form(s) while maintaining the thixotropic microenvironment viscosity thresholds within the subject’s oral cavity.

Claims Coverage

The independent claims are clm-00001 and clm-00015. Across these claims, there are two main inventive feature sets: an oral cavity microenvironment defined by thixotropic viscosity thresholds and residence time, and a dosage form defined by selected hydrophilic viscosity modifying agents together with dosage and eliglustat-content constraints.

The claim set covers an oral eliglustat transmucosal, non-disintegrating solid mass that uses at least two hydrophilic viscosity modifying agents plus a low-molecular-weight water-soluble component to generate an oral-cavity thixotropic microenvironment meeting viscosity thresholds at 1/sec and 10/sec shear rates, with an oral cavity residence time of at least about 5 minutes. The second independent claim further constrains the viscosity-modifying agents by listing specific natural and synthetic gums and constrains eliglustat content to 1-40% by weight while maintaining the same thixotropic microenvironment requirements.

Stated Advantages

Documented Applications