Controlled release formulations
Inventors
Maggio, Edward T. • Meezan, Elias • Pillion, Dennis J. • Morgan, Sarah L. • Baggott, Joe
Assignees
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Publication Number
US-8329220-B2
Publication Date
2012-12-11
Expiration Date
Abstract
The present invention provides stable, self-assembling, biocompatible and biodegradable hydrogel formulations, into which one or more compounds may be incorporated allowing for delayed release or controlled release of the incorporated compounds as the hydrogel is degraded in the body.
Core Innovation
The invention relates to controlled-release, self-assembling biodegradable hydrogels that entrap therapeutic agents for delayed release. The hydrogels are formed from alkylglycosides and sucrose esters, including sucrose stearate and sucrose distearate, by heat treatment of a suspension of the components at temperatures of 37–45°C. The buffered hydrogels contain a buffer and a therapeutic agent.
The hydrogels provide thermal and enzymatic degradation features that enable delayed release. Release behavior depends on thermolability at about 37–45°C and on enzymatic degradation by glycosidases and enzymes such as esterases, lipases, or related enzymatic activity. Bilayer or multilayer hydrogel formulations are described to achieve differential release from different layers.
A bilayer hydrogel can include a temperature-sensitive alkylglycoside layer and a more thermostable sucrose-ester layer to produce rapid release from one layer and delayed release from another layer. The buffered hydrogel formulations include acetate buffer options, preservative options, and defined pH ranges, and they are presented alongside delivery-route concepts including transdermal and intranasal/pulmonary delivery, including methods for increasing mucosal residence time.
Claims Coverage
The independent claim covers one inventive feature set centered on a buffered hydrogel formed by heat treatment at 37–45°C. Dependent refinements add pH, preservative, therapeutic agent class, anti-wrinkle agent, and uniform distribution features.
Buffered hydrogel with sucrose ester combination formed by heat treatment
A buffered hydrogel comprising a therapeutic agent, a sucrose ester wherein the sucrose ester is a combination of sucrose stearate and sucrose distearate, and a buffer, wherein the hydrogel is formed by heat treatment of a suspension of (a)–(c) at temperatures of 37–45°C.
pH-constrained buffered hydrogel
The hydrogel has a pH from 4 to 8.
Preservative selection for buffered hydrogel
The hydrogel uses a preservative selected from EDTA, benzalkonium chloride, sodium azide, or dodecyl maltoside.
Therapeutic agent category selection
A therapeutic agent is selected from peptide, hormone, steroid, anti-inflammatory, anti-biotic, anti-viral, UV blocker, or anti-wrinkle agent.
Anti-wrinkle agent list for hydrogel
The anti-wrinkle agent is selected from a specified list of cosmetic actives including retinoids such as retinol and retinoic acid, hydroxy acids and exfoliants such as glycoic acid, lactic acid and alpha/beta hydroxy acid classes, a Coenzyme Q10 copper peptide, kinetin, tea extract, and collagen.
Uniform distribution of therapeutic agent
The therapeutic agent is uniformly distributed throughout the hydrogel.
The claim coverage centers on a buffered hydrogel that includes a therapeutic agent, a sucrose stearate/sucrose distearate combination, and a buffer, with formation by heat treatment at 37–45°C. Dependent features further constrain pH, preservative selection, therapeutic agent class, anti-wrinkle agent selection, and uniform distribution throughout the hydrogel.
Stated Advantages
Controlled-release with delayed release of entrapped therapeutic agents.
Differential release via bilayer or multilayer formulations enabling different release behaviors from different layers.
Stability of acetate-buffered gels for extended storage.
Uniform distribution of the therapeutic agent throughout the hydrogel.
Documented Applications
Use in rheumatoid arthritis, including bilayer hydrogel concepts involving methotrexate and folic acid/folate.
Intranasal delivery use case described as involving intranasal methylene blue for Alzheimer’s disease.
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