Baclofen and r-baclofen gastroretentive drug delivery systems

Abstract

A biodegradable, multi-layered controlled release gastroretentive baclofen or R-baclofen dosage form which is optionally divided into a first dosage of baclofen or R-baclofen for immediate release and a second dosage of baclofen or R-baclofen for controlled release in the stomach and gastrointestinal tract of a patient, folded into a capsule which disintegrates upon contact with gastric juice and the dosage form unfolds rapidly upon contact with gastric juice. The biodegradable, multi-layered gastroretentive dosage forms of the invention provide fast onset of baclofen or R-baclofen activity with prolonged absorption and minimal undesirable side effects.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS[0001]The present application is a continuation in part of PCT Application PCT / IB2009 / 007419, filed Oct. 19, 2009, which claims priority to U.S. Provisional Patent Application No. 61 / 120,051, filed Dec. 4, 2008.FIELD OF THE INVENTION[0002]The present invention relates to biodegradable gastroretentive drug formulations for the immediate release and sustained release of baclofen. The gastroretentive baclofen or R-baclofen formulations of the invention may be orally administered to a subject in need thereof for the treatment of spasticity, spastic diplegia, alcoholism, alcohol addiction or alcohol dependence and abuse, gastro-esophageal reflux disease (GERD), emesis, cough, narcotic addiction or abuse, nicotine addiction or abuse, neuropathic pain and musculoskeletal pain, nocturnal acid breakthrough, chronic hiccups, dyspepsia, gastric motility disorder, migraine, PTSD (Post-traumatic Stress Disorder), depression, anxiety, lower urinary tr...

AI Technical Summary

Benefits of technology

[0031]In another aspect, the invention provides a method for reducing sharp peaks in the blood plasma concentration of baclofen or R-baclofen after administration of baclofen or R-baclofen to a subject in need thereof over a period of up to 24 hours and can improve therapeutic activity, which comprises orally administering to a subject in need thereof a multilayered gastroretentive dosage form of baclofen or R-baclofen.

Problems solved by technology

Stroke and traumatic brain injury (TBI) are another common cause of spasticity.

The muscles constantly rigidly contract and become permanently hypertonic, creating difficulty with voluntary and passive movement, pain and deformities.

Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord, causing loss of balance, numbness, pain, vision loss, and impairing brain functions.

Unfortunately, baclofen is associated with significant and frequent side effects.

These undesired side effects might be associated with its considerable fluctuation of blood levels.

Moreover, the drug must be administered 3 or 4 times a day, which is a drawback.

However, its usage for these indications is very limited due to its current daily regimen of 3-4 times a day administration.

This frequent dosing may result in very poor compliance among alcohol and cocaine abusers.

Baclofen and other GABAβ receptor agonists may also be used as reflux inhibitors for the prevention and treatment of gastrooesophageal reflux disease (GERD), also named “acid reflux disease.” However, the required frequent dosing and side effects of baclofen pose a problem and limit its usage.

Therefore, typical extended release formulations of baclofen cannot provide a true long-acting baclofen.

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