Invention for Immediate Release Composition Resistant to Abuse by Intake of Alcohol

Invented by Peter Holm Tygesen, Jan Martin Oevergaard, Joakim Oestman, Egalet Ltd

The abuse of alcohol is a significant problem around the world, with millions of people suffering from alcohol addiction and related health issues. One of the most significant challenges in addressing this problem is the development of effective strategies to prevent alcohol abuse. One promising approach is the use of Immediate Release Composition (IRC) that is resistant to abuse by intake of alcohol.

IRC is a type of medication that is designed to release its active ingredients quickly, providing rapid relief to patients suffering from various conditions. However, the rapid release of these ingredients can also make IRC susceptible to abuse by individuals who want to experience the effects of the medication quickly. One way to prevent this abuse is to develop IRC that is resistant to the effects of alcohol.

The market for IRC resistant to abuse by intake of alcohol is growing rapidly, driven by the increasing demand for effective strategies to prevent alcohol abuse. This market includes a wide range of products, including pain relievers, cough suppressants, and other medications that are commonly abused by individuals who want to experience their effects quickly.

One of the key drivers of this market is the growing awareness of the dangers of alcohol abuse. Many people are now aware of the risks associated with excessive alcohol consumption, including liver damage, heart disease, and other serious health problems. As a result, there is a growing demand for medications that are resistant to the effects of alcohol, as these products can help prevent alcohol abuse and reduce the risk of related health problems.

Another important factor driving the market for IRC resistant to abuse by intake of alcohol is the increasing availability of these products. Many pharmaceutical companies are now developing IRC that are resistant to the effects of alcohol, and these products are becoming more widely available in pharmacies and other retail outlets. This increased availability is making it easier for individuals to access these medications and use them as part of their overall strategy to prevent alcohol abuse.

In conclusion, the market for IRC resistant to abuse by intake of alcohol is a rapidly growing and important segment of the pharmaceutical industry. As the awareness of the dangers of alcohol abuse continues to grow, the demand for these products is likely to increase, and we can expect to see continued innovation and development in this area in the years to come. Ultimately, the development of effective strategies to prevent alcohol abuse is essential to improving public health and reducing the burden of alcohol-related health problems around the world.

The Egalet Ltd invention works as follows

The present invention is a composition for immediate release that can be administered orally and which resists abuse due to alcohol intake. This disclosure provides immediate-release pharmaceutical compositions that include a polyglycol with a molecular mass of between about 900 and about 17,000 daltons. The compositions also contain a drug, one or two effervescent substances, or disintegrants.

Background for Immediate Release Composition Resistant to Abuse by Intake of Alcohol

In recent years, abuse of OTC and prescription pharmaceuticals has been a growing concern. In some cases, abusers will combine prescription and over-the counter pharmaceuticals with alcohol to enhance the effects of alcohol or the drug substance contained in the product. Certain pharmaceutical products intended for oral administration release their drug substances at a higher rate when alcohol is present. This means that the drug substance can be absorbed at a rate faster than the manufacturer intended. This faster release rate can lead to undesirable and potentially dangerous side effects.

The unintended release of a large amount of drug substance within a pharmaceutical formulation over a short time period is commonly referred to by the term “dose dumping”. Some compositions, which often contain relatively large amounts of drug substance to maintain a therapeutic effect over a long period of time (e.g. sustained or controlled-release pharmaceutical formulations), have been found to contain excipients and drug substances that are more soluble in ethanolic solution than in aqueous, non-ethanolic solutions. These compositions may exhibit high rates of dissolution of the drug and higher release rates in the presence ethanol. Consuming alcoholic beverages with modified-release formulations that show increased release rates of drug substances in the presence ethanol can induce dose dumping. This may make it easier to abuse such modified-release preparations. The potential problems caused by dose dumping when ethanol is present are not restricted to modified-release formulations. In the presence of alcohol, conventional oral compositions, such as immediate-release compositions, may exhibit dose dumping behavior. This can lead to a more rapid uptake and delivery of the drug.

In the 1990s the U.S. Food and Drug Administration required that some OTC pain relievers and temperature reducers have a warning label, advising consumers to consult with a doctor before using these products if they consume three or more alcohol drinks per day. FDA released this final rule following public comments and data regarding the effects of chronic alcohol consumption and the use various OTC pain relievers. This action was also taken in response to the Nonprescription Drugs Advisory Committee as well as the Arthritis Drugs Advisory Committee’s recommendations that chronic alcohol consumers should be informed that there is a risk that these drugs could cause liver damage or stomach bleeds. This labeling requirement affects drug substances such as aspirin, acetaminophen and other salicylates. It also includes ibuprofen and naproxen sodium.

FIGURES

FIG. 1. PEG 3350S is available without disintegrant and effervescence. Dissolution profiles % release against time (n=3) (n=3) for HCl buffer solution (pH1.2) and alcohol 40% (v/v/pH1.2).

FIG. 2. PEG 6000 is available without disintegrant and effervescence. Dissolution profiles % release against time (n=3) (n=3) using HCl (pH1.2) solution and 40% (v/v/pH1.2) alcohol.

FIG. 3. PEG 17,000 with no disintegrant. Dissolution profiles % release against time (n=3) (n=3), in HCl (pH1.2) solution and 40% (v/v/pH1.2) alcohol.

FIG. 4. PEG 3350 effervescent with a mixture of 2% citric and 5% NaHCO3. Dissolution profiles % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 5. PEG 6000 in combination with NaHCO3 and 2% citric acids as an effervescent. Dissolution profiles % release against time (n=3) and 40% alcohol/pH1.2.

FIG. 6. PEG 17,000 with NaHCO3 and 4% citric acids as an effervescent. Dissolution profiles % release against time (n=3) (in minutes) in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 7. PEG 6000 disintegrated with 10% Cross-caramellose NA. Dissolution profiles % release against time (n=3) and 40% alcohol (v/v/pH1.2).

FIG. 8. PEG 17,000 containing 4% citric and 10% NaHCO3 for effervescent agents and 5% Cross-caramellose Na to disintegrate. Dissolution profiles % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 9. PEG 14,000 containing 3% citric and 7.5% NaHCO3 for effervescence and 12.5% Cross-caramellose Na to disintegrate. Dissolution profiles % release against time (n=3) (in minutes) in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 10. PEG 10,000 containing a mixture of 2.5% citric and 6.25% NaHCO3 for effervescence and 12.5% Cross Caramellose Na to disintegrate. Dissolution profiles % release against time (n=3) (in minutes) in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 11. PEG 6000 with a mixture of 2% citric and 5% NaHCO3 for effervescent agents and 12.5% Cross Caramellose Na (as disintegrant). Dissolution profiles % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 12. PEG 3350 containing a mixture of 2% citric and 5% NaHCO3 for effervescence and 12.5% Cross Caramellose Na to disintegrate. Dissolution profiles % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v), alcohol/pH1.2.

FIG. 13. PEG 6000 in combination with 5% NaHCO3 and 2% tartaric acids as an effervescent. No disintegrant was added. “Dissolution-profiles: % release against time in minutes in HCl (pH1.2) solution and 40% (v/v/v/v/v/v/v/v/v/v/v/v/v/v/v/v alcohol/pH1.2.

FIG. 14. PEG 6000, with the addition of 4% tartaric and 5% NaHCO3 to act as an effervescent. No disintegrant was added. “Dissolution-profiles: % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v/pH1.2) alcohol.

FIG. 15. PEG 6000 in combination with added 2% succinic and 5% NaHCO3 for effervescent agents. No disintegrant was added. “Dissolution-profiles: % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v/%) alcohol/pH1.2.

FIG. 16. PEG 6000 combined with malonic acid 4% and NaHCO3 5% as an effervescent. No disintegrant was added. “Dissolution-profiles: % release against time in minutes in HCl (pH1.2) solution and 40% (v/v/a) alcohol/pH1.2.

FIG. 17. PEG 6000 effervescent with the addition of 4% benzoic and 5% NaHCO3 No disintegrant was added. “Dissolution-profiles: % release against time (n=3) (in HCl (pH1.2) solution and 40% (v/v/v/v/v/v/v/v/v/v/v/v/v/v/v/v alcohol/pH1.2).

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