US-20260124141-A1 - TAMPER-RESISTANT PHARMACEUTICAL COMPOSITIONS OF OPIOIDS AND OTHER DRUGS

Abstract

Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.

Inventors

• Roman Rariy
• Alison Fleming
• Jane C. Hirsh
• Said Saim
• Ravi K. Varanasi

Assignees

• COLLEGIUM PHARMACEUTICAL, INC.

Dates

Publication Date

20260507

Application Date

20250611

Claims (20)

1. 1 . A pharmaceutical composition comprising a plurality of multiparticulates each multiparticulate comprising: (a) one or more drugs prone to abuse; and (b) one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof; wherein the one or more drugs interact ionically with one or more of the excipients.
2. 2 . The composition of claim 1 , wherein said drug is soluble in said one or more excipients when the one or more excipients are in their molten state.
3. 3 . The composition of claim 1 , wherein the composition is a solid solution.
4. 4 . The composition of claim 1 , wherein said plurality of multiparticulates have a span of less than 5.
5. 5 . The composition of claim 1 , wherein said plurality of multiparticulates have a D(0.5) of less than about 750 μm.
6. 6 . The composition of claim 1 , wherein said drug prone to abuse is an opioid analgesic.
7. 7 . The composition of claim 1 , wherein the one or more excipients that interact ionically with said drug(s) are fatty acids.
8. 8 . The composition of claim 1 , wherein the composition retards the release of a portion of the drug prone to abuse even if the physical integrity of the composition is compromised and the compromised composition is exposed to water.
9. 9 . The composition of claim 1 further comprising one or more anti-oxidants.
10. 10 . The composition of claim 1 , wherein the one or more excipients have a low peroxide content in order to reduce oxidation of the drug or excipients.
11. 11 . The composition of claim 10 , wherein the one or more excipients comprises carnauba wax having a peroxide value of less than 25 ppm.
12. 12 . The composition of claim 11 , wherein the carnauba wax has a peroxide value of less than 5 ppm.
13. 13 . The composition of claim 11 , wherein the carnauba wax has a peroxide value of less than 3 ppm.
14. 14 . The composition of claim 1 , further comprising one or more substances used to change the dissolution behavior or the physical and/or chemical stability of the formulation.
15. 15 . The composition of claim 14 , wherein the one or more substances change the dissolution behavior of the formulation.
16. 16 . The composition of claim 14 , wherein the one or more substances comprises rate-controlling materials.
17. 17 . The composition of claim 16 , wherein said rate-controlling materials comprise starch derivatives, cellulose derivatives, acrylic polymers, polyvinyl pyrrolidone, alginic acid, lactose or mixtures thereof.
18. 18 . The composition of claim 14 , wherein said rate-controlling materials comprise one or more pharmaceutically acceptable surfactants.
19. 19 . The composition of claim 18 , wherein the one or more pharmaceutically acceptable surfactants comprise lecithin, sodium dodecyl sulfate, sodium salts of fatty acids, potassium salts of fatty acids, poloxamer, polyethoxylated castor oil, polyoxylglycerides, polysorbates, sorbitan stearate, or mixtures thereof.
20. 20 .- 33 . (canceled)

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 18/935,022, filed Nov. 1, 2024, which is a continuation of U.S. patent application Ser. No. 18/432,310, filed Feb. 5, 2024 (now abandoned), which is a continuation of U.S. patent application Ser. No. 18/324,834, filed May 26, 2023 (now abandoned), which is a continuation of U.S. patent application Ser. No. 17/957,831, filed Sep. 30, 2022 (now abandoned), which is a continuation of U.S. patent application Ser. No. 17/677,856, filed Feb. 22, 2022 (now abandoned), which is a continuation of U.S. patent application Ser. No. 17/369,443, filed Jul. 7, 2021 (now abandoned), which is a continuation of U.S. patent application Ser. No. 16/953,852, filed Nov. 20, 2020 (now abandoned), which is a continuation of U.S. patent application Ser. No. 16/849,750, filed Apr. 15, 2020 (now abandoned), which is a continuation of U.S. patent application Ser. No. 16/413,242, filed May 15, 2019 (now U.S. Pat. No. 10,668,060, issued Jun. 2, 2020), which is a continuation of U.S. patent application Ser. No. 16/017,097, filed Jun. 25, 2018 (now abandoned), which is a continuation of U.S. patent application Ser. No. 15/606,112, filed May 26, 2017 (now U.S. Pat. No. 10,004,729, issued Jun. 26, 2018), which is a continuation of U.S. patent application Ser. No. 14/320,086, filed Jun. 30, 2014 (now U.S. Pat. No. 9,682,075, issued Jun. 20, 2017), which is a continuation of U.S. patent application Ser. No. 12/965,572, filed Dec. 10, 2010 (now U.S. Pat. No. 8,840,928, issued Sep. 23, 2014), which claims the benefit of priority of U.S. Provisional Patent Application No. 61/285,231, filed Dec. 10, 2009, the disclosures of all of which are incorporated by reference as if fully set forth herein. FIELD OF THE INVENTION The present invention is generally in the field of pharmaceutical compositions, specifically compositions that are designed to reduce the potential for improper administration of drugs, such as those subject to abuse and methods of making thereof. BACKGROUND OF THE INVENTION Oxycodone, morphine, and other opioid analgesics are successful and therapeutically useful medications, e.g., as pain killers, when administered orally. Unfortunately, they also pose a severe threat for willful abuse due to their ability to alter mood and/or cause a sense of euphoria. Traditional sustained release formulations of such drugs, which contain a relatively large amount of drug meant to be released from the formulation over an sustained time period, are particularly attractive to abusers since the sustained release action can be destroyed by crushing or grinding the formulation. The resulting material (i.e., the crushed formulation) can no longer control the release of drug. Depending on the drug, abusers can then (1) snort the material, (2) swallow the material or (3) dissolve the material in water and subsequently inject it intravenously. The dose of drug contained in the formulation is absorbed immediately through the nasal or GI mucosa (e.g., snorting or swallowing, respectively) or is administered in a bolus to the systemic circulation (e.g., IV injection). These abuse methods result in the rapid bioavailability of relatively high doses of drug, giving the abuser a “high”. Since relatively simple methods (crushing, grinding, chewing and/or dissolution in water) can be used to transform such formulations into an abusable form, they provide virtually no deterrent to a potential abuser. For example, in recent years, there have been numerous reports of diversion and abuse of sustained release formulations of opioids such as oxycodone, oxymorphone and morphine. According to a report from the Abuse and Mental Health Services Administration, results from the 2007 National Survey on Drug Use and Health: National Findings (Rockville, MD: US Dept. of Health and Human Services), showed that in both 2006 and 2007, an estimated 5.2 million persons aged 12 or older (2.1 percent in each year) were current nonmedical users of prescription pain relievers. Additionally, from 2002 to 2007, there was an increase among young adults aged 18 to 25 in the rate of current use of prescription pain relievers, from 4.1 to 4.6 percent. Data from this survey also supports the notion that sustained-release formulations susceptible to tampering methods such as chewing, crushing and grinding likely contributes to the increasing rates of prescription pain reliever abuse. For example, in 2007, there were an estimated 554,000 new nonmedical users of OxyContin® (a sustained release formulation of the active drug oxycodone). Oxycodone is a controlled substance in Schedule II of the Controlled Substances Act (CSA), which is administered by the Drug Enforcement Administration (DEA). Despite the fact that Schedule II provides the maximum amount of control possible under the CSA for approved drug products, in practice it is difficult for law enforcement agencies to control the d