Delivery Platform for the Tamper-Resistant Modified/Controlled Release Formulations of Narcotic/Opioid Analgesics
The market for opioid drugs, used to treat patients suffering from severe and chronic pain in the seven major markets (USA, Japan, and five European countries) was estimated to exceed $7.4 billion in 2010, dominated by oxycodone. In 2013, the U.S. opioids containing market was evaluated to $4.6 billion (IMS Health).
A major problem faced by the industry is the growing abuse and misuse of opioids by drug abusers, who extract the opioids from the drugs and achieve their immediate release. The proportion of narcotic/opioid analgesics abuse associated with emergency room admissions has more than tripled, from 6.8% in 1998 to 26.5% in 2008 (TEDS report, July 15, 2010). Narcotic/opioid analgesics abuse continues to increase as current products remain easy to abuse. In 2010, enough prescription painkillers were prescribed to medicate every American adult every 4 hours for one month (PBS 2013). The number of prescription medicine abusers in 2010 was 8.76 million, 5.1 million of which abused painkillers (drugabuse.com 2013).
Flamel’s Trigger Lock™ platform is using Micropump’s competitive advantages to allow us developing tamper-resistant modified/controlled release formulations of narcotics and other drugs susceptible to abuse:
- Micropump particles are extremely difficult to crush to extract the narcotic/opioid analgesics;
- Additional modifications tailored to prevent other less publicized methods of foiling controlled release technologies; and,
- Provides either bioequivalent or improved pharmacokinetics to marketed narcotic/opioid analgesics.
Trigger Lock™ is composed of
- Drug loaded Micropump® microparticles
Sustained Release (SR) microparticleswhich are resistant to crushing
- Viscosifying ingredient(s)
To prevent abuse by injection after extraction in a small volume of solvent
- Quenching ingredient(s)
To prevent extraction in large volumes of liquid
These ingredients are all in the size range of 150-350 µm.
The high number of microparticles per dose (>20,000) prevents easy separation of these components.
Trigger Lock SR microparticles are resistant to crushingEach microparticle retains its polymer coating which is virtually impervious to further crushing and so the narcotic/opioid analgesics remains sequestered and unobtainable and the Trigger Lock™ powder exhibits identical release characteristics as the intact, overall tablet or capsule.
The FDA’s move to restrict prescribing extended-release opioid analgesics should benefit tamper-resistant formulations, such as, Trigger Lock-based formulations of opioids. US FDA has issued a “Draft Guidance for Abuse Deterrent Opioids” on January 9, 2013.
A priori, Trigger Lock™ has the potential to satisfy the FDA Draft Guidance for Abuse Deterrent Opioids:
- Laboratory-based in vitro manipulation and extraction studies (Category 1)
- Success with Trigger Lock™
- Pharmacokinetic studies (Category 2)
- Success with Trigger Lock™
- Clinical abuse potential studies (Category 3)
- To be performed prior marketing
- Analysis of post marketing data to assess the impact of an abuse-deterrent formulation on actual abuse in a community setting (Category 4)
- To be performed post marketing