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By: Chris Altomare

headshot2Over the past two decades, the increased use of opioids for legitimate medical purposes has been paralleled by a substantial increase in nonmedical use and abuse of opioids. The numbers are alarming and have risen to epidemic proportions. According to the Centers for Disease Control and Prevention, nearly 2 million Americans abused or were dependent on prescription opioids. Overdose deaths involving prescription opioids have quadrupled since 1999, with 165,000 people dying of overdoses related to prescription opioids from 1999 to 2014.

Those looking to abuse opioids manipulate the opioid’s dosage form to extract the active ingredient or defeat the extended-release properties of long-acting opioids. Methods of opioid manipulation include crushing or grinding, dissolving in solvents, and heating or freezing. Once manipulated, the abuser either injects, insufflates (snorts), or smokes the opioid to achieve the desired euphoria.

To address the epidemic rise in prescription drug abuse, pharmaceutical companies have been developing abuse-deterrent opioids that are difficult to physically or chemically manipulate. In 2015 and 2016 the Food and Drug Administration (FDA) released innovator and generic guidances to assist developers of abuse-deterrent opioids. Each guidance provides FDA’s current thinking and evaluation procedure of abuse-deterrent formulation (ADF). FDA specifies the types of studies that should be conducted to demonstrate a formulation’s abuse-deterrent potential and how those studies will be evaluated and what labeling claims may be approved based on the results of those studies.

One might imagine the lengths a drug abuser may go in attempts to defeat new obstacles to highly sought after euphoria. Evaluation of ADFs must go beyond simple manipulation and account for ever-evolving abuser techniques. Several simple and advanced abuse techniques are described on open forms and blogs such as BLUELIGHT and Erowid—these are essentially abusers’ handbooks. Swift flow of information among drug abusers increases the daunting task ADFs have ahead. It is clear that as the formulation science evolves so will abusers’ techniques, thus calling on new and improved ADFs.

Do ADFs actually work, though? We must evaluate and stress these technologies to determine their effectiveness. In vitro lab experiments are designed with scientific rigor while also capturing the tools and processes an abuser uses in the “real-world.”

DRUGSCAN has been at the forefront of designing and conducting manipulation and extraction studies and has worked with many of the leading abuse-deterrent opioid developers in the performance assessment of their product’s abuse-deterrent properties. DRUGSCAN’s CAT.one laboratory-based manipulation and extraction studies produce data that can predict a product’s strengths and weaknesses to physical and chemical manipulations. A comprehensive CAT.one study begins with development of an analytical assay to measure API (active pharmaceutical ingredient) in the presence of the drug product’s formulation. Physical manipulation studies are conducted with up to 10-15 different tools to determine the manipulation method that can produce the finest powders and highest API recovery. Extraction studies follow on manipulated and non-manipulated drug products in a variety of common household solvents (water, alcohols, strong and weak acids, strong and weak bases, bleach, etc.) to determine the best solvent and condition (heat, shaking, pretreatments) to recover the maximum API. Extraction is the leading step to enhance API exposure through oral abuse or further API purification by advanced liquid-liquid extraction or precipitation techniques. Syringe-ability/Inject-ability in vitro tests often stand alone in support of an intravenous label claims as no ethical method to assess this in vivo currently exists. Advanced techniques including smoke-ability, chewing simulation, rectal plugging/suppository simulation are investigated as well.

This year, at the 2016 AAPS Annual Meeting and Exposition, DRUGSCAN presented a method of in vitro simulated smoking experiments and exploratory physical manipulation, syringe-ability and rectal plugging experiments on an abuse-deterrent formulation containing polyethylene oxide.

I feel abuse-deterrent formulations have a critical role in diminishing this public health crisis. Specifically, it will directly impact the new abuser population by disrupting the experimental and social stages of addition. In 2014, there were 467,000 adolescents (12–17 years) using pain relievers without prescription, according to the American Society of Addiction Medicine (ASAM). As we make strides in new ADF technologies and observe positive outcomes in society it is important that this progress be followed up with education, treatment, and prevention so the community does not turn to worse and different avenues in search of euphoria.

Mr. Altomare joined DRUGSCAN in 2012 and currently serves as the Director of Pharmaceutical Services. During his time at DRUGSCAN he has led the development of a laboratory-based manipulation and extraction service offering to satisfy the FDA guidance for evaluating abuse-deterrent formulations.