Gemma Budd, healthcare business manager, Lucideon, explains how the company’s development of a ceramic pill is helping tackle prescription drug abuse
Prescription drug abuse is a global epidemic; in the USA, more people die from this than from abusing illegal drugs such as heroin. As such, the FDA is leading a drive to make addictive drugs ‘abuse-deterrent’, starting with the opioid family of substances e.g., oxycodone and morphine; a guidance document was released to this effect last year.
Typical abuse mechanisms often revolve around crushing the pills down until they become powders. This provides easier access to the drug and sometimes even direct access depending on the formulation design. Abusers may then try to extract the drug from the powder (and even the pill in its uncrushed form) by trying to dissolve the powder/pill in solvents such as alcohol, vinegar or orange juice. Melting the powder is another method that an abuser may use, to render it in a liquid state that can then be injected. All of these methods, including snorting of the powder, are used by the abuser to get the addictive euphoric ‘high’ as quickly and effectively as they can. Not only is this dangerous for the patient’s health, but society too suffers from the crime and unemployment that drug abuse fuels. Drug abuse is a huge cost burden on national governments and one that is increasing.
Technologies to combat this abuse are in development. Typically, these use polymer excipients and/or a complicated tablet design. The resulting tablets are often big and hard and therefore difficult to swallow. While this makes them more difficult to abuse, it also makes them more difficult for the non-abuser to take – this is a challenge for many abuse deterrent formulations.
Abuse deterrent technologies are often also an ‘add-on’ to a formulation, ie, they have a controlled release technology and a separate abuse deterrent technology. This adds time and cost both to the development of the drug and to its manufacture.
Lucideon has revitalised an age-old inorganic synthesis process to control the microstructure of these inorganic materials such that they are highly porous – with pore sizes of less than 10nm and an extremely high surface area. The drug compound is encapsulated into these pores using proprietary processing techniques, and how quickly the drug is released over time is controlled by this resulting porosity.
Importantly, the iCRT particles act as both the controlled release technology and provide the abuse deterrence properties – this is beneficial for pharma companies and for patients as the formulation is streamlined. The ability to offer both controlled release and abuse deterrence properties is partly due to the natural benefits of inorganic materials. Lucideon optimises these benefits through some clever materials science and processing to give the key features, including:
- They don’t melt until you reach in excess of 1000 degrees Celsius (meaning any attempt to heat the carrier to expose the drug will just result in destruction of the drug – see below)
Pre-melting the tablet contains the drug
Post melting the drug is destroyed but not the carrier
- They don’t dissolve easily (meaning any intent to inject the product would mean injecting hard particles into the veins – which is nigh on impossible anyway)
- Crushing these materials is very difficult – reducing the particle size of these materials in a reasonable time period requires industrial equipment.
Furthermore, it is virtually impossible to crush these particles down to less than 10nm (whereby the pores become non-existent and the drug becomes readily exposed) even with industrial equipment, so even with finely crushed powders the formulation still retains significant control over the drug release. In fact, Lucideon purposely formulates the iCRT material as a powder – this makes it easy for its pharmaceutical partners to process the materials as usual into a final dosage form eg, tablet.
Through extensive internal R&D and years of experience of these materials in industry, Lucideon has identified a ‘sweet spot’ in the process design space that delivers powders that give the desired drug release rate, yet result in a microstructure and surface functionality that does not encourage or allow for forced extraction when exposed to organic solvents like alcohol. There is a very complex interaction between the variables of the synthetic process, as well as between the drug compound and the surface of the pores, and if you venture outside a certain range of processing variables, the resistance to solvent extraction disappears along with half of the benefits. It is Lucideon’s expertise in controlling these materials that accelerates the optimisation of the technology, such that the technology can be tailored and exploited quickly for multiple different drugs.
Lucideon is already working with pharmaceutical companies to commercialise this technology for some opioids and, with the growing rate of drug abuse, and there is no doubt that the technology will be used in many different product formulations over the next few years – initially across the opioid space but also in drugs for treating ADHD, depression and schizophrenia – all of which have high abuse potential and are no doubt next on the list for FDA and other regulatory bodies.