Formulation answer to drug abuse

A new formulation technology developed by Rohm and Haas has the potential to do away with the problem of prescription drug abuse.

Dr Lyn Hughes, senior scientist, process solutions at Rohm and Haas Research Laboratories, took time out of the busy CPhI meeting last week to tell In-Pharmatechnologist.com about the new technology and other progress the company has made in the applications of ion exchange resins in formulation.

Resins have been around for a long time in formulation, emerging in the 1950s as a means of improving the stability and shelf life of compounds such as vitamin B12, and more recently finding applications in taste-masking, extended-release and as tablet disintegrants.

Rohm and Haas decided recently to change its tack slightly on the development of resins in formulation. For many years it allowed its customers to invent uses for the technology, but latterly has started to push its own projects that have arisen from its own R&D efforts.

One of the fruits of this approach has been the determination that the resin can be used to overcome abuse of prescription opioid analgesics, such as Oxycontin (oxycodone HCl). This product is involved in several hundred deaths in the USA every year among people who abuse the product by crushing it.

Dr Hughes explains that the high that can be achieved using crushed Oxycontin or indeed other opioids is related more to the rate of absorption of the active than the concentration. Rohm and Haas' approach is to use ion exchange resins to capture the active into a matrix. Even after crushing, the compound remains a bound within the matrix, so its rate of absorption is not affected.

The technology, called Reduced Abuse, is not yet in any commercial products but is available for licensing, said Dr Hughes, who said that there are a number of opiate drugs that could benefit from the technology.

One interesting possibility arising from the use of the technology might be the re-scheduling of tightly-regulated drugs such as opioids so that they do not require so much control over their prescription and use. Rohm and Haas would not comment on this suggestion, but independent consultants have suggested that this is unlikely, at least in the short-term.

One area which Rohm and Haas is expecting a lot of business opportunities is in taste-masking. Dr Hughes noted that the decline in R&D productivity at big pharma means that fewer and fewer new drugs are in the pipeline. One of the solutions? To reformulate existing drugs into fast-melt and liquid formulations that can provide a competitive edge over rival drugs.

Resins already have a history of use in this setting; Rohm and Haas technology was used in a liquid formulation of GlaxoSmithKline's antidepressant paroxetine, launched more than four yeas ago. Now the key is to compete with other taste-masking approaches, such as encapsulation and coating.

Compared to the rival approaches, resins have the advantage of being extremely stable (aiding shelf life), prevent leaching of the active and allow predictable delivery.

Forgotten treasure​

However, it is in the area of controlled-release that Rohm and Haas believes the use of ion exchange resins and excipients will come into its own.

Dr Hughes told In-Pharmatechnologist.com that resins can be used to control the rate and site of drug dissolution, and a really useful application is in the enhancing the solubility of poorly-soluble drugs.

Poor solubility is often caused by two factors. Firstly the drug itself may not be very soluble, and secondly the crystal structures it forms may have a great deal of lattice energy and resist ingress of water. Resins can not affect the innate solubility of the compound but, because resinates (the drug/resin complex) are amorphous, the barrier of a hygrophobic crystal structure is removed.

"No one has used this for rapid dissolution,"​ said Dr Hughes, although it was first described in the late 1980s by a professor at Aston University in the UK. Rohm and Haas re-discovered the approach in the last couple of years, and is now developing it commercially even though it is not patentable.

There are some limitations, however. Dr Hughes noted that resins can be used to improve the solubility of any drug that is ionisable, but the big obstacle is the dosage required. If more than 200mg of a compound is used, the chances are that the volume of the resinate required will make it unpractical.

The use of resins is all the more appealing now that Rohm and Haas has shown that in many cases the drug and resin can simply be mixed together during manufacture, eliminating the need to make the resinate. Drug-loading occurs in vivo​ in this case.

In addition, by mixing drug resin combinations with resinates, a range of controlled release profiles can be achieved. For example, one formulation of the non-steroidal anti-inflammatory drug diclofenac made during this approach showed a near-constant release rate during a period of several hours. Resins represent a convenient and low-cost option of achieving this goal, according to the company.