Key trends in formulation development for 2018

Controlled-release technologies will continue to be focal point, whereas techniques to improve solubility are likely to gain popularity.

What are the main trends in formulation development as we head into 2018?

We can expect to see pharmaceutical companies continue to focus on developing controlled-release technologies to produce drug delivery systems that can control the rate of release over an extended period of time. In addition, we will see more complex formulations, such as fixed-dose combinations through the use of variably coated multiparticulates or bi/tri-layered tablets and dual release profiles, in which two or more drugs are formulated into one dosage form; for example, using pellets.

As new chemical entities (NCEs) enter the drug pipeline, poor bioavailability is becoming increasingly common. As such, improving solubility will also be a key focus for companies working with drug compounds in the development phases. Specifically, techniques such as hot melt extrusion, which can enhance the solubility and bioavailability of a poorly soluble API through molecular dispersion in a polymeric carrier, are likely to gain popularity, as well as drug delivery systems that can target specific organs and tissues.

Controlled release has become something of an industry hot topic over the last few years. What are the main drivers behind this?

Controlled-release formulations can offer considerable benefits over other dosage forms; for example, a reduced risk of dose dumping, sustained concentration in the blood plasma and reduced toxicity, meaning a lower chance of side effects. In addition, if controlled-release formulations can be harnessed successfully, patients will need to take fewer doses of their medication, which will likely lead to improved patient compliance and ultimately more effective treatment. Controlled-release technologies, such as multiparticulate dosage forms, are also giving the industry real options for drugs that previously have not been viable candidates as a result of stability issues or compatibility challenges.

What should pharmaceutical companies be looking for when outsourcing controlled-release development projects?

Generally speaking, the most important thing to look for when outsourcing controlled-release development projects is a CDMO with previous experience. The complexities associated with developing these dosage forms, such as establishing desired release profiles, selecting biocompatibility materials with the right profiles and managing the risks of dose dumping, mean that a high level of technical capabilities and expertise are required. More specifically, one of the most viable paths for developing controlled release dosage forms is multi-particulate formulations. Pelletisation can mitigate a lot of the problems associated with taking multiple doses and drugs at the same time and as such is becoming an increasingly popular way of producing smarter dosage forms. With this in mind, companies should be looking for an outsourcing partner with the necessary capabilities and technologies that developing and producing multi-particulate drug products requires.

What are the unique development challenges associated with opiate products?

Opioid products have revolutionised the treatment of pain and are widely used as anaesthesia, cough suppressants, diarrhoea suppressants and to reduce surgical pain, injury or trauma, as well as relieve pain from diseases such as cancer. These controlled substances are, however, also highly addictive due to their analgesic nature and although opiates are hugely effective as a prescribed treatment for pain they are also regularly associated with substance abuse. With this in mind, the biggest challenge that formulation scientists face is finding a way to mitigate the possibility of misuse or abuse of the drugs they develop.

As opiate products continue to revolutionise the treatment of pain for a wide range of conditions it is becoming increasingly important to develop abuse-deterrent opioids and products. What are the latest developments in this area?

To avoid the misuse of prescribed opiates, formulation scientists have adopted a number of physical, chemical and pharmacological approaches during the development of opioid dosage forms to produce abuse-deterrent or abuse-resistant formulations.

Abuse-resistant formulations have physical barriers to reduce the chance of drug tampering, for example, some opioid doses cannot be crushed making it harder for the API to be extracted. Abuse-deterrent measures are intended to prevent release of the active pharmaceutical ingredient. Generally speaking most abuse-deterrent formulations contain an opioid antagonist which remains dormant under normal dosing conditions. If the drug is tampered with, for example, crushed or chewed, the opioid antagonist is released and prevents the euphorigenic effects of the medication. Similarly, some formulations include a noxious agent, intended to be unpleasant for the user, which is released if the formulation is altered.