Conventional drug delivery methods, such as oral and systemic administration, face issues of optimisation, and present certain challenges for physicians. Proventa spoke to Professor Afzal Ur-Rahman Mohammed, Head of Pharmaceutical Sciences at Aston University Pharmacy School, about these challenges, and how conventional systems compare with alternative methods like viral vectors.

In your clinical experience of drug development, how do you begin to choose a drug delivery system? What factors have to been taken into account for specific diseases?

There are three specialisms involved here. One is the drug discovery group – their focus is identifying appropriate targets and identifying drug candidates suitable for that category/target. On the other extreme is the recipient group, i.e. working with patients who will be using the drug. The formulation group sits right in the middle. This is a very interesting challenge, and in some cases a dilemma. You’ve got to tailor the formulation so that you meet the challenges presented by the drug candidate itself, but you’ve also got to develop a formulation acceptable for your target population.

Typically the majority of the drugs discovered are purely water insoluble, which have issues with bioavailability. Therefore, if you decide to instead directly inject them into the bloodstream, there is a significant amount of formulation work that must be done. Within that, you’ve got to be mindful of where that formulation is to be used, what the conditions are, and patient requirements. This is we what we need to take into account when deciding on a suitable delivery system. It’s that sort of process where the formulation group tries to bridge the challenges presented by the drug with the challenges or the requirements of the target patient population.

Now when you’re overcoming these bioavailability challenges, there are a number of different strategies that can be applied to overcome poor solubility. You’ve got to be mindful of a suitable delivery system that can actually overcome the challenges. For example, in situations where you’ve got the option of formulating tablets that disintegrate in the mouth, you’ve got to be aware of the drug properties around taste, solubility, and the absorption profile, and then tailor that to see if that would be an appropriate delivery system for the target population.

It’s not so much about the target as about the target site. It’s the barriers you need to overcome, and at the same time the challenges presented by the drug molecule itself. It’s finding an optimal solution that addresses both.

Your most recent paper highlighted some of the challenges with oral administration. Could you go into further detail about some of the issues that arise in clinical research with this method (e.g. patient adherence)?

Now that’s an interesting article in my opinion, because a vast majority of formulations in the market are swallowable tablets. One of the biggest challenges with tablets, especially in the elderly population, is ease of swallowing. What we have done in the past few years is look at how we can overcome this challenge, without manipulating the existing tablet dosage form, by adding an additional layer on top.

We looked at various coating compositions, which would enable swallowability without compromising the typical tablet properties. Dosage tablets have to have a certain release profile, must disintegrate in a given time, and be mechanically strong. So without compromising the core tablet properties, just by introducing an additional layer of film coating we are able to improve the swallowability of these solid dosage forms. That was one key outcome of that paper.

Another interesting outcome was that we’ve actually developed a quantifiable swallowability metric called a ‘swallowability index’ which gives you a snapshot of these systems and how well these film coatings ease or help with swallowability. If you can quantify something, it becomes easier when you are assessing its suitability in patients. You can see if patients find the tablets easier to swallow, or perhaps identify which tablets are harder to swallow.

Bioavailability is obviously a big factor in drug delivery. How well do you think conventional methods like oral/systemic administration compare with alternative methods like viral vectors?

Viral vectors are generally used for biological compounds. These delivery systems are predominately used in vaccine formulations, not so much in other biological drugs or gene therapy. Equally, you can see for instance the difference types of COVID -19 vaccines that have been approved. There is an emergence of nano-particle lipid-based formulation, like the formulation prepared by Pfizer or Moderna. They are not based on viral vectors, but are synthetic delivery systems made from lipids. The vaccine made by the Oxford/AstraZeneca operation is based on a viral vector system. So viral vector systems can deliver biologicals, but when it comes to small molecule drugs, the preference would be to go with conventional delivery systems such as tablets, capsules, inhalers, creams etc.

How do you believe oral drugs compare in efficacy and tolerability with short-term invasive techniques in delivering agents directly into the brain?

Each of these methods has its own advantages revealed on a case-by-case basis. For long-term therapy, clearly invasive techniques are very expensive, patient compliance could be potentially compromised, and it depends on the condition as well. In cases where the patient is having to travel long distances or has issues with mobility, but you’re expecting them to have frequent clinic visits on a long-term basis, then patient compliance is likely to be compromised. Equally however, that could be the only way to treat that condition. The preferred drug delivery system is conventional, including drugs delivered through intravenous infusions. Only recently have there been some breakthroughs around oral delivery of these biological compounds, due the stability of these in the gastrointestinal tract and the absorption profile resulting in poor bioavailability. To some extent, it is being addressed with new technologies in the market, looking at delivering these difficult drugs through the oral route.

In terms of neurological disorders, we’re talking about solubility, permeability of the drug, and sensitivity to pH. It’s not an easy thing to do. However, if some of the challenges can be addressed at the start of the process, then potentially this could give more freedom for the formulation scientists in terms of the type of delivery systems that can be formulated. As I mentioned, you’ve got three key areas here. The discovery, the formulation and the patient group. If you can reduce the challenges presented by the drug discovery group, then the formulation group can focus and tailor the formulation to better meet the target patients.

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Charlotte Di Salvo, Junior Medical Writer
Proventa International