The Demands of the Perfect Dose

The Demands of the Perfect Dose

The Demands of the Perfect Dose
As the development pipeline becomes more saturated with complex molecules and patient experience becomes more important, developers are looking to outsourcing partners to provide more specialized expertise and solutions. Oral-solid dosage forms remain the most common drug formulation used within the pharmaceutical industry and, according to market research, should continue to experience market growth in the near future. However, a range of factors, such as an amassing focus on biologics, higher proportion of poorly soluble molecules in the development pipeline, and regulatory development pathways, are potentially set to shift the balance and raise the profile of newer, innovative dosage forms, increasing the requirement for expert skills.

Overcoming bioavailability issues

A major challenge currently impacting drug development is overcoming bioavailability issues, which is becoming more difficult as a result of the increasing number of complex and poorly soluble molecules entering the development pipeline.

“The ‘put it in a tablet’ dosage form approach that may have worked in the past is no longer effective as molecules require more complex and advanced drug delivery technologies that address insoluble compounds,” explains Robert Lee, President of the CDMO Division of Lubrizol Life Science Health. “There are a range of technologies to increase bioavailability but for them to be viable, expertise and experience on how to apply them are required so formulations stand a better chance of being effective.”

Adoption of an orthogonal approach and being open to a variety of methods, particularly during early development, was also advised by Dr. Lee. “Good development practice starts with the client providing a clear target product profile (TPP), which describes an idealized drug product image, including route of administration, dose, form factor, pH, particle size distribution, and so on,” he continues. “Once there is an understanding of the TPP and the physicochemical characteristics of the active, it is possible to assemble potential drug delivery technologies that may achieve the TPP.”

Advantages of the accelerated pathway

Speeding up the development pathway has obvious benefits for drug developers. Not only can these accelerated routes help shorten the development timeline, but they can also offer significant cost reductions.

Using the US FDA’s 505(b)(2) pathway as an example, Dr. Lee highlights that innovative drug dosage forms are being realized thanks to the opportunities afforded by the accelerated development route. “A key advantage of the pathway is the 505(b)(2) sponsor can use clinical data produced by other companies to seek FDA approval without performing all the work required with a traditional new drug application,” he says. “This pathway is being used to improve existing drug products with new dosage forms, indications, dosing regimens, and new routes of administration.”

On a global scale, other regulatory bodies also offer accelerated route options. For example, in Europe, the European Medicines Agency (EMA) allows developers to submit applications via the hybrid procedure, which is considered to be roughly equivalent to 505(b)(2). “The appeal of accelerated pathways is leading drug innovators to rethink existing market medicines and reformulate them in ways that place a greater emphasis on patient-centricity,” confirms Dr. Lee. “This is leading to innovations such as long-acting injectables that require a lower dosing regimen than before or improving the bioavailability of a drug so that it can be delivered via an alternative, more convenient route of administration.”

Focusing on the patient

A patient-centric approach to dosage form can be particularly vital when considering specific patient populations. “Traditional dosage forms, particularly tablets, may not always be taken by a patient as prescribed, which can lead to a negative therapeutic outcome and render a course of treatment much less effective,” says Dr. Lee. “Pediatric and geriatric patient populations are particularly averse to swallowing large tablets, and in these cases, powders or liquid formulations can provide a much more convenient method of administering a therapeutic.”

Gaining unique access through outsourcing

Dr. Lee says that working with an outsourcing partner for formulation and development can be particularly relevant for non-conventional dose forms. “Dosage forms, such as nasal and ophthalmic, as well as implantable devices and depots, can have additional complexity and regulatory issues for developers to consider,” he notes. “Through an outsourcing partner, developers can access expertise and technologies that they do not possess in-house.”

A further benefit for Dr. Lee is that an outsourcing partner can also provide an extension to a developer’s available resources. “If there is a backlog or lack of available resources with the client, they can use an outsourcing partner as an extension of their internal development teams,” he says.

Areas of growth

In Dr. Lee’s opinion, routes of drug administration that have been previously overlooked, such as nasal dosage forms, will experience growth in the near future. “Nasal delivery can offer an ideal route and increased bioavailability for several drug types, particularly those indicated to treat the central nervous system,” he explains. “This route of administration may also be suitable for non-conventional APIs, such as biologics.”

Ultimately, however, keeping the patient in mind when looking at drug development is and will remain to be of critical importance, emphasizes Dr. Lee. “If a patient does not like the dosage form then they are unlikely to take the drug, leading to negative therapeutic outcomes,” he concludes. “Dosage forms should appeal to, not repel, the target audience.”

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