Despite the recent focus on large-molecule biologic therapies, small molecule drugs still make up the majority of medications on the market and in the development pipeline. For this and many other reasons, the importance of solid dosage forms for drug delivery should not be overlooked
At the heart of developments in drug design and delivery technologies lies the goal of improving patient outcomes and the patient experience, which, in turn, can reduce medical spending, improve health and increase pharmaceutical sales. This goal is achievable if the right molecule form, the ri ght formulation and the right dosage form can all be brought together to create a product that suits the patient’s needs.
A survey conducted by eyeforpharma in 2014 revealed that 86% of pharma executives feel that patient-centricity is key to profitability and the development of personalised or targeted medicines represents a major opportunity for the pharmaceutical sector, especially as their benefits are increasingly recognised by patients and payors.1 But, although the pharma industry is aware of the need for patient-centric drug design, progress still falls short of aspirations.
Catalent’s Applied Drug Delivery Institute has been at the forefront of the drive to make industry’s drugs more patient-centric. One of the fundamental beliefs of the Catalent Institute is that patient-centric design starts with a clear understanding of the factors driving patient outcomes during medicinal chemistry, ensuring that the optimal form of the molecule progresses forward. It is then a matter of identifying and optimising the best formulation approach — along with early dose form selection — always with a view to enhancing patient outcomes.
But research conducted by the Catalent Institute suggests that few formulation scientists receive patient-focused input to influence design choices made during development; often, the information that they receive comes during Phase III, which is too late to affect most drug substance and drug product design decisions.
According to a recent study by Tufts, companies spend an additional $300 million in post-approval studies to test new indications, new formulations and new dosage strengths and regimens.2 By investing more — and earlier — in dose design that incorporates patient and prescriber concerns, some of this cost could be avoided. Catalent has a long legacy of drug development and the application of advanced drug delivery technologies to develop dose forms that support more effective therapies.
A broad portfolio of advanced drug delivery technologies is combined with a data-driven approach to development to ensure that the resulting dose form meets all stakeholder requirements. For example, this may involve using a parallel screening platform to ensure the most suitable bioavailability technology for a molecule’s physiochemical characteristics, customising the dosage form with formulation technologies such as the RP Scherer softgel platform to improve bioavailability and reduce food effects, employing OptiDose CR technology or OptiShell technology for controlled release or Zydis orally disintegrating tablets (ODTs) and FlexDoseSM services for added patient convenience.
Decisions taken during the drug substance and drug product design process can have a major impact on patient outcomes. These include improved adherence to the regimen, reduced side-effects and fewer instances of discontinuation of compliance. Through the Institute, Catalent aims to formalise and extend this research by creating links between industry and academia. A recent example of this is the research collaboration on drug delivery for paediatric patients it has signed with the Rutgers University School of Pharmacy.
Current paediatric drug formulations have been shown to be difficult to administer to children, and this increases the likelihood of a medication error when compared with adult formulations. The partnership will therefore examine and highlight the unmet scientific, clinical and patient needs, and look to develop a suitable paediatric-specific drug formulation toolkit to address them.
The increasing complexity of compounds in the pipeline means that many small molecule drugs are facing the challenge of lower bioavailability. This may often be combined with other technical or clinical formulation challenges, such as complex release profiles, the desire to simplify complex regimens with combination drugs and customised dosage forms for specific patient populations and indications.
There is, of course, no “one-size-fits-all” approach to addressing solubility and bioavailability challenges; and with this in mind, Catalent has created the OptiForm Solution Suite. This predictive formulation platform combines a proven, solid-state chemistry high-throughput analysis platform with each of the key formulation enhancement approaches practiced today. Catalent then draws on its delivery expertise, based on more than 80 years of formulation work, to provide dose-form agnostic recommendations, without the need to do the same work experimentally. The platform has now been extended into other challenging areas, such as the complexities of oral peptide delivery and most recently, complex release profile formulations. The intersection between chemistry and biology is complex, and patients are diverse. Using a formulation platform such as the OptiForm Solution Suite and partnering with an experienced early development provider such as Catalent, will deliver the best results.
A study by MarketWatch estimates that non-compliance costs the pharmaceutical industry approximately $564 billion annually.3 Non-compliance can result from many factors, including dose burden, size and quantity of dosage, or patient acceptance. Dosage forms that are more palatable and easier to swallow, and that also reduce the dosing burden and are more convenient to administer, can lead to better compliance, experiences and outcomes for ageing and paediatric populations. These factors can also support better product differentiation, which, in turn, can lead to improved sales and product lifecycles.
Ageing and paediatric populations often present unique challenges to achieving compliance because of difficulties in swallowing. They may benefit from ODTs, which present an improved method of drug delivery that aids acceptance and compliance, and reduces choking risks. The quick dissolution of the tablets also ensures that the medicine has been taken, which is a benefit to the caregivers of both children and the elderly.
Softgel technology offers similar benefits by improving bioavailability and thereby reducing drug loads, as well as encapsulating medication in an easy-to-swallow dose that avoids problems with a bitter tasting API.
The surge in biologic drugs has brought additional challenges, as large molecules such as these are usually administered via the parenteral route. Delivering to the target activity site while minimising the impact on other non-targeted areas will be increasingly important for biologics and other drugs, as will determining how best to deliver new modalities such as gene and cell therapy.
The Catalent Institute has formed the non-invasive macromolecule delivery consortium (NMDC) to assess the current state of play across NMD science and look at the different potential routes of administration: oral, ophthalmic, respiratory and transdermal delivery. Catalent and industry partners, with contributions from several universities in the US and Europe, have compiled a comprehensive guide to NMD, which has been made freely available to both industry and academia. There is a belief in industry that NMD will be possible, but it is also clear that established traditional delivery technologies will only be of limited utility for NMD and it is going to require more innovation.
That said, there is fascinating work going on at both ends of the innovation range; well established formulation and dose platforms are being adapted to solve new challenges, and novel predictive formulation optimisation platforms are being developed to accelerate and optimise formulation development. For example, by combining softgel technology with its OptiGel Bio and Zydis technologies, Catalent has developed new ways to potentially administer peptides and vaccines, therapies typically delivered by injection. Moving from an injectable dosage form to an ODT presents huge advantages for patient compliance, especially for paediatric populations.
Designing drug products to improve patient outcomes will play a significant role in addressing adherence issues, as will identifying ways to deal with polypharmacy issues, including regimens that are predominantly generic. Formulation technologies such as lipid-based drug delivery, spray drying, hot melt extrusion and fluid bed processing can also improve patient acceptance factors by enabling better taste masking, drug loading and controlled release, while providing greater flexibility in dose form configuration that can address paediatric and geriatric populations.
Much work remains to be done to address these specific needs, but user friendly dosage forms provide clear benefits for paediatric and geriatric populations, leading to improved compliance. As the industry continues to move towards, better dose design that addresses the specific patient population, more effective drugs that economically deliver better healthcare are sure to come.