Bora Pharmaceuticals looks at how to synchronise and control API delivery, and why extrusion-spheronization offers pharmaceutical companies a robust technique to manufacture today’s most complex therapeutics.
Strategy
Manufacturing spherical oral solid dose pellets via extrusion-spheronization is not new. What is new is that in the right hands, with the right capabilities, this well-understood process stands ready to help lead the development and manufacturing of both today and tomorrow’s complex oral solid dose drug products.
Extrusion-spheronization is an efficient, flexible and fast process for forming uniform pharmaceutical particles. The shape offers great utility to both drug developers and manufacturers. Offering a low surface area to volume ratio, spheronized active pharmaceutical ingredients (APIs) offer a number of distinct advantages that improve the overall manufacturability of complex dose forms.
Spheres offer superior flow and handling characteristics. Spheronized particles offer an ideal shape for transport throughout most OSD manufacturing steps. Because extruded spheres offer improved hardness and reduced friability, they don’t generate dust—helping eliminate the possibility of contamination in processing—another of the sphere’s desirable attributes.
Spheres offer an optimal shape for manufacturing finished drug products. The shape, for example, offers better packing and reproducibility in beds and columns and easier modelling because calculations are based on flow around symmetrical bodies. Spheres are more mixable as well, especially for incompatible APIs,
Suitable for many OSD forms, spheres help optimise finishing steps in manufacture. Spheres can be loaded and packed uniformly into capsules faster and more reliably. The shape and density of spheres also promotes uniform coating with less material, offering flexibility in manufacturing controlled release characteristics.
Sphere of therapeutic influence
Widely acknowledged as a predictable vehicle for the control, distribution and transportation of therapeutic agents around the body, spheronized pellets make a variety of common and emerging controlled release dose forms possible. This includes fixed-dose combinations (FDCs), combined modified release single-capsule forms and emerging multi-unit particulate system (MUPS) tablet designs. Ultimately sphere-shaped pellets offer a variety of physical attributes that drug developers can leverage to control drug delivery, enhance therapeutic performance and aid the patient-centricity of oral solid dose drug products.
An extremely viable technique for product lifecycle management
Extrusion-spheronization is proving to be an extremely versatile and economic manufacturing technique, viable for most of today’s oral solid dose products development paths, including new molecular entities (NMEs), life-cycle management (LCM) extensions and similar over the counter (OTC) marketing strategies.
It can also support emerging (505(b)(2) development pathways including tailoring compounds for paediatric/geriatric applications or developing FDCs to create a new best-in-class patient-centric product.
Form is function and much more
Patient-centricity is manifesting itself across the life sciences industry in many ways. Tailoring medications to better suit a particular patient population’s special needs or enhance healthcare’s ability to prescribe and administer treatments more efficiently, are all, in principle, patient centric.
But where the movement is being realised most profoundly is in drug engineering, with much of pharma pursuing fundamental improvements to the therapeutic formulation, functionality and form of oral solid dose pharmaceutical products.
Single dose, daily regimen improves patient compliance
Modified release formulations can be effective for drug substances that have a narrow therapeutic index or need better dosage compliance. Most patient groups respond well to taking medications that are swallowed, but if a patient has to take their medications multiple times a day, dose compliance can be challenging.
Modifying release means better control of API dosing in-vivo. By managing uptake and bioavailability precisely, modified release formulations offer pharma a way to deliver their actives with fewer, doses – and better control over time to deliver desired therapeutic effect and reduce negative side effects associated with dose spiking.
A solid way to make complex oral dose products
Development of extrusion-spheronization over the past decade has been accelerated by science’s more comprehensive understanding of the raw materials, active ingredients, processes and controls behind the methodology. In addition, how to manage and manipulate those inputs to increase therapeutic performance or modify API release—without compromising the integrity of the compound or molecule has been vital.
Advanced technologies unlocking extrusion-spheronization’s true potential
Extrusion-spheronization is a mature method but the process and the equipment integral to it have advanced over time. The technology itself has seen steady improvement (along with a host of incumbent tertiary systems) and consequently some manufacturers may be better prepared to manufacture complex oral solid dose drug products with this technique than others.
In the context of pharma manufacturing quality, current GMP thinking in extrusion-spheronization means incorporating quality-by-design (QBD) chemistry, state-of-the-art mixing, extruding and spheronizing equipment and entraining it in continuous flow.
Pharma is relying more and more on its contract manufacturing partners to make increasingly complex drugs. For those seeking more strategic outsourcing relationships, it is now more important than ever to match drug strategy as closely as possible to the expertise and technical capabilities of your manufacturing partners.
It’s well known that more experienced project teams can help accelerate go-to-market schedules and technical/operational mastery is a prerequisite. However, to unlock spheronization’s commercial potential the process requires both experience and the investment operationally to do it well and meet all commercial, financial and regulatory expectations.