Aline Moulin, , Pharma Insights Contributor,  Pharmaceutical Development Director, Skyepharma

Oral solids continue to be the most commonly used delivery vehicle to get drugs to patients for three main reasons: they are cost effective, relatively easy to manufacture, and most importantly, are patient friendly.

By the numbers, oral solid dosage (OSD) products remain the largest segment of the pharmaceutical market. The global OSD pharmaceutical formulation market is forecasted to grow from $493 billion in 2017 to $926 billion by the end of 2027, according to Future Market Insights. This represents a compound annual growth rate (CAGR) of 6.5% over the 10-year forecast period.

This trend has been towards specialist CDMOs, as they often offer better continuity from development through to commercial requirements. Depth of specific expertise in applicable technologies is also imperative, as it can often accelerate timelines and provide higher quality outcomes. This is critical in a market in which “getting it right” quickly is typically far more valuable to sponsors than saving money on a per-line-item basis.

The current state of the OSD market is both mature—in that conventional tablet formulations and capacity exist—and immature—in that new formulation capabilities need to be developed and improved for more complex problem statements like bioavailability enhancing technologies and patient-centric dosage forms like controlled release products.


For several decades, the drug discovery process has been influenced by automation technologies, such as high-throughput screening, combinatorial chemistry, and computer-aided drug design. The drug candidates that emerge from these screening programs are highly efficacy due to their good fit with the target-receptor geometry. Unfortunately, many of these highly active drugs are poorly soluble. The majority of drugs in the development pipelines of pharma companies have solubility and related oral bioavailability problems. Poor solubility of drugs is oftentimes associated with poor bioavailability, in particular, after oral administration.
But long before one of these compounds can reach the market, however, it needs to be formulated for preclinical studies and for the pharmacological activity tests. Therefore, it is a great challenge for the pharmaceutical development to create new drug delivery systems and formulation approaches to overcome the solubility and bioavailability problems of these drug candidates.

This challenge can be addressed with IDD® DISSOCUBES™ technology, using the Microfluidizer® process, as previously described. This technology allows particle size reduction, which is a universal approach to improve the bioavailability of poorly soluble drugs. The decreased particle size of drug nanocrystals leads to a distinct increase in surface area. Due to the increased surface area, the rate of dissolution will be proportionally raised, leading to a better absorption of the poorly soluble drug. Thanks to this technology, Skyepharma developed the fenofibrate drug product (1), now commercialized on the US market as Triglide™ (

).

Skyepharma is so able to develop and commercially manufacture oral dosage forms with improved bioavailability thanks to its Microfluidizer® technology expertise in API particle size reduction.


Indeed, another key trend affecting the global OSD market is the rise of useability and patient compliance as a key concern for drug developers. This increasingly patient-centric approach is fueling a rapid rise in demand for modified-release (MR) OSD products.

Developers are turning to MR technology to meet their useability goals for a number of reasons. First, it can be used to extend the period of time that a medicine remains active in the body by maintaining therapeutic blood concentrations for longer than traditional immediate release products. Second, it can delay action until a drug has reached a specific area, such as the small intestine, through the use of special coatings. Lastly, it can also be harnessed to create fixed dose combinations, multi-API products, with the doses of each API designed to be released at different rates.

These features offer huge benefits for patients. They can enhance the therapeutic effect of a drug and can potentially reduce adverse side effects by delaying activity until it reaches the target area and lowering plasma peak concentration while maintaining the desired therapeutic effect. Most importantly, they can reduce the number of daily doses required, making them more user friendly and enhancing patient compliance. These patient-centric benefits can help OSD products maintain market share when compared with rival dosage forms.

To answer each of these challenges, Skyepharma has a number of technologies to propose to its clients. Among those proprietary technologies, two have already been on the market for more than 25 years, are well recognized from the scientific community, and the drugs based on them have demonstrated strong efficiency and efficacy over the years: Geomatrix® Technology and the Geoclock® Technology.


Geomatrix® Technology and Geoclock® Technology allow us to answer a number of difficulties regarding the complex release profiles expected for the drugs. Using these technologies, we can propose and design standard immediate-release profile drugs or formulations; we can also provide delayed-release profiles and sustained-release profiles, which are both part of the broad and multiple family of MR formulations. These particular drug profiles can be proposed as individual release systems. However, they can also be proposed as a combination of two or more release profiles for one or more APIs to achieve, for instance, a so-called multipulse (or chronotherapeutic) release profile’s drug product, or a combination of immediate-release and delayed-release drug product. Another combination possibility involves an immediate plus a sustained release formulation, also known as the quick-slow release pattern.

The very precise finetuning of the release profiles is key today to answer the specific target product profile (TPP) that are desired by the pharmaceutical companies. This can be achieved by using different technology approaches and at Skyepharma, we can propose to our clients either off-the-shelf technologies or our own proprietary technologies.


Articles

Focus on the contribution of modified release technologies