The new formulation in modified-release tablets seeks to reduce adverse effects such as drowsiness and optimize dosing, especially in fertility treatments. Promoted within the framework of the Industrial Doctorates Plan, the project combines the experience of the pharmaceutical company SEID SA and the knowledge of the Drug Development Service of the University of Barcelona.
The research team of the Catalan pharmaceutical company SEID SA and the University of Barcelona, led by industrial doctoral student Ana Isabel Gavilan Martin, is developing a new formulation of natural progesterone in modified-release oral tablets. The project, which is currently in the pre-formulation phase, aims to create a more effective, safe and comfortable medicine for patients who require hormonal treatments in areas such as gynecology, obstetrics and, notably, assisted reproduction. This innovation seeks to overcome the historical challenges of oral progesterone, such as low absorption and side effects, while optimizing industrial production costs.
From the point of view of women's health, natural progesterone is a fundamental hormone, essential in the regulation of the menstrual cycle, the maintenance of pregnancy and in supportive therapies during menopause or in fertility treatments. Despite its importance, its administration has always posed a challenge for pharmaceutical technology. " Its poor oral bioavailability constitutes a significant limitation, which makes the development of effective oral pharmaceutical forms a relevant technological challenge" , points out Gavilan, the industrial doctoral student of the project.
For years, the parenteral route (injectable) was the only viable option to ensure its effectiveness, an invasive and uncomfortable solution for patients. The situation improved in the 1980s with the arrival of micronized progesterone (a process to reduce the size of the drug's particles to facilitate absorption), formulated in oily soft capsules. This was a notable advance, but not the definitive solution, Gavilan also comments.
Regarding the current treatment, it still presents significant drawbacks, since the manufacturing process of the soft capsules is expensive and complex. Furthermore, in treatments such as assisted reproduction, the doses are usually very high to compensate for the low absorption, which causes adverse effects such as drowsiness, dizziness or lightheadedness, which directly affect the quality of life of the patients.
The innovation: modified-release tablets
Faced with this scenario, the industrial doctoral project between SEID SA and the University of Barcelona proposes an innovative solution: developing modified-release tablets. Unlike a conventional tablet that releases the active ingredient all at once, this technology allows progesterone to be released gradually and in a controlled manner in the body.
Therefore, the main objective of this strategic research is to “ improve the pharmacokinetic profile of the active ingredient by offering a more effective oral medication, with fewer adverse effects and more comfortable for patients ,” says the project team. In other words, the aim is for a greater amount of medication to reach the blood constantly and for a longer period of time, avoiding the concentration peaks that often cause side effects.
Gavilan specifies that one of the key hypotheses is that a prolonged release formulation could favor the absorption of progesterone through the lymphatic route. This alternative mechanism would reduce the so-called “ hepatic first pass effect ”, a process in which the liver metabolizes and eliminates a large part of the drug before it can act, forcing the administration of higher doses. If achieved, a greater amount of intact progesterone would reach the systemic circulation, improving its effectiveness.
The challenge of formulation
The doctoral student acknowledges that the path to creating this new medicine is complex and requires great scientific precision. That is why one of the main technical challenges is the very nature of the active ingredient: “ progesterone is an active ingredient characterized by its low aqueous solubility, which limits absorption and can compromise its bioavailability ,” explains Gavilan.
This is where the preformulation studies come into play, a crucial phase of the project. These studies are the foundation on which the entire drug will be built. According to the team, “ their aim is to characterize the physicochemical properties of the active ingredient, as well as analyze its stability against critical factors such as oxidation, temperature, humidity and light .” In addition, at this stage, the compatibility of progesterone with excipients, which are the inactive components of the tablet (such as binders or coatings), is analyzed. The choice of these excipients is vital, since “ they have the function of facilitating the administration of the drug, protecting the active ingredient from degradation and ensuring an adequate release that optimizes its bioavailability .”
At the same time, during the research, exhaustive stability studies are carried out, tests that allow " to obtain scientific evidence on the evolution of the quality of the medicine over time, which is essential for establishing its shelf life and defining the optimal storage conditions ". In short, only by guaranteeing that the medicine maintains its properties intact can its efficacy and safety in the long term be ensured.
"The main objective of this strategic research is to improve the pharmacokinetic profile of the active ingredient, offering a more effective oral medication, with fewer adverse effects and more comfortable for patients."
A strategic alliance between industry and academia
The success of a project like this does not only depend on science, but also on collaboration. This industrial doctorate brings together two key players in the Catalan ecosystem. On the one hand, from the socio-economic sector, Laboratorios SEID participates, a pharmaceutical company with more than 65 years of experience and specialized in women's health. Based in Lliçà de Vall (Barcelona), SEID contributes its industrial vision, its knowledge of the market and its ability to take a product from the laboratory to pharmacies.
On the other hand, on the academic side, the Drug Development Service (SDM) of the Faculty of Pharmacy of the University of Barcelona collaborates, a reference center in technology transfer. Founded and directed by Dr. Josep Maria Suñé Negre, the SDM has more than 25 years of experience and has participated in more than 300 industrial projects that have resulted in more than 100 commercialized products. This trajectory provides scientific rigor and experience in galenic development that are indispensable for a project of these characteristics.
This collaboration enables the journey of the new medicine, which begins at the SDM facilities, where a robust formulation is developed. Subsequently, the academic knowledge is transferred to SEID, which is responsible for the preclinical studies and, finally, the clinical phases with patients. Once the safety and efficacy have been validated, SEID will be the one who will submit all the documentation to the Spanish Agency for Medicines and Health Products (AEMPS) to obtain marketing authorization.
The project is currently in the pre-formulation and stability studies stage. Although the road is long, if the results are positive, the team estimates that the new formulation could be ready for the first clinical trials within 12 to 24 months. Consequently, the potential benefits for patients are multiple and significant. Firstly, the reduction of adverse effects such as drowsiness or dizziness. Secondly, the possibility of optimizing doses, which in some treatments can be very high. This improvement would not only increase the comfort and quality of life of patients, but would also promote better adherence to the treatment, a key factor for its effectiveness.
In the context of assisted reproduction, the impact could be even more profound. As the team explains, “ the development of more effective and safer hormonal therapies represents a fundamental advance .” Therefore, a formulation that allows for precise dosing and efficient absorption “ favors embryonic implantation, increases cycle success rates, and reduces the need for repeat treatments .” These advances, Gavilan concludes, reduce the physical and emotional stress that women suffer in these processes.
"Being part of a project that can transform the field of women's health represents a deep commitment to an often invisible but essential cause."
A commitment to women's health
Beyond pharmacological innovation, projects like this have a profound social and professional significance. The industrial doctoral student is clear in this regard: “ being part of a project that can transform the field of women's health represents a deep commitment to a cause that is often invisible, but essential ”. For decades, many health problems that specifically affect women have been underrepresented in research, and initiatives like this help to correct this imbalance. This task, continues Gavilan, “ means being an active part of a necessary change towards a more inclusive, humane medicine that is aware of the specific needs of women throughout all stages of their lives ”.
Developing a new drug is a journey full of challenges. For this reason, the team advises new industrial PhD students who want to embark on a similar journey to base their projects “ on solid scientific and strategic foundations .” They also recommend seeking the support of experienced institutions, choosing a good mentor, and ensuring technical, regulatory, and economic viability. Finally, they emphasize the importance of working on a line of research that generates interest, not only scientifically, but also “ for its potential social and commercial impact ,” since this is what ultimately allows a laboratory idea to become a real solution for people.
