In vitro evaluation of Erlotinib dissolution from pullulan-based particles and simulation of in vivo release using the software gPROMS

• Grant number: 24/04721-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: July 01, 2024
• End date: October 31, 2024
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Simone de Fátima Medeiros Sampaio
• Grantee: Willian Fragali Machado
• Supervisor: Maria Ines Re
• Host Institution: Escola de Engenharia de Lorena (EEL). Universidade de São Paulo (USP). Lorena , SP, Brazil
• Institution abroad: École Nationale Supérieure Des Mines D'Albi-Carmaux, France
• Associated to the scholarship: 23/11796-2 - Preparation of Erlotinib nanoparticles from the amphiphilic and cationic copolymer PULL-DEAE-g-PZLL for obtaining new pharmaceutical formulation for the treatment of cancer., BP.IC

Abstract

The present project proposal aims to carry out a research internship abroad for a period of four months, associated with the scientific initiation project currently under execution by the interested student. In the project developed at EEL-USP, under the supervision of Prof. Dr. Simone F. M. Sampaio, the student applies a pullulan-based polymer, pullulan-DEAE-g-poly(Z-L-lysine) (PULL-DEAE-g-PZLL), previously synthesized by the research group (FAPESP Process 2019/12940-4), for the production of particles containing Erlotinib (ERL) using the method of nanoprecipitation in dialysis. ERL, currently commercially available in the form of Tarceva® pills, is an anticancer active pharmaceutical ingredient (API) belonging to the class of tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR). The API presents a drawback for oral cancer treatment due to its low solubility at neutral pH, which affects its bioavailability after administration. The encapsulation of the chemotherapeutic agent in polymeric particles is proposed as an alternative to improve its physico-chemical and pharmacokinetic properties. Since the pullulan-based copolymer has the ability to self-aggregate in aqueous media forming biodegradable particles, it is an interesting candidate to study the encapsulation and controlled release of ERL, thus modifying its solubility, dissolution profile, and efficacy, as well as potentially reducing side effects caused by chemotherapy. These particles can be administered in alternative routes and different formulation forms, such as parentally or orally, and since ERL encapsulation in pullulan-based particles is still poorly studied, the evaluation of the drug's release profile and bioabsorption from these formulations needs to be further explored. In this context, the objectives of this proposal for an internship abroad are to evaluate the in vitro dissolution profile of ERL from the solid formulations in media that simulate the gastrointestinal absorption as well as to apply the data obtained to simulate the in vivo absorption of the drug, using gPROMS® as a software. The project was encouraged by the contact of the student and his advisor with Prof. Dr. Maria Inês Ré and Prof. Fabienne Espitalier, professors at the Centre RAPSODEE of IMT Mines Albi. Prof. Maria Inês is also the director of a technology platform on advanced pharmaceutical formulations to support the industry (GALA platform). Since Centre RAPSODEE has the software license and trained personnel to develop in vivo release simulations, and both professors have already demonstrated their interest in mentoring a student to work with ERL simulation, Centre RAPSODEE became a great opportunity for the student to be able to deepen their knowledge in their scientific initiation project and learn more about mathematical simulation in the context of pharmaceutical formulations. The host institution, IMT Mines Albi, France, is a well-established school, especially when it comes to establishing cooperation between industry and excellent universities in and outside of France, providing great opportunities for research development in the research field of interest of this project. It is important to emphasize that Dr. Maria Inês and Dr. Fabienne Espitalier have extensive experience in the field of pharmaceutical technology applied to processes for generating polymeric particles. This BEPE grant, if approved, will greatly add to the project already developed by the student in Brazil, since it will provide the student access to the software license and trained personnel, currently not available in Brazil. Furthermore, it will be an opportunity for improvement in the knowledge about drug release evaluation and behavior in solid oral administration of Erlotinib. Finally, the research internship will have a very significant contribution to the student's professional and personal life.