RAMAN MICROSCOPY VALIDATION OF A COMPUTATIONAL MODEL OF DRUG RELEASE FROM A HYDROPHOBIC MATRIX

CORTEZ TORNELLO, PABLO R.; CISILINO, ADRIÁN; SEOANE, IRENE TERESITA; ABRAHAM, GUSTAVO A.; TOMBA, PABLO

Santa Fe

Congreso; ENIEF 2019 - XXIV Congreso sobre Métodos Numéricos y sus Aplicaciones; 2019

CIMEC y Asociación Argentina de Mecánica Computacional

Controlled drug delivery systems are efficient, versatile and safe means for the pharmacological treatment of human diseases. Controlled drug delivery technology facilitates the transport of a pharmaceutical agent to a specific area of the body and assures the release of the agent into a therapeutic level for a sustained period of time. This work contemplates the modeling of the release of a drug, embelin, from polycaprolactone (PCL) matrices, using a one-dimensional finite difference method. Embelin is a therapeutic agent of natural origin, poorly soluble in water and presents various biological properties, including antimicrobial, antifungal and analgesic applications. PCL is a bioresorbable and biocompatible polyester. It was observed that PCL scaffolds containing embelin present attractive release profiles to be used as controlled delivery systems (Cortez Tornello, P.R., Feresin, G.E., Tapia, A., Cuadrado, T.R., and Abraham, G.A., Multilayered electrospun nanofibrous scaffolds for tailored controlled release of embelin. Soft Materials, 16: 51?61, 2018). Swelling and erosion of the matrix into the release time were disregarded from the modelling due to the hydrophobicity and the high resistance to hydrolysis of PCL. This work introduces a release model for the embelin-PCL system that assumes a dual initial dispersion of the embelin: agglomerated and well dispersed. The model accounts for the combined effects of simultaneous diffusion of the embelin and water, and dissolution of the solid fraction of embelin within the wetted matrix. The model formulation and validation are based on the results of embelin release experiments and Raman microscopy observations. The Raman microscopy observations provide the information to characterize in-depth embelin spatial distribution, which was found as a key factor for the model development. The model obtained allowed to adjust the release behavior and identify the involved mechanisms, finding that the controlling mechanism is the drug dissolution of both dispersed forms.