A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages
European Journal Of Pharmaceutical Sciences
| dc.creator | Catalan-Figueroa, Johanna | |
| dc.creator | Boisset, Constanza B. | |
| dc.creator | Jara, Miguel O. | |
| dc.creator | Flores, Mario E. | |
| dc.creator | Moreno-Villoslada, Ignacio | |
| dc.creator | Fiedler, Jenny L. | |
| dc.creator | Morales, Javier O. | |
| dc.date | 2020-02-13T12:48:36Z | |
| dc.date | 2022-07-07T23:41:36Z | |
| dc.date | 2020-02-13T12:48:36Z | |
| dc.date | 2022-07-07T23:41:36Z | |
| dc.date | 2018 | |
| dc.date.accessioned | 2023-08-22T22:40:28Z | |
| dc.date.available | 2023-08-22T22:40:28Z | |
| dc.identifier | 21120192 | |
| dc.identifier | 21120192 | |
| dc.identifier | https://hdl.handle.net/10533/237762 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8347939 | |
| dc.description | Oral bioavailability of loperamide is restricted by its limited absorption in the gastrointestinal tract due to its poor aqueous solubility and its P-glycoprotein (Pgp) substrate characteristic. In addition, ammonium methacrylate copolymers have shown to have mucoadhesive properties, whereas poloxamer 188, has been suggested as a Pgp inhibitor. Thus, in this work, we evaluate conditions that affect physicochemical parameters of ammonium methacrylate/poloxamer 188-based nanocarriers loaded with loperamide hydrochloride. Nanocarriers were synthesized by nanoprecipitation, enhancing loperamide encapsulation efficiency by modifying the aqueous phase to basic pH. The isolation of the non-encapsulated drug fraction from the nanocarriers-incorporated fraction was conducted by centrifugation, ultrafiltration, vacuum filtration and diafiltration. The last method was effective in providing a deeper understanding of drug-nanocarrier loading and interactions by means of modeling the data obtained by it. Through diafiltration, it was determined an encapsulation efficiency of about 93%, from which a 38% ±6 was shown to be reversibly (thermodynamic interaction) and a 62% ±6 irreversibly (kinetic interaction) bound. Finally, release profiles were assessed through empirical and semi-empirical modeling, showing a biphasic release behavior (burst effect 11.34% and total release at 6 h = 33% ±1). Thus, encapsulation efficiency and release profile were shown to have a strong mathematical modeling-based correlation, providing the mechanistic approach presented in this article a solid support for future translational investigations. | |
| dc.format | application/pdf | |
| dc.relation | instname: Conicyt | |
| dc.relation | reponame: Repositorio Digital RI2.0 | |
| dc.relation | info:eu-repo/grantAgreement//21120192 | |
| dc.relation | info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477 | |
| dc.relation | https://www.sciencedirect.com/science/article/pii/S0928098718304494?via%3Dihub | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights | CC0 1.0 Universal | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights | http://creativecommons.org/publicdomain/zero/1.0/ | |
| dc.title | A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages | |
| dc.title | European Journal Of Pharmaceutical Sciences | |
| dc.type | Articulo | |
| dc.type | info:eu-repo/semantics/article | |
| dc.type | info:eu-repo/semantics/publishedVersion |