Publicação
Optimization of 3D porous structures for controlled drug delivery using quality by design method
| Resumo: | The objective of this work was to apply Quality by Design approach to obtain the best conditions to produce 3D polymeric structures for two distinct applications: oral and vaginal route of administration. The first should release 50 mg drug/g scaffold, in 5 hours and the second one 800 mg drug/g scaffold, during 8 h. Initially, the data from previous studies was collected and inserted in MODDE software, and then the Design Space was built and according to those plots, the conditions to start the experimental validation were chosen. The model chosen to perform these studies was Partial Least Square Regression. Both green (probability of failure lower than 5 %) and yellow (probability of failure lower than 10%) zones from Design Space were taken into account and explored. For experimental validation, through the data obtained from QbD studies, scaffolds of chitosan (CHT), xanthan gum (XG) and mixture of CHT and XG were prepared, with N-N’-methylene-bis-acrylamide (MBA) as a crosslinker and tetramethylenediamine (TEMED) and ammonium persulfate (APS) as catalyst and initiator. For the characterization of the produced structures, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy – attenuated total reflectance (FTIR-ATR), mechanical analysis and swelling tests were performed and the ones that achieved the objective regarding morphological and swelling characteristics were chosen for drug impregnation and drug release studies. Additionally, mathematical models were adjusted to the experimental release profiles in order to describe the drug release mechanisms. The studies showed that the porous scaffold that showed better performance for oral route of administration, considering the defined goals, was CHT_6, with 3% chitosan, 2% crosslinker and freezing temperature of -20ºC, that presented drug release of 63,6 mg IBU/g scaffold, in 5 hours. CHT_7, with 3% chitosan, 2% crosslinker and freezing temperature of -80ºC achieved the objective in the second hour, releasing approximately 70 mg IBU/g scaffold. Regarding vaginal route of administration, the scaffold that showed better performance was CHTXG_1 which released 1200 mg IBU/g scaffold, in 8 hours, however, CHT_7 was also very close to the objective, releasing 720,1 mg IBU/g scaffold. Quality by Design approach was an essential and important tool during the development of these structures, once it allowed achieving the objectives set for this thesis, and also reducing the experimental shots (in more and less 60%) needed to achieve the desired goals, what reinforces the power of this tool in processes optimization. |
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| Autores principais: | Rodrigues, Catarina de Oliveira |
| Assunto: | Quality by Design Design space Drug delivery Chitosan Xanthan gum |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | The objective of this work was to apply Quality by Design approach to obtain the best conditions to produce 3D polymeric structures for two distinct applications: oral and vaginal route of administration. The first should release 50 mg drug/g scaffold, in 5 hours and the second one 800 mg drug/g scaffold, during 8 h. Initially, the data from previous studies was collected and inserted in MODDE software, and then the Design Space was built and according to those plots, the conditions to start the experimental validation were chosen. The model chosen to perform these studies was Partial Least Square Regression. Both green (probability of failure lower than 5 %) and yellow (probability of failure lower than 10%) zones from Design Space were taken into account and explored. For experimental validation, through the data obtained from QbD studies, scaffolds of chitosan (CHT), xanthan gum (XG) and mixture of CHT and XG were prepared, with N-N’-methylene-bis-acrylamide (MBA) as a crosslinker and tetramethylenediamine (TEMED) and ammonium persulfate (APS) as catalyst and initiator. For the characterization of the produced structures, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy – attenuated total reflectance (FTIR-ATR), mechanical analysis and swelling tests were performed and the ones that achieved the objective regarding morphological and swelling characteristics were chosen for drug impregnation and drug release studies. Additionally, mathematical models were adjusted to the experimental release profiles in order to describe the drug release mechanisms. The studies showed that the porous scaffold that showed better performance for oral route of administration, considering the defined goals, was CHT_6, with 3% chitosan, 2% crosslinker and freezing temperature of -20ºC, that presented drug release of 63,6 mg IBU/g scaffold, in 5 hours. CHT_7, with 3% chitosan, 2% crosslinker and freezing temperature of -80ºC achieved the objective in the second hour, releasing approximately 70 mg IBU/g scaffold. Regarding vaginal route of administration, the scaffold that showed better performance was CHTXG_1 which released 1200 mg IBU/g scaffold, in 8 hours, however, CHT_7 was also very close to the objective, releasing 720,1 mg IBU/g scaffold. Quality by Design approach was an essential and important tool during the development of these structures, once it allowed achieving the objectives set for this thesis, and also reducing the experimental shots (in more and less 60%) needed to achieve the desired goals, what reinforces the power of this tool in processes optimization. |
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