TY - JOUR
T1 - Evaluation of the impacts of formulation variables and excipients on the Drug release dynamics of a polyamide 6,10-based monolithic matrix using mathematical tools
AU - Adeleke, Oluwatoyin Ayotomilola
AU - Choonara, Yahya E.
AU - Kumar, Pradeep
AU - Du Toit, Lisa C.
AU - Tomar, Lomas K.
AU - Tyagi, Charu
AU - Pillay, Viness
N1 - Funding Information:
This work was funded by the National Research Foundation (NRF) of South Africa.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/12
Y1 - 2013/12
N2 - Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (tx%,MDT x%,f1, f2, k1, k2, and kF). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested.
AB - Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (tx%,MDT x%,f1, f2, k1, k2, and kF). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested.
KW - Excipients
KW - Formulation variables
KW - Mathematical tools
KW - Monolithic matrix
KW - Polyamide 6 10
UR - http://www.scopus.com/inward/record.url?scp=84893649409&partnerID=8YFLogxK
U2 - 10.1208/s12249-013-0021-7
DO - 10.1208/s12249-013-0021-7
M3 - Article
C2 - 23990121
SN - 1530-9932
VL - 14
SP - 1349
EP - 1359
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
IS - 4
ER -