title: 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.
abstract: 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 (t x%, MDT x%, f 1, f 2, k 1, k 2, and К F). 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.
authors.affiliation: Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
authors.forename: Oluwatoyin A
authors.initials: OA
authors.lastname: Adeleke
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Lomas K
authors.initials: LK
authors.lastname: Tomar
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000737:chemistry; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data*; D004573:Electrolytes / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D015233:Models, Statistical; D009757:Nylons / Q000737:chemistry*; D010316:Particle Size; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004573:Electrolytes; D005079:Excipients; D009757:Nylons; D010726:Phosphodiesterase Inhibitors; C045688:nylon 6-10; D000639:Amitriptyline; D013806:Theophylline