Novel Polyamide 6,10 Variants Synthesized by Modified Interfacial Polymerization for Application as a Rate-Modulated Monolithic Drug Delivery System

Abstract

The aim of this study was to explore and elucidate the possibility of employing an aliphatic polyamide 6,10 (PA 6,10) synthesized by a modified interfacial polymerization process as a novel rate-modulated monolithic matrix drug delivery system. A Plackett—Burman experimental design was used to synthesize 14 different PA 6,10 polymers using the interfacial polymerization process of synthesis comprising the monomers namely hexamethylenediamine and sebacoyl chloride and the solvents namely hexane (nonpolar phase) and deionized water (polar phase). This process was modified by variations in stoichiometry of monomers, volume ratios of solvents as well as solvent phase modification using cyclohexane and sodium hydroxide for the nonpolar and polar solvent phases, respectively. The micromechanical parameters of the newly synthesized PA 6,10 variants were elucidated in terms of the matrix resilience (MR), matrix hardness and deformation energy, in which case matrix hardness and deformation energy were expressed as second-order polynomial hydration rate constants. The effect of changes in pH of the hydration media on these parameters was also explored as part of the characterization process. Scanning electron microscopy and Fourier transform infrared spectroscopy were used to correlate the effect of synthesis variables on the micromechanical behavior PA 6,10 and its subsequent ability to impact drug release. The micromechanical values revealed that all independent formulation variables had a significant influence on the responses. Furthermore, the applied statistical model was utilized in selecting a combination of reaction variables to produce optional physicomechanical properties. The MR was selected for optimization among other parameters since it had a prominent effect on matrix integrity as well as drug release. The one-way analysis of variance, comparison of experimental versus fitted data, the R2 and P-values as well as the Durbin—Watson statistic indices were used in ascertaining the accuracy of the model. The rate-modulating drug release ability of synthetic aliphatic PA 6,10 was explored to direct the optimization using a higher resolution Box—Behnken statistical design. Constraints were set to obtain levels of independent variables that optimized the physicomechanical properties and the mean dissolution time fixed at eight hours.