A Novel Cellulose-Based Hydrophilic Wafer Matrix for Rapid Bioactive Delivery

Abstract

A lyophilized polymeric wafer matrix was developed for rapid drug delivery via the oramucosal route. Lyophilization produced a porous wafer matrix that allowed simulated saliva (SS) to be rapidly absorbed into the hydrophilic structure. This surge of SS led to rapid disintegration of the wafer matrix. Hydroxypropylcellulose (HPC) was selected as the polymeric material based on its low gelatin potential. Other excipients incorporated into the system were lactose and mannitol as diluents, and glycine was utilized as a collapse inhibitor. A face-centered central composite design was employed to establish the significant effects of the independent formulation variables on the physico-chemical and physico-mechanical properties of the wafer matrix. The formulation variables investigated were, HPC concentration, diluent type and concentration, glycine concentration and fill volume. An analysis of these variables elucidated the influential factors that may be used to form an effective wafer matrix. HPC concentration significantly affected the wafer matrix disintegration rate ( P = 0.003), influx rate of SS ( P = 0.011) and wafer matrix friability ( P = 0.023). Diluent concentration had a significant effect on the wafer matrix tolerance ( P = 0.029) and wafer matrix friability ( P = 0.032). Statistical optimization was performed using constrained and artificial neural network techniques to predict ideal wafer formulation. Karl Fischer titrations revealed the reliability of the wafer matrices when small quantities of moisture were absorbed while being stored under ambient conditions.