Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
Int J Pharm. 2010 May 31;391(1-2):79-89. doi: 10.1016/j.ijpharm.2010.02.023. Epub 2010 Feb 20.
This research focused on constructing and characterizing an optimized porosity-enabled amalgamated matrix (P-EAM) for sustained transbuccal drug delivery. An interphase, co-particulate, co-solvent, homogenization technique and lyophilization guided through a Box-Behnken experimental design was employed in the fabrication, characterization and optimization of 15 P-EAMs. The effects of varying factor levels on the characteristic in vitro physicochemical performances of the P-EAMs were explored. Formulations had an average weight of 128.44+/-3.48 mg with a dimensional size of 8mm by 5mm. Surface morphology showed varieties of pore structures, widespread distributions and uneven interconnectors. Satisfactory drug-loading was achieved (53.14+/-2.19-99.02+/-0.74%). Overall amount of drug released in 8h was measured by the MDT(50%) value which ranged between 22.50 and 225.00 min. Formulation demonstrated significant levels of ex vivo bioadhesive strength measured as detachment force (F(det)=0.964+/-0.015 to 1.042+/-0.025 N) and work of adhesion (omega(adh)=0.0014+/-0.00005 to 0.0028+/-0.00008 J). The potential of the P-EAMs to initiate and sustain ex vivo transbuccal permeation of drug was shown and measured as a cumulative value of between 25.02+/-0.85 and 82.21+/-0.57% in 8h. Formulations were mesoporous in nature with pore sizes ranging from 40 to 100 A characterized by the presence of interconnectors. Statistical constraints were simultaneously set to obtain levels of independent variables that optimized the P-EAM formulation.
本研究专注于构建和表征一种优化的多孔融合基质（P-EAM），以实现经颊持续药物输送。采用相间、共颗粒、共溶剂、均化技术和冷冻干燥法，通过 Box-Behnken 实验设计指导 15 种 P-EAM 的制备、表征和优化。研究了不同因素水平对 P-EAM 体外物理化学性能的影响。制剂的平均重量为 128.44±3.48mg，尺寸为 8mm×5mm。表面形态显示出各种孔隙结构、广泛分布和不均匀的连接体。实现了令人满意的载药量（53.14±2.19-99.02±0.74%）。通过 MDT（50%）值测量 8 小时内的总释放量，范围在 22.50 到 225.00min 之间。制剂表现出显著的体外生物黏附强度，表现为分离力（F(det)=0.964±0.015 到 1.042±0.025N）和黏附功（omega(adh)=0.0014±0.00005 到 0.0028±0.00008J）。P-EAM 具有启动和维持经颊体外药物渗透的潜力，并在 8 小时内测量为 25.02±0.85 到 82.21±0.57%的累积值。制剂具有中孔性质，孔径范围为 40 到 100A，特征是存在连接体。同时设定统计约束，以获得优化 P-EAM 配方的独立变量水平。
