CAJ | 학술논문

针对球形扩散控制体系中的药物释放，通过建立数学模型，借鉴反问题求解思路，利用混合Newton-Tikhonov正则化方法，优化体系中初始药物浓度分布以及扩散系数分布，实现不同的目标药物释放。在固定扩散系数条件下，优化了实现拟恒速、速率线性降低及先增后恒速的非线性释放目标的初始药物浓度分布；还优化了不同初始药物浓度分布条件下的体系扩散系数分布，以期达到拟恒速释放。研究表明：通过优化球形基质体系中药物的初始浓度分布或扩散系数分布，体系的药物释放可达到释放的目标要求；通过简单的外层无/少药物负载的初始浓度设计，优化扩散系数的体系可有效解决“突释”问题。
침대구형확산공제체계중적약물석방，통과건립수학모형，차감반문제구해사로，이용혼합Newton-Tikhonov정칙화방법，우화체계중초시약물농도분포이급확산계수분포，실현불동적목표약물석방。재고정확산계수조건하，우화료실현의항속、속솔선성강저급선증후항속적비선성석방목표적초시약물농도분포；환우화료불동초시약물농도분포조건하적체계확산계수분포，이기체도의항속석방。연구표명：통과우화구형기질체계중약물적초시농도분포혹확산계수분포，체계적약물석방가체도석방적목표요구；통과간단적외층무/소약물부재적초시농도설계，우화확산계수적체계가유효해결“돌석”문제。
This work presents an optimization approach for achieving desirable drug release from diffusion-controlled spherical devices. A mathematical model was established for description of drug release in these devices. Initial drug concentration and diffusivity profiles were optimized using a mixed Newton-Tikhonov regularization method to study various targeted release performances. Pseudo constant release, linear decrease release and linear increase followed by a constant release profiles were achieved under constant diffusivity with optimized initial drug concentration distributions, while the diffusivity profiles in devices with different initial concentration profiles were optimized to establish a pseudo constant release profile. The results show that the targeted drug release in the spherical devices can be fulfilled by optimizing the initial drug concentration or diffusivity profile. Moreover, burst effects could be minimized by maintaining low or no drug at the outer layer of the spherical devices with optimized diffusivity profiles.