Allababidi S, Shah J C
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Pharm Sci. 1998 Jun;87(6):738-44. doi: 10.1021/js9703986.
The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.
本研究的总体目标是设计一种基于单硬脂酸甘油酯（GMS）的可植入给药系统，用于抗生素的局部给药，以预防手术伤口感染。为了设计该植入物，必须开发一种能模拟体内植入条件的释放方法，以便能够预测植入物在实际体内使用时的释放特性。此外，确定释放动力学和机制，并评估影响基于GMS的基质中药物释放的因素，对于进一步设计能够产生所需释放速率的植入物是必要的。通过将头孢唑林从植入琼脂凝胶的GMS基质中释放出来进行监测，琼脂凝胶在粘度和含水量方面模拟皮下组织。凝胶法导致观察到植入物紧邻区域的空间和时间浓度分布，表明局部给药的益处；然而，凝胶法或小瓶释放法的累积释放曲线之间没有显著差异。用小瓶法从基于GMS的基质中释放头孢唑林遵循Higuchi的时间平方根动力学。发现释放速率与头孢唑林负载量（A）和基质的表面积（SA）成正比，由以下方程表示：= 0.24ASA。基于该方程，可以设计出各种能产生所需释放速率或释放持续时间的GMS基质。这也表明头孢唑林的释放遵循从不溶性基质中自由溶解药物的释放动力学，因此它是一个扩散控制过程。通过比较水溶性差的环丙沙星（0.16 mg/mL）和水溶性高的头孢唑林（325 mg/mL）的释放动力学，确定了药物溶解度对释放动力学的影响。从相同的GMS基质中，环丙沙星的释放持续时间（80小时）比头孢唑林（25小时）长。尽管环丙沙星的释放最初受基质控制，但由于其溶解度差，搅拌加速了基质的崩解和释放，并且环丙沙星的释放似乎是遵循零级释放动力学的溶解控制过程。
