Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Analyst. 2018 Sep 24;143(19):4732-4740. doi: 10.1039/c8an00881g.
Drug release testing plays a major role along all parts of the dosage form development and manufacturing process. However, official methods to perform this type of testing are often resource intensive and require highly specialized facilities. Affordable and accessible methods for studying drug release behavior are currently lacking. This work presents a small volume approach to solid dissolution and drug release testing of solid dosage forms using ultrasonic agitation. Cavitation and acoustic streaming were generated by a microprobe horn delivering a 40 kHz acoustic signal into a 50 mL test vessel. These two phenomena resulted in breakdown of and release of drug from tablet samples. Prednisone Performance Verification Tablets were used as model tablets to study the effect of system parameters on the drug release process. The effects of these parameters on the acousto-hydrodynamic environment were studied using streak photography and hydrophone measurements. Drug release behavior showed a slow/fast threshold transition separated by a highly variable regime as a function of the system parameters. Observations from drug release experiments and results from acoust-hydrodynamic characterization experiments suggested that this transition is dominated by acoustic streaming. This method represents a screening method to probe relative differences in dosage form composition and acts as a complimentary approach to official testing methods. The small volume format of this test has potential applications in the study of drug release properties from low-dose and novel solid dosage forms as well as reduced cost and increased accessibility of release testing for post-manufacturing tablet quality screening, a current need in low- and middle-income countries.
药物释放测试在整个剂型开发和制造过程中都起着重要作用。然而,执行这种类型测试的官方方法通常需要大量资源,并需要高度专业化的设施。目前缺乏研究药物释放行为的经济实惠且易于获取的方法。本工作提出了一种使用超声波搅拌进行固体溶解和固体剂型药物释放测试的小体积方法。通过微探头喇叭将 40 kHz 的声信号送入 50 mL 测试容器中,产生空化和声波流。这两种现象导致片剂样品中的药物崩解和释放。泼尼松性能验证片被用作模型片剂,以研究系统参数对药物释放过程的影响。使用条纹摄影和水听器测量研究了这些参数对声 - 水动力环境的影响。药物释放行为表现出缓慢/快速阈值转变,其特征是高度可变的状态,这是系统参数的函数。药物释放实验的观察结果和声学 - 水动力特性实验的结果表明,这种转变主要由声波流主导。该方法代表了一种筛选方法,可用于探测剂型组成的相对差异,并作为官方测试方法的补充方法。这种测试的小体积格式有可能应用于低剂量和新型固体剂型的药物释放特性研究,以及降低成本和提高药物释放测试的可及性,以用于制造后片剂质量筛选,这是低收入和中等收入国家的当前需求。