PharmaChk: a decade of research and development towards the first quantitative, field-based medicine quality screening instrument.

Biomedical and clinical scientists play a major role in translating observations into interventions - therapeutics, diagnostics, and medical devices including screening instruments - that improve the health of individuals and the public. This path from observation to intervention is often long and beset with obstacles, many unanticipated. We believe that sharing concrete, real-word examples of scientists in academia moving along this path will highlight some of the types of challenges one may face; here we focus on an intervention being developed by the Zaman lab at Boston University - PharmaChk, the first quantitative, field-based instrument for medicine quality screening. Specifically, this paper describes the first ten years of scientific and engineering work towards the development of this instrument. Launched from a need observed by medicine quality scientists, the development of PharmaChk has required the integration of multiple technologies enabled by knowledge and expertise across diverse fields of science and engineering, including chemistry, ultrasonics, fluid dynamics, optics, computer science, and automation. These efforts have been shaped and driven by the many challenges we have faced and the technical, commercial, and financial support that we have received from many collaborators. By sharing this example, we hope to inspire our colleagues to pursue their own paths to new healthcare solutions.

Small volume method for drug release screening using ultrasonic agitation.

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.

Solid dissolution in a fluid solvent is characterized by the interplay of surface area-dependent diffusion and physical fragmentation.

The processes of dissolution and fragmentation have high relevance in pharmaceutical research, medicine, digestive physiology, and engineering design. Experimentally, dissolution and fragmentation are observed to occur simultaneously, yet little is known about the relative importance of each of these processes and their impact on the dissolution process as a whole. Thus, in order to better explain these phenomena and the manner in which they interact, we have developed a novel mathematical model of dissolution, based on partial differential equations, taking into consideration the two constituent processes of surface area-dependent diffusive mass removal and physical fragmentation of the solid particles, and the basic physical laws governing these processes. With this model, we have been able to quantify the effects of the interplay between these two processes and determine the optimal conditions for rapid solid dissolution in liquid solvents. We were able to reproduce experimentally observed phenomena and simulate dissolution under a wide range of experimentally occurring conditions to give new perspectives into the kinetics of this common, yet complex process. Finally, we demonstrated the utility of this model to aid in experiment and device design as an optimisation tool.