A review of the state-of-the-art: progress in ultrasonic and acoustic techniques for quality assessment in the development and manufacturing of oral solid dosage forms - Part I: theoretical foundations and principles.

Over the past two decades, a diverse array of ultrasonic and acoustic elastic-wave techniques has been developed to non-destructively assess macro- and micro-scale properties of compressed Oral Solid Dosage (OSD) forms. These methods are increasingly recognized for their potential roles in formulation design, process development, quality evaluation, and product release. This review is presented in two parts: Part I focuses on the theoretical foundations and principles of ultrasonic and acoustic techniques, while Part II will address their practical applications and emerging directions. This article (Part I) provides a comprehensive theoretical framework for understanding the physical basis of these techniques and their relevance to pharmaceutical quality assurance. Beginning with elastic wave theory in heterogeneous, granular media, the review explores how wave phenomena-such as dispersion, attenuation, and scattering-are intrinsically linked to microstructural and mechanical features, including porosity, viscoelasticity, interparticle bonding, and subsurface defects. Emphasis is placed on the functional relationships between ultrasonic parameters and Critical Quality Attributes (CQAs) as defined within the Quality by Design (QbD) paradigm. The article distinguishes between hard (direct) and soft (model-based) sensing approaches, situating ultrasonic methods alongside complementary technologies such as Near-Infrared (NIR) spectroscopy, Raman spectroscopy, X-ray Computed Tomography (CT), and Terahertz imaging. The review also examines key instrument configurations and transducer technologies, ranging from piezoelectric contact probes to non-contact laser and air-coupled systems, as well as waveform acquisition and signal processing strategies used to extract mechanical and geometric properties. Together, these theoretical principles lay the groundwork for the effective integration of ultrasonic methods into intelligent, real-time pharmaceutical manufacturing environments.