The aims of this systematic review are to explore the possibilities of using the positron annihilation lifetime spectroscopy (PALS) method in the pharmaceutical industry and to examine the application of PALS as a supportive, predictive method during the research process. In addition, the review aims to provide a comprehensive picture of additional medical and pharmaceutical uses, as the application of the PALS test method is limited and not widely known in this sector. We collected the scientific literature of the last 20 years (2002–2022) from several databases (PubMed, Embase, SciFinder-n, and Google Scholar) and evaluated the data gathered in relation to the combination of three directives, namely, the utilization of the PALS method, the testing of solid systems, and their application in the medical and pharmaceutical fields. The application of the PALS method is discussed based on three large groups: substances, drug delivery systems, and medical devices, starting with simpler systems and moving to more complex ones. The results are discussed based on the functionality of the PALS method, via microstructural analysis, the tracking of ageing and microstructural changes during stability testing, the examination of the effects of excipients and external factors, and defect characterization, with a strong emphasis on the benefits of this technique. The review highlights the wide range of possible applications of the PALS method as a non-invasive analytical tool for examining microstructures and monitoring changes; it can be effectively applied in many fields, alone or with complementary testing methods.

The relationship between the nanoscale free volume of pharmaceutical polymer films and their hydration behavior remains poorly understood. Eight pharmaceutical polymers were screened at three concentration levels within a quality-by-design framework; only two poly(vinyl alcohol) grades (PVA EG-30P and EG-40P), hydroxypropyl cellulose (HPC), and sodium alginate (Na-alginate) formed continuous films. These were characterized by positron annihilation lifetime spectroscopy (PALS), loss on drying (LOD), and swelling analysis. PALS clearly differentiated HPC, Na-alginate, and PVA, whereas the two PVA grades were similar and the concentration had only a minor effect. HPC showed the largest free volume holes (86.7–89.5 ų), and Na-alginate the smallest holes (36.9–39.6 ų) together with the highest LOD (20.2–21.6%). Across the 12 polymer–concentration combinations, the free volume hole volume correlated inversely with LOD (Spearman ρ = −0.85) but not with the equilibrium swelling index, as both HPC and Na-alginate swelled considerably more than PVA. Thus, PALS discriminates film-forming pharmaceutical polymers and reflects their residual water content, but the free volume of the air-dried films does not predict their swelling capacity.