Nanomechanical testing in drug delivery: Theory, applications, and emerging trends

Recent Advances in Nanomechanical Measurements and Their Application for Pharmaceutical Crystals

“…could also be important to validate the experimentally obtained values and errors. Nanoindentation technique and increased computational power with precise calculations of mechanical properties can facilitate huge developments in this interdisciplinary subject. − ,− ,, Further, detailed studies on the fatigue and creep of pharmaceutical crystals using nanoindentation are not much explored. These studies provide crucial knowledge about the time-dependent plasticity and activation energies at the elastic–plastic deformation points.…”

“…Nanoindentation is a quantitative technique for the measurement of the mechanical behavior of small-volume molecular or pharmaceutical crystals. − ,,, Such a technique has become relevant to crystal engineering as it can quantify the relative strengths of intermolecular interactions, molecular arrangement, and crystal anisotropy and can establish structure–property relationships. Desiraju and co-workers have thoroughly developed an understanding of structure–mechanical properties correlations by utilizing the nanoindentation technique .…”

“…18,68−70 Nanoindentation is widely recognized as the preferred method to investigate the mechanical behavior of a wide range of molecular crystals including organic, pharmaceutical, and inorganic with emphasis on structure−property relationships. 10−12,19,20,62,71−74 The basic understanding of molecular-level properties [10][11][12]19,20,62 such as interactions characteristics, 75−77 crystal anisotropy, 78−82 molecular arrangement, 10−12,83−85 layer migration, 30,31,86 desolvation, 79,87 mechanoluminescence, 42 photochemical reactions, 88 domain coexistence, 30,89,90 self-healing behavior, 91 thermoresponsive behavior, 92,93 solid-solution hardening, 94,95 and solid-state reactivity 88,93,96 can be investigated using nanoindentation.…”

“…Mechanical behavior of pharmaceutical crystals largely governs the load-driven process development at different stages of tablet formulation for drug products including flowability, milling (wet and dry), grinding, filtration, crushing, and powder compaction. − To interpret how crystalline pharmaceutical materials perform during these load-driven processes, it is of utmost importance to understand crystal structure–mechanical property relationships of pharmaceutical drugs which can evidently be established by testing and measurement of mechanical behavior of pharmaceutical crystals. − A proper understanding of mechanical behavior such as elastic or plastic deformations of crystalline active pharmaceutical ingredients (APIs) is much required during the manufacturing and production in the pharmaceutical industry. − Production of durable and stable tablets of pharmaceutical drugs predominately depends upon the degree of plastic deformation of its crystals under applied external load. − Broadly, the two crucial facts need to be analyzed to understand the compaction behavior of crystalline pharmaceutical materials. , First, the plasticity in crystalline drugs is important to increase the interparticulate contact area and binding during compaction that causes an improved tabletability. Second, in the case of the excessive plasticity in a drug with very low hardness ( H ), it would be extremely difficult to mill or grind the drug as it can turn into a paste during milling, which can adversely affect the tablet production stages of APIs; for example, voriconazole (VOR) is very difficult to mill due to its soft nature .…”

Cytosine monohydrate under mechanical stress

“…Recognizing that cooperative molecular motion over multiple unit cells and large cell volume changes raises mechanical considerations, the nanomechanical properties of CM are the focus of the current study. The mechanical behavior of molecular crystals has been the subject of much interest [15][16][17][18][19][20][21][22] with nanoindentation methods [23][24][25] in particular emerging as an important tool for evaluating the plasticity or elasticity of single crystals, calculating fundamental parameters such as hardness and modulus, and establishing the relationship between structure and anisotropic behavior.…”