How Solvents Affect Acetaminophen Etching Pattern Formation:  Interaction between Solvent and Acetaminophen at the Solid/Liquid Interface

Abstract

The objective of this work was to further elucidate the dissolution process of acetaminophen crystals at the molecular level. The differences in the etching patterns from different solvents were used to study the interactions between solvent and acetaminophen molecules at the solid−liquid interface, such as solubilizing ability and potential solvent adsorption. The predicted etching patterns, based on the projections of attachment energies on the corresponding faces together with the solubilizing ability of the solvents, fit the observed etching patterns well. On the (001) face, the etching patterns were predominantly in the direction of the a-axis, which was also the direction of the dominant attachment energy. On the (110) face, the etching patterns were consistently in the direction of the c-axis irrespective of solvent used, and they were variable in other directions. These were well fit by the predicted etching patterns accounting for the different solubilizing ability of solvents. Both the most significant etching pattern deviations (on the (010) face) and the most significant morphology changes were observed with dichloroethane for acetaminophen. The morphology of acetaminophen crystals from different solvents showed that only the crystals from dichloroethane had significant elongation along the c-axis, which suggests the existence of stronger adsorption in the a-axis and b-axis directions than along the c-axis for dichloroethane. Overall, the current work suggests that the crystal interaction network, together with the interactions between solvent and acetaminophen, affects surface diffusion and plays an important role in the dissolution process.

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

“…Therefore the effects of polymeric additives on the dissolution of FFA cocrystals are attributed to surface adsorption of the polymers through specific interactions with the crystal surface, in particular, hydrogen bonding. [17][18][19][20]23,26,38,39 Among the polymers used in this study, PEG, containing a high percentage of hydrogen acceptors in the backbone, is the most hydrophilic, while PVP-VA, containing 40% acetate side chains in comparison to PVP, is the most hydrophobic. 11 Based on the dissolution experiment of the single FFA I crystal, the FFA I (100) face is more hydrophobic because it has a slower face dissolution rate in Figure 5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 COs were the only solid phase in Figure 9(b).…”

“…[17][18][19][20][21][22] When a polymer is present in solution, the polymer molecules can also be adsorbed on the surface of the dissolving crystal to form an adsorption layer, which affects solute bulk diffusion as well as surface diffusion.…”

Synergic Effects of Polymeric Additives on Dissolution and Crystallization of Acetaminophen

“…Previous study also showed that dissolution process has direction preference like crystallization process (3,20,26). Generally, the distance between two neighboring subunits in contact with the crystal surface should be very small, especially compared to the distance between two neighboring adsorbed small molecule additives at low concentration, and may be even smaller than the critical value r c (12).…”

“…After single acetaminophen crystals were prepared, the acetaminophen (010) face was acquired by cleaving single acetaminophen crystal and confirmed by X-ray powder diffraction (20). After one confirmed single crystal was mounted onto one AFM sample disk, the a-axis and c-axis directions were determined by observing the crystal two-dimension morphology.…”

“…Etching patterns were formed by dissolving crystal surface in short time by different solutions, and were determined by not only the supramolecular interactions within crystal itself, but also the interactions between adsorbed additives and crystal surface (8,20,24,26). It would be very interesting to check whether the dissolution pattern change in micro-level can be observed in its intrinsic dissolution rate (IDR), i.e.…”