Surface modification of acetaminophen particles by atomic layer deposition

Abstract

Active pharmaceutical ingredients (APIs) are predominantly organic solid powders. Due to their bulk properties many APIs require processing to improve pharmaceutical formulation and manufacturing in the preparation for various drug dosage forms. Improved powder flow and protection of the APIs are often anticipated characteristics in pharmaceutical manufacturing. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD, utilizing common chemistries for Al2O3, TiO2 and ZnO, is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating process and maintains its stable polymorphic structure. Acetaminophen with nanometer scale ALD coatings shows slowed drug release. ALD TiO2 coated acetaminophen particles show cytocompatibility whereas those coated with thicker ZnO coatings exhibit the most cytotoxicity among the ALD materials under study when assessed in vitro by their effect on intestinal Caco-2 cells.

Mathematical Modelling of Acetaminophen Release in HPC/PAAm Hydrogel: Synthesis and Application

“…Finally, between 800 and 860 cm -1 , the substituted benzene ring in the paraposition is observed. These peaks were previously reported in [32].…”

“…From Figure 8 can be observed, besides, that the acetaminophen is stable until some point between 200 and 300°C, and after that, its loss of mass increases rapidly. This was also reported in [32]. Additionally, the thermal degradation for the HPC/PAAm gel is similar to that of the hydroxyproyl methyl cellulose/polyacrylamide polymer, with weight losses due to humidity content and the degradation of the cellulosic polymer at 250°C, while the degradation of the polyacrylate was observed in the 350°C range [38,39].…”

“…On the other hand, in the thermogram of the HPC/PAAm gel with incorporated acetaminophen, a well-defined exothermic peak at 172°C is observed. In [32], a peak of acetaminophen close to 170°C was reported, which allows us to deduce that the peak in Figure 5 corresponds to acetaminophen. According to [33], fully miscible systems of two compounds present a single T g , even when each compound in the composite has its own T g .…”

“…The other one consists in irregular prims with columnar growth in the planes {110}, {201}, {001}, and {011} and with no agglomerates, which indicates that the acetaminophen was crystallized on the surface of the HPC/PAAm gel and not between its internal chains. Irregular acetaminophen prisms were also reported in [32]. Besides, other polymers have also presented drug crystallization on the surface.…”

Oriented Attachment and Nanorod Formation in Atomic Layer Deposition of TiO2 on Graphene Nanoplatelets

“…4 Although mostly developed for flat substrates, ALD is also scalable to high-surface-area substrates, which are relevant for a variety of applications spanning catalysis, energy storage and conversion, and medicine. 2,5−16  Given its unparalleled precision and scale-up potential, considerable research effort has been put in expanding its capability to the deposition of nanostructures other than thin films such as nanoparticles (NPs). 2,6,7,17−21 However, the formation and growth of NPs are mediated not only by ALD surface chemistry but also by nonequilibrium phenomena such as adatom and NP diffusion and aggregation.…”