Polymer Encapsulation of an Amorphous Pharmaceutical by initiated Chemical Vapor Deposition for Enhanced Stability

Abstract

The usage of amorphous solids in practical applications, such as in medication, is commonly limited by the poor long-term stability of this state, because unwanted crystalline transitions occur. In this study, three different polymeric coatings are investigated for their ability to stabilize amorphous films of the model drug clotrimazole and to protect against thermally induced transitions. For this, drop cast films of clotrimazole are encapsulated by initiated chemical vapor deposition (iCVD), using perfluorodecyl acrylate (PFDA), hydroxyethyl methacrylate (HEMA), and methacrylic acid (MAA). The iCVD technique operates under solvent-free conditions at low temperatures, thus leaving the solid state of the encapsulated layer unaffected. Optical microscopy and X-ray diffraction data reveal that at ambient conditions of about 22 °C, any of these iCVD layers extends the lifetime of the amorphous state significantly. At higher temperatures (50 or 70 °C), the p-PFDA coating is unable to provide protection, while the p-HEMA and p-MAA strongly reduce the crystallization rate. Furthermore, p-HEMA and p-MAA selectively facilitate a preferential alignment of clotrimazole and, interestingly, even suppress crystallization upon a temporary, rapid temperature increase (3 °C/min, up to 150 °C). The results of this study demonstrate how a polymeric coating, synthesized directly on top of an amorphous phase, can act as a stabilizing agent against crystalline transitions, which makes this approach interesting for a variety of applications.

Strategies for Drug Encapsulation and Controlled Delivery Based on Vapor‐Phase Deposited Thin Films

“…All the above‐mentioned vapor‐phase processes operate at low temperatures, with the consequence that also delicate substrates such as plastic or paper can be easily coated. Particularly in the field of drug encapsulation, this is a great advantage, since it allows also the coating of thin molecular layers of drugs, without evaporation due to high processing temperatures and without inclusion of solvents, with the only requirement being that the drug needs to sustain the mild vacuum . Multilayered structures can also be easily obtained by vapor‐phase methods (see Fig.…”

“…Encapsulation of amorphous drugs has been investigated in details also with iCVD polymers by Christian et al Three different polymer compositions were deposited by iCVD on top of amorphous clotrimazole films to study the stability of the drug solid state: two different stimuli‐responsive polymers, poly(2‐hydroxyethyl methacrylate) [p‐HEMA], hydrogel, and poly‐(methacrylic acid) [p‐MAA], pH‐responsive, and a non‐responsive hydrophobic fluorinated polymer, poly(perfluorodecyl acrylate) [p‐PFDA] . In their study, the authors compare the effect of different polymer chemistries on the stability of the amorphous clotrimazole by means of optical microscopy and X‐ray diffraction (Figure a).…”

“…As afore‐mentioned, such an encapsulating shell often acts then as diffusion membrane in order to have a timed release and/or as protective barrier, which allows the drug release to occur when specific conditions are met (e.g., barrier disintegration at a specific site in the body). Several vapor phase techniques have been employed for the direct encapsulation of drugs or drug loaded media, taking into account the possibility to treat a vast variety of substrates, such as solid surfaces, nanostructured/engineered surfaces, particles, but also on delicate substrates like amorphous drug films or liquid thin films …”

Manipulating drug release from tridimensional porous substrates coated by initiated chemical vapor deposition

“…In general, the CVD techniques are rather harsh in terms of process conditions (e.g., temperature, vacuum) so that delicate surfaces might suffer during synthesis. Recently, CVD on delicate substrates has successfully been demonstrated by initiated CVD (iCVD) . In iCVD processes, a sacrificial molecule, the initiator, is thermally activated by using a very low energy input, enabling modification on any surface, even liquid ones.…”

“…The former swells in water and is a widely used synthetic hydrogel for various biomedical applications due to its biocompatibility . P‐MAA is characterized by a pH‐dependent swelling …”