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

Paul Christian,Anna Maria Coclite,Heike M.A Ehmann,Oliver Werzer

doi:10.1021/acsami.6b06015

Paul Christian, Anna Maria Coclite + Show 2 more

Open Access

https://doi.org/10.1021/acsami.6b06015

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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.

Highlights

Poor solubility and low bioavailability are major concerns in the formulation of several drug systems, limiting or even prohibiting their usage in practical application
The solid state transition from amorphous to crystalline clotrimazole films can be strongly altered by modifying the drug−air interface through a polymer encapsulation
The use of a solvent-free process in the deposition of the polymer layer circumvents any risk of solvent-induced solid state transitions in the drug or dissolution

Summary

Introduction

Poor solubility and low bioavailability are major concerns in the formulation of several drug systems, limiting or even prohibiting their usage in practical application. Experimental and theoretical studies have demonstrated this difference for some systems, including indomethacin[6,7] and ritonavir.[8] a significant drawback of the amorphous state is the lack of long time stability, which often results in undesired or unpredictable crystalline transition(s) over time This makes drug formulations with amorphous active pharmaceutical ingredients challenging.[9] The most common approach to prevent devitrification is the usage of solid dispersions, where the amorphous active pharmaceutical component (API) is dispersed within a carrier material.[5,10] While the definition comprises several different types of solid dispersions, it is mostly used to describe binary systems consisting of amorphous APIs within a polymeric carrier. Molecular interactions (e.g., hydrogen bonding)[12] or local entrapment within the matrix material can further stabilize the amorphous state.[13]

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