Abstract
Solubility enhancement and thus higher bioavailability are of great importance and a constant challenge in pharmaceutical research whereby polymorph screening and selection is one of the most important tasks. A very promising approach for polymorph screening is solvent vapor annealing where a sample is exposed to an atmosphere saturated with molecules of a specific chemical/solvent. In this work, amorphous carbamazepine thin films were prepared by spin coating, and the transformation into crystalline forms under exposure to solvent vapors was investigated. Employing grazing incidence X-ray diffraction, four distinct carbamazepine polymorphs, a solvate, and hydrates could be identified, while optical microscopy showed mainly spherulitic morphologies. In vitro dissolution experiments revealed different carbamazepine release from the various thin-film samples containing distinct polymorphic compositions: heat treatment of amorphous samples at 80 °C results in an immediate release; samples exposed to EtOH vapors show a drug release about 5 times slower than this immediate one; and all the others had intermediate release profiles. Noteworthy, even the sample of slowest release has a manifold faster release compared to a standard powder sample demonstrating the capabilities of thin-film preparation for faster drug release in general. Despite the small number of samples in this screening experiment, the results clearly show how solvent vapor annealing can assist in identifying potential polymorphs and allows for estimating their impact on properties like bioavailability.
Highlights
The search for polymorphic crystal forms is necessary to identify favorable properties for various fields.[1−6] For active pharmaceutical ingredients (APIs), polymorphs should remain unchanged over the shelf-life time[7,8] and be compatible with excipients and processes, and their production has to be very reproducible.[9]
A very promising approach for polymorph screening is solvent vapor annealing where a sample is exposed to an atmosphere saturated with molecules of a specific chemical/solvent
Amorphous carbamazepine thin films were prepared by spin coating, and the transformation into crystalline forms under exposure to solvent vapors was investigated
Summary
The search for polymorphic crystal forms is necessary to identify favorable properties for various fields.[1−6] For active pharmaceutical ingredients (APIs), polymorphs should remain unchanged over the shelf-life time[7,8] and be compatible with excipients and processes, and their production has to be very reproducible.[9]. The usage of the drop casting technique in terms of printing yields high quality deposition of inks for newspaper, organic electronic materials for solar cells,[15] and transistors.[16] Even personalized medication could become reality soon.[17−21] Spin coating, dip coating, and vacuum deposition enable similar modifications to surfaces These deposition techniques are capable of adjusting the polymorphic form as well as the morphology; e.g., three different polymorphs of DH6T can be obtained by process parameter variation.[22] Phenytoin can be processed so that at least nine different morphologies can be set without changing the polymorph,[23] and even new polymorphs were found by Received: June 13, 2017 Accepted: August 24, 2017 Published: September 7, 2017
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