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1  Department of Pharmacy, School of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

Abstract: Well established techniques for increasing the solubility of poorly water soluble APIs are available. However, formulating highly water soluble APIs into dosage forms exhibiting modified release profile is gaining interest. In this work a new application for Soluplus®, a graft copolymer, is launched. A novel approach where Soluplus® is used as a dissolution modifying agent for highly water soluble APIs is introduced. Acetaminophen (APAP) and guaifenesin (GF) were used as model water soluble APIs. 95:5 and 90:10 ratios of respective API and Soluplus® were either physically mixed (PM) together or melted together on a hot plate. Melts were investigated using DSC and XRPD and compacts were submitted to dissolution studies. In case of APAP:Soluplus® a single melting event with an onset similar to pure APAP was determined by DSC. The XRPD diffractogram of molten material exhibited an amorphous halo, however further processing caused the material to crystallize. The compacts made of ground molten materials had a similar release profile and showed a slower release compared to compacts prepared from PMs. When GF:Soluplus® melts were submitted to DSC a single melting event occurred. The onset of this event did not match with the melting event of pure GF. The XRPD diffractogram of the molten samples revealed that a new polymorphic form of GF had crystallized. GF:Soluplus® compacts made of molten material revealed faster release of GF compared to compacts made of PMs of GF:Soluplus®. Using Soluplus® as a dissolution modifying agent enables tailoring of the release of the API. In this work the release of two highly water soluble APIs was modified by two different methods. Furthermore, presence of a new polymorphic form of GF was identified.
Keywords: solid dispersion, Soluplus®, polymorphism, water soluble APIs, modified release