This paper reports interactions and possible incompatibilities in solid dispersions of hydrophobic drugs with hydrophilic carriers, with solubility parameters employed as a means of interpreting results. Systems containing ibuprofen (IB) and xylitol (XYL) in varying proportions and systems of IB with other sugars and a sugar polymer were produced using solvent evaporation and fusion methods. Additionally, bridging agents were employed with IB/XYL systems to facilitate the production of a solid dispersion. Results show that IB formed no interactions with any of the sugar carriers but interacted with all the bridging agents studied. The bridging agents were immiscible with XYL in the liquid state. Results of other reported drug/carrier systems and those from the systems studied in this paper were interpreted using Hildebrand solubility parameters. A trend between differences in drug/carrier solubility parameters and immiscibility was identified with incompatibilities evidence when large solubility parameter differences exist between drug and carrier. It was concluded that Hildebrand parameters give an indication of possible incompatibilities between drugs and carriers in solid dispersions, but that the use of partial solubility parameters may provide a more accurate prediction of interactions in and between materials and could provide more accurate indications of potential incompatibilities.

To clarify earlier literature suggesting its existence in more than one solid form, carbamazepine dihydrate was prepared from individual anhydrous carbamazepine polymorphs I and III. The resultant materials were characterized by thermal and spectroscopic techniques, including variable-temperature Fourier transform (FT) Raman spectroscopy. On thermal dehydration, the carbamazepine dihydrates formed different anhydrous polymorphs depending on both starting material and dehydration conditions. Under conditions where liberated hydrate water cannot readily escape from around the sample, the dihydrate originating from polymorph III reverted to polymorph III, but under conditions of lower humidity/moisture, this dihydrate reverted to polymorph I. The dihydrate originating from polymorph I reverted to polymorph I irrespective of dehydration conditions. These observations could be due to a trace amount of nonhydrated original polymorph existing in the dihydrate phase that acts as a seed to regenerate the original polymorph under conditions where liberated hydrate water cannot readily escape from around the sample during dehydration. No evidence was generated that supported the existence of true polymorphs of carbamazepine dihydrate.