Solubility parameters as predictors of miscibility in solid dispersions.
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.
Greenhalgh
D J
DJ
Drug Delivery Group, Postgraduate Studies in Pharmaceutical Technology, the School of Pharmacy, University of Bradford, BD7 1DP, U.K.
Williams
A C
AC
Timmins
P
P
York
P
P
D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D007052:Ibuprofen / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D014961:X-Ray Diffraction; D014993:Xylitol / Q000737:chemistry*
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002241:Carbohydrates; D003902:Detergents; D003911:Dextrans; D004337:Drug Carriers; D005079:Excipients; D012996:Solutions; D014993:Xylitol; D007052:Ibuprofen