Supersaturated Isotretinoin: Scrutiny into Solid States Attributes

Background/Objectives: The formulation development of Isotretinoin (ISN) is limited by its solubility and stability issues. This study aimed to characterise the BCS class II drug ISN, particularly the possible different solid state and formulate amorphous solid dispersion aiming for a supersaturation state. Methods: ISN's physical states are investigated in its raw form, quench-cooled form, physical mixture with the polymer and corresponding solid dispersion form. Quench-cooled ISN was prepared in situ using DSC. Carrier stabilisation of ISN was attempted using the solid dispersion technique. Hereby, the solid dispersion of drug-polymer PVPVA at a ratio of 1:3 was prepared using the solvent evaporation method. Solid dispersion, physical mixture and raw ISN were characterised for the saturated solubility. Physical characterisation of the samples was performed using DSC, ATR-FTIR and a light microscope. Results: Two polymorphs of ISN (forms I and II) were found in the raw ISN, with form II being thermodynamically more stable. ISN possesses strong crystallinity and resistance to amorphisation under the applied quench-cooling condition without the presence of a carrier system. The conjugated polyene structure in ISN contributes to the polymorphic transformation and isomerisation. The incorporation of PVPVA in the solid dispersion system successfully improved the water solubility (sixfold) of ISN despite a combination of crystalline and amorphous components being present in the system. Conclusions: ISN is a class II drug crystal molecule. Taking advantage of solubility and possibility in the polymorphic transformation of ISN in a binary system, we concluded that ISN could potentially be formulated into its corresponding crystalline solid dispersion form.