Screening of Sacrificial Excipients for Arresting Devitrification of Itraconazole from Solid Dispersion

The aim of the present investigation was to develop a solid dispersion of itraconazole (ITR) using sacrificial excipients like pregelatinized starch and spray-dried lactose alongside hydroxypropyl methylcellulose and Poloxamer 188, thereby arresting the conversion of the amorphous form of ITR to crystalline form, and to assess the dissolution stability of an amorphous form of the drug during short-term storage.

ITR-loaded solid dispersions were prepared by kneading. Formulation optimization was achieved by using a 2⁴ full factorial design on the basis of cumulative percent drug released at t₃₀, t₆₀, and t₁₂₀ min. An artificial neural network (ANN) was also applied as a statistical tool for obtaining better predictive ability and the outcomes of the ANN were compared with that of Design-Expert software.

The spectral data revealed no drug-carrier interactions. The P-X-ray diffraction study of the optimized batch showed a decrease in the crystallinity of drug as compared to the untreated drug. The in vitro dissolution studies of the optimized batch showed higher dissolution (92% at 120 min) in comparison to the other formulations. The dissolution stability study was performed at 40°C and 75% relative humidity for 90 days for the optimized formulation. The results of the optimized batch showed insignificant changes in cumulative percentage drug release during storage.

Dissolution stability could be attributed to the presence of sacrificial excipients as they tend to absorb moisture during storage and possibly get converted into crystalline form, thereby minimizing the recrystallization of ITR.