Spray drying ternary amorphous solid dispersions of ibuprofen - An investigation into critical formulation and processing parameters.

A design of experiment (DoE) approach was used to investigate the critical formulation and processing parameters in spray drying ternary amorphous solid dispersions (ASDs) of ibuprofen. A range of 16 formulations of ibuprofen, HPMCP-HP55 and Kollidon VA 64 were spray dried. Statistical analysis revealed the interrelation of various spray drying process conditions and formulation factors, namely solution feed rate, inlet temperature, Active Pharmaceutical Ingredient (API)/excipients ratio and dichloromethane (DCM)/methanol (MeOH) ratio. Powder X-ray diffraction analysis (PXRD) showed that all the samples with the lowest API/excipient ratio (1:4) were amorphous, while others were crystalline. Moreover, differential scanning calorimetry (DSC) analysis was employed to investigate ASD formulation more in-depth. The glass transition temperatures (Tg) of all ASDs were in the range 70-79°C, while crystalline formulations displayed an endothermic peak of melting of crystalline ibuprofen in the range of 50-80°C. The high Tg of ASDs was an indication of highly stable ASD formulations as verified via PXRD at zero day and afterward at 1, 1.5, 3 and 6month intervals. The intermolecular interactions between ibuprofen molecule and excipients were studied by Fourier transform infrared spectroscopy (FTIR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. FTIR and Carbon-13 ssNMR analysis indicated that hydrogen bond formation involving the carboxyl group in ibuprofen within the ASDs is likely. More importantly, the solubility of ibuprofen in ASD formulations is improved compared to pure ibuprofen. This was due to both the amorphous structure of ibuprofen and of the existence of amphiphilic excipient, Kollidon VA 64, in the formulation.

Ziaee A ，Albadarin AB ，Padrela L ，Faucher A ，O'Reilly E ，Walker G ... -  《-》

Design of spray dried ternary solid dispersions comprising itraconazole, soluplus and HPMCP: Effect of constituent compositions.

A range of 17 ternary formulations of itraconazole (ITZ), HPMCP and Soluplus have been manufactured using spray drying. These amorphous solid dispersions (ASDs) were very stable against crystallisation and ITZ was found to be amorphous in all formulations after one year at 40°C/75% RH. A number of solid state analytical techniques including PXRD, DSC, small angle X-ray scattering, FTIR and solid state NMR were used to characterise the physicochemical properties of the ASDs following processing and storage and to assess any interactions between components. Microtrac laser scattering analysis revealed a relationship between polymer levels and particle size distribution (PSD). Dissolution studies indicated that higher Soluplus content in the formulation resulted in higher concentrations of ITZ in acidic media.

Davis MT ，Potter CB ，Mohammadpour M ，Albadarin AB ，Walker GM ... -  《-》

Characterization of Phase Separation Propensity for Amorphous Spray Dried Dispersions.

McNamara D ，Yin S ，Pan D ，Crull G ，Timmins P ，Vig B ... -  《-》

A comparison of spray drying and milling in the production of amorphous dispersions of sulfathiazole/polyvinylpyrrolidone and sulfadimidine/polyvinylpyrrolidone.

Caron V ，Tajber L ，Corrigan OI ，Healy AM ... -  《-》

Investigation into Intermolecular Interactions and Phase Behavior of Binary and Ternary Amorphous Solid Dispersions of Ketoconazole.

Sarpal K ，Tower CW ，Munson EJ 《-》