Modelling and shadowgraph imaging of cocrystal dissolution and assessment of in vitro antimicrobial activity for sulfadimidine/4-aminosalicylic acid cocrystals

详细信息    查看全文

• 作者：Dolores.R. Serrano^a ; Tim Persoons^b ; Deirdre M. D'Arcy^a ; Carolina Galiana^c ; Maria Auxiliadora Dea-Ayuela^c ; Anne Marie Healy^a ; ^{healyam@tcd.ie" class="auth_mail" title="E-mail the corresponding author}
• 关键词：4-ASA ; 4-Aminosalicylic acid ; AI ; Aggregation index ; BFDH morphology ; Bravais ; Friedel ; Donnay and Harker morphology ; DVS ; Dynamic vapour sorption ; FTIR ; Fourier-transformed infrared ; PI ; Polymorph I ; PII-HI ; Polymorph II &mdash ; Habit I ; PII-HII ; Polymorph II &mdash ; Habit II ; PII-HIII ; Polymorph II &mdash ; Habit IIII ; PII-HIV ; Polymorph II &mdash ; Habit IV ; PM ; Physical mixture ; PSD ; Particle size distribution ; PXRD ; Powder X-ray diffraction ; RH ; Relative humidity ; SDM ; Sulfadimidine ; SEM ; Sca
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：30 June 2016
• 年：2016
• 卷：89
• 期：Complete
• 页码：125-136
• 全文大小：1831 K

文摘

The aim of this work was to evaluate the influence of crystal habit on the dissolution and in vitro antibacterial and anitiprotozoal activity of sulfadimidine:4-aminosalicylic acid cocrystals.

Methods

Cocrystals were produced via milling or solvent mediated processes. In vitro dissolution was carried out in the flow-through apparatus, with shadowgraph imaging and mechanistic mathematical models used to observe and simulate particle dissolution. In vitro activity was tested using agar diffusion assays.

Results

Cocrystallisation via milling produced small polyhedral crystals with antimicrobial activity significantly higher than sulfadimidine alone, consistent with a fast dissolution rate which was matched only by cocrystals which were milled following solvent evaporation. Cocrystallisation by solvent evaporation (ethanol, acetone) or spray drying produced flattened, plate-like or quasi-spherical cocrystals, respectively, with more hydrophobic surfaces and greater tendency to form aggregates in aqueous media, limiting both the dissolution rate and in vitro activity. Deviation from predicted dissolution profiles was attributable to aggregation behaviour, supported by observations from shadowgraph imaging.

Conclusions

Aggregation behaviour during dissolution of cocrystals with different habits affected the dissolution rate, consistent with in vitro activity. Combining mechanistic models with shadowgraph imaging is a valuable approach for dissolution process analysis.