Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion

• Published in: Journal of pharmaceutical sciences Vol. 105; no. 9; pp. 2982 - 2988
• Main Authors: Démuth, Balázs, Farkas, Attila, Balogh, Attila, Bartosiewicz, Karolina, Kállai-Szabó, Barnabás, Bertels, Johny, Vigh, Tamás, Mensch, Jurgen, Verreck, Geert, Van Assche, Ivo, Marosi, György, Nagy, Zsombor K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016
• Subjects: amorphous; Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; chemical stability; Chemistry, Pharmaceutical; Crystallization; dissolution; Drug Compounding; Excipients; Itraconazole - administration & dosage; Itraconazole - chemistry; Lubricants - chemistry; nanotechnology; oral drug delivery; Raman spectroscopy; solid dispersion; Solubility; Spectrum Analysis, Raman; Stearic Acids - chemistry; tableting; Tablets; chemical stability; amorphous; solid dispersion; oral drug delivery; dissolution; crystallization; nanotechnology; tableting; Raman spectroscopy
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2016.04.032

Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation is in a quite early phase. Development of high speed electrospinning opened up the possibility to study tableting of electrospun solid dispersions (containing polyvinylpyrrolidone-vinyl acetate and itraconazole [ITR] in this case). This work was conducted to investigate the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting. The dissolution rates from tablets proved to be mainly composition dependent. Magnesium stearate acted as a nucleation promoting agent (providing an active hydrophobic environment for crystallization of ITR) hindering the total dissolution of ITR. This crystallization process proved to be temperature dependent as well. However, the extent of dissolution of more than 95% was realizable when a less hydrophobic lubricant, sodium stearyl fumarate (soluble in the medium), was applied. Magnesium stearate induced crystallization even if it was put in the dissolution medium next to proper tablets. After optimization of the composition, scaled-up tableting on a rotary press was carried out. Appropriate dissolution of ITR from tablets was maintained for 3 months at 25°C/60% relative humidity. HPLC measurements confirmed that ITR was chemically stable both in the course of downstream processing and storage.