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

Abstract

Keywords:oral drug delivery amorphous solid dispersion dissolution crystallization nanotechnology tableting chemical stability Raman spectroscopy a b s t r a c t 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.

Characterization of Synthesized and Commercial Forms of Magnesium Stearate Using Differential Scanning Calorimetry, Thermogravimetric Analysis, Powder X-Ray Diffraction, and Solid-State NMR Spectroscopy

“…), [1][2][3][4] while too much lubricant can lead to bioavailability issues (poor dissolution, etc.). [4][5][6] One of the most widely used lubricants is magnesium stearate (MgSt). It is found in 108 of the top 200 formulations currently in the market, due to its ability to decrease friction between the tablet and the die during tabletting.…”

Scale‐up of electrospinning technology: Applications in the pharmaceutical industry

“…A few examples can be found in the literature where fibrous mats are processed into conventional tablets via a traditional process (milling followed by homogenization with excipients and compression; Démuth et al, ; Démuth et al, ; Sebe, Bodai, et al, ; Szabó, Kállai‐Szabó, Sebe, & Zelkó, ). Generally, the properties of the prepared blends (particle size distribution, flowability) and tablets (hardness, friability, disintegration time, dissolution) are examined and published.…”

“…As the ground fibers form a gelling network, disintegration is hindered when the amount of excipients (especially fillers) is small. In spite of the low bulk density and the relatively poor flowability, rotary tableting could be carried out and tablets with acceptable weight variation could be obtained (Démuth, Farkas, Balogh, et al, ). To process a nonwoven sheet to tablets in a continuous manner also seems feasible, which could potentially be a really important feature in the future (Szabó et al, ).…”

Electrospun amorphous medicated nanocomposites fabricated using a Teflon-based concentric spinneret

“…They have an amorphous physical state and can effectively retard the recrystallization of drugs when they are transferred into amorphous composites (6). One example is polyvinylpyrrolidone (PVP), broadly reported to create drug-loaded composites to improve the dissolution rates of poorly water-soluble drugs (7)(8)(9)(10). However, PVP is a synthetic polymer.…”