Development and Characterization of Amorphous Nanofiber Drug Dispersions Prepared Using Pressurized Gyration

Abstract

Nanofibrous systems are attracting increasing interest as a means of drug delivery, although a significant limitation to this approach has been manufacture on a scale commensurate with dosage form production. However, recent work has suggested that nanofibers may be successfully manufactured on a suitable scale using the novel process of pressurized gyration (PG). In this study, we explore the potential of PG as a novel means of generating amorphous solid dispersions of poorly water-soluble drugs with enhanced dissolution performance. We examine the effect of increasing drug loading on fiber properties including size, surface characteristics, and the physical state of both components. Dispersions of ibuprofen in poly(vinylpyrrolidone) (PVP) were prepared (up to 50% w/w loading) and characterized using a range of imaging, thermal, diffraction, and spectroscopic techniques, while the release profiles were studied using sink and non-sink (pH 1.0) conditions. The drug was found to be dispersed on a molecular basis within the fibers; attenuated total reflection FTIR indicated evidence for a direct interaction between the drug and polymer at lower drug loading by the identification of a strong single band in the carbonyl region and amide region of ibuprofen and PVP respectively. Dissolution studies under sink conditions indicated a substantial increase in release rate, while non-sink studies showed evidence for supersaturation. It is concluded that PG presents a viable method for the production of drug-loaded nanofibers for oral administration with enhanced in vitro dissolution rate enhancement.

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…These are particularly used as a means to estimate the homogeneity of the mixture at a particular ratio, which is postulated to influence the stability of the resulted amorphous system. Among others, these include the calculation of the Hansen solubility parameters (104,126,146,154,161) and the Flory-Huggins theory (94,150). …”

“…Because the role of the excipients in the reviewed amorphous formulations was not limited to stabilizing the amorphous form, and because the roles were not specified in the reviewed articles, this was difficult to analyze (Fig. 5) (71–85,87,88,90–139,141–161,166,168–177). The polymers were most commonly (62%) used in solvent-based methods.…”

“…More uncommon preparation methods which are not widely used and established industrially for the preparation of amorphous formulations such as supercritical fluid impregnation /solvent-antisolvent (84,92,102,149), electrospinning /electrospraying (72,91,141,153,174), confined impinging jet (107) and pressurized gyration (161) have also been explored even though the applicability in large scale is still a question.…”

“…In the reviewed articles, no specific method was used in the investigation of amorphous solubility and dissolution behavior, even though different pharmacopoeia methods provide general guidance on how they should be performed. Ninety-two of the 101 studies reported solubility and dissolution studies (71–74,77–79,81–92,95,97–107,109–111,113–119,121,123,124,126–133,135–139,141–154,156,157,160,161,166,168–176). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only (148) or paired with confocal Raman microscopy (98), USP types I and II apparatus (72), USP type IV (152), closed loop of USP types II and IV (152), a perspex flow cell (73,142), a rotary mixer (131), a Chinese pharmacopoeia type III apparatus (118), an in-house miniaturized USP type II apparatus (175), Sirius T3 apparatus (146), μFLUX dissolution-permeation apparatus (141), Raman UV-Vis flow cell system (99), a centrifuge (88), high throughput screening using a 96-well plate (82,115,157), Wood’s apparatus (99,137), an orbital shaking incubator (156), and another shake-flask method (171) (Fig.…”

“…Likewise, the media reported were mainly different types of a simple buffers such as treated water (i.e. deionized, degassed, distilled, purified), HCl, and phosphate/acetate buffers at pHs ranging from 1.2 to 7.4 (71–74,77–79,81–88,90–92,95,100–107,109–111,113–119,121,126,127,129–133,135–139,149,150,153,154,156,160,161,166,168–177). Among the 88 studies that reported a dissolution assay, only sixteen (~18%) used a biorelevant dissolution medium (BDM) such as simulated gastrointestinal fluids and simulated saliva (77,79,82,97,121,123,130,135,136,145,152,154,160,169,170,176).…”