In situ amorphisation of indomethacin with Eudragit® E during dissolution

Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers

“…The XRD and DSC results confirm that most of the loaded drug remains amorphous in these polymeric matrices at 20 wt.% drug loading level. These results are consistent with previously reported thresholds of drug loading level in IND-polymer ASD systems above which amorphous-to-crystalline transition tends to occur:~34 wt.% in PHEMA [8], 30-40 wt.% in PVP [18], N30 wt.% in Soluplus [19], N33.3 wt.% in ethylcellulose/HPMC (1:1) [20], and 25-50 wt.% in Eudragit E100 [21,22].…”

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…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.…”

“…The majority of the studies used a large volume of medium (≥250 ml), which can indirectly be translated to the equally large amounts of materials required in practice. Depending on the condition selected (sink or non-sink), weight of samples between 5–1800 mg were reported (72,74,77–79,83–85,87,90,91,95,100,105,106,109–111,114,116,121,126,128,130,135,136,138,149,154,166,170). Interestingly, the use of small-scale or miniaturized in vitro dissolution methods is still limited.…”

Design of chitospheres loaded with pristine polymer particles for extended drug delivery via polyelectrolyte complexation and particulate leaching

“…The anti-inflammatory drug, indomethacin, is a BCS class II drug with good permeability and poor aqueous dissolution that limits its bioavailability (Obitte et al, 2014). Transition changes of indomethacin from crystalline to amorphous states within the loaded chitospheres may potentially improve its solubility and hence enhance bioavailability (Yuksel et al, 2011;Priemel et al, 2013). Such changes induced within the chitospheres by addition of PMMA and its pH-responsive dissolution may significantly prolong drug release.…”