Orodispersible films based on amorphous solid dispersions of tetrabenazine

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…Some of the reasons given for excipient selection included reliance on previous reports of the use of similar excipients and their historical applicability in ASDs and oral dosage forms (100–125); the physicochemical properties and functions of the excipient, possible interactions between the compound and the excipient, and the miscibility/immiscibility of the compound and excipient (105–108,111,112,114,126–148); the processability or suitability of the excipient for the preparation method (73,105,119,127,149–152); and the possibility of designing a controlled-release profile and/or pH-dependent release of the compound from the amorphous formulation (99,100,107,123,153–156). An attempt to tailor and customize excipients by modifying the functional groups which could be potentially used in ASD formulations has also been reported (157).…”

“…The duration also varied significantly, with stability studies lasting from 24 h to two years (73,74,81,82,84,86,88,92,93,104,105,109,110,113,115,116,118,120,123,124,126,127,129,130,132,134,135,139,143,146,149,153,158,166,169,172,175,176). While most of the studies did not mention the container used for the physical stability test, a few specified, for example, whether a closed or open container was used (88,92,113,123,132,146). Of these six articles that mentioned whether closed or open container was used, only one specifically reported the type of container used (i.e.…”

“…Of these six articles that mentioned whether closed or open container was used, only one specifically reported the type of container used (i.e. high density polyethylene bottle) in the stability study (132) whereas the remaining studies mentioned only that tube (88), airtight brown vial (92), vial (113), sealed aluminum strip (123) or sealed glass container (146) was used. These large variations in the design of stability studies make direct comparison impossible, since the stability profile obtained is specific only for the stability method employed.…”

“…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.…”

“…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). These disparities in medium used affect the conclusions, which (as with the stability studies) make head-to-head comparison difficult.…”