A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties

Abstract

The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect.

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets

“…PVP is frequently used in HME to enhance the dissolution pattern of poorly soluble molecules (24)(25)(26)(27)(28). TGA thermographs ( Figs.…”

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). …”

“…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.…”

“…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. 6).…”