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. 2020 Apr 9;12(4):337.
doi: 10.3390/pharmaceutics12040337.

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion-Preparation of Amorphous Solid Dispersions

Marius Monschke  1 , Kevin Kayser  1 , Karl G Wagner  1
Affiliations

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion-Preparation of Amorphous Solid Dispersions

Marius Monschke et al. Pharmaceutics. .

Abstract

The preparation of amorphous solid dispersions (ASDs) is a suitable approach to overcome solubility-limited absorption of poorly soluble drugs. In particular, pH-dependent soluble polymers have proven to be an excellently suitable carrier material for ASDs. Polyvinyl acetate phthalate (PVAP) is a polymer with a pH-dependent solubility, which is as yet not thoroughly characterized regarding its suitability for a hot-melt extrusion process. The objective of this study was to assess the processability of PVAP within a hot-melt extrusion process with the aim of preparing an ASD. Therefore, the influence of different process parameters (temperature, feed-rate) on the degree of degradation, solid-state and dissolution time of the neat polymer was studied. Subsequently, drug-containing ASDs with indomethacin (IND) and dipyridamole (DPD) were prepared, respectively, and analyzed regarding drug content, solid-state, non-sink dissolution performance and storage stability. PVAP was extrudable in combination with 10% (w/w) PEG 3000 as plasticizer. The dissolution time of PVAP was only slightly influenced by different process parameters. For IND no degradation occurred in combination with PVAP and single phased ASDs could be generated. The dissolution performance of the IND-PVAP ASD at pH 5.5 was superior and at pH 6.8 equivalent compared to commonly used polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and Eudragit L100-55.

Keywords: PVAP; amorphous solid dispersion; dissolution; hot-melt extrusion; polyvinyl acetate phthalate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of polyvinyl acetate phthalate (PVAP) including a possible heat-induced degradation pathway.
Figure 2
Figure 2
Thermogravimetric analysis of neat PVAP, (A) temperature gradient from 25 to 350 °C, (B) isothermal at 120 and 140 °C.
Figure 3
Figure 3
Effect of angular frequency on complex viscosity at different temperatures of the PVAP/PEG 3000 blend (A). Comparison of frequency sweeps of the PVAP/PEG 3000 blend at 120 and 140 °C with copovidone at 150 °C (B).
Figure 4
Figure 4
Residence time distributions at feed-rates of 1, 2 and 3 g/min.
Figure 5
Figure 5
Plot of the sum of free acids against mean residence time (MRT) (A) and specific mechanical energy (SME) (B).
Figure 6
Figure 6
Dissolution times of the placebo extrudates at pH 6.8 (A,B) and at pH 5.5 (C,D).
Figure 7
Figure 7
Solid-state of the drug-containing ASDs. X-ray powder diffraction (XRPD) diffractograms (A). Differential scanning calorimetry (DSC) thermograms (B).
Figure 8
Figure 8
Non-sink dissolution of indomethacin (IND)-PVAP ASDs for different hot-melt extrusion (HME) process conditions at pH 5.5 (A) and pH 6.8 (B).
Figure 9
Figure 9
Non-sink dissolution of the IND-PVAP, - hydroxypropylmethylcellulose acetate succinate (HPMCAS), -L100-55 ASDs at pH 5.5 (A) and pH 6.8 (B).
Figure 10
Figure 10
Non-sink dissolution of IND-PVAP ASDs upon storage at different conditions at pH 5.5 (A) and pH 6.8 (B).
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