Melt extrusion with poorly soluble drugs – An integrated review

The solid‐form screening of active principal ingredients is a challenge for pharmaceutical drug development, as more than 80 % of marketed drugs are formulated in the solid form. A broad and comprehensive study of the various solid forms of drugs is needed to enhance their translation into the clinic. Therefore, the most suitable solid form must be taken into consideration regarding ex vivo and in vivo stability, targeting, solubility, dissolution rate, and bioavailability. In this review, techniques of solid‐form screening are covered, including differences in solid forms such as polymorphs, solvates, salts, co‐crystals, and amorphous particles. Moreover, solid drug size reduction is also discussed, with insight into the emergence of drug nanocrystal formulations. An overview of the smallest nanocrystals reported in the literature and on the market is also provided, along with their applications and routes of administration.

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“…This methode nables mixingo ft he ingredients in an ew solid dispersion amorphousmatrix, after coolingt he system. [40]…”

Section: Solventevaporation Vs Hot-melt Extrusionmentioning

confidence: 99%

State of the Art of Pharmaceutical Solid Forms: from Crystal Property Issues to Nanocrystals Formulation

et al. 2018

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“…Besides spray drying, hot-melt extrusion (HME) is a well-established production technique for ASDs [25,26]. HME can be considered as beneficial compared to spray drying when it comes to the adjustment of the particle size, since tailored downstream processing can easily be applied.…”

Section: Introductionmentioning

confidence: 99%

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

2020

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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.

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“…Hot-melt extrusion (HME) of biodegradable polymers with API, for controlling or modifying the drug release, has received increased attention in the pharmaceutical literature in recent years [6,7]. Compared with other classical preparing techniques, the benefits of HME include being solvent-free, having a high-throughput continuous process, and ease of scaling up [8].…”

Section: Introductionmentioning

confidence: 99%

Clay-Polymer Nanocomposites Prepared by Reactive Melt Extrusion for Sustained Drug Release

Liu¹,

et al. 2020

Pharmaceutics

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Clay–polymer nanocomposites have exhibited a great potential as carriers for controlled release drug delivery. This study aims to prepare exfoliated montmorillonite–Eudragit RS nanocomposites using reactive melt extrusion and investigate the influence of claying loading, clay types (sodium montmorillonite (Cloisite Na) vs. organomodified montmorillonite (Cloisite 20)) on clay–polymer interactions and drug release properties. The clays were used as the filler material at various levels in Eudragit RS and theophylline was used as the active pharmaceutical ingredient. The resulting structure of the nanocomposites was characterized using TEM (transmission electron microscopy) and XRPD (X-ray powder diffraction). The hygroscopicity of the nanocomposites was investigated using DVS (dynamic vapor sorption). The effect of the interfacial interaction between the polymer and clay sheet, the clay loading as well as the clay type on the drug release behavior were further studied by dissolution testing. TEM and XRPD data show that when the clay content is increased from 5% to 15% by weight, the nanocomposite’s structure switches from a fully exfoliated state to intercalated structures or partial exfoliation with stacked clay layers. FT-IR (fourier transform infrared spectroscopy) and ssNMR (solid-state NMR) results suggest that Cloisite Na and Cloisite 20 layers exhibit different interaction strengths with polymer networks by creating compacted complex structures. The addition of nanoclay in the formulation could robustly adjust drug release profiles, and the clay concentration and type are important factors that affect the crossing-linking density of the nanocomposites by adjusting the drug release properties. This study indicates that the clay–Eudragit RS nanocomposites provide an improved oral controlled drug delivery system that minimizes the drug dosing frequency, potentially leading to improved patient compliance.

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Melt extrusion with poorly soluble drugs – An integrated review

Cited by 188 publications

References 158 publications

State of the Art of Pharmaceutical Solid Forms: from Crystal Property Issues to Nanocrystals Formulation

State of the Art of Pharmaceutical Solid Forms: from Crystal Property Issues to Nanocrystals Formulation

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

Clay-Polymer Nanocomposites Prepared by Reactive Melt Extrusion for Sustained Drug Release

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