A review of pharmaceutical extrusion: Critical process parameters and scaling-up

Thiry, Justine; Krier, Fabrice; Évrard, Brigitte

doi:10.1016/j.ijpharm.2014.12.036

Cited by 136 publications

(67 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[25][26][27][28][29][30][31][32][33][34]. In such systems, thermoplastic matrix forming polymers are co-melted/cooled with API(s) in order to prepare several types of solid formulations, including eutectic mixtures, micro-or nano-sized crystalline (or semi-crystalline) solid dispersions or solid solutions (substitutional, interstitial or amorphous) [28,29,[35][36][37][38]. However, despite the large number of studies published on SDs, only a limited number of products have been introduced into the market [35,37,39].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Nanaki¹,

Eleftheriou²,

Barmpalexis³

et al. 2019

Sci

View full text Add to dashboard Cite

In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism.

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Nanaki¹,

Eleftheriou²,

Barmpalexis³

et al. 2019

Sci

View full text Add to dashboard Cite

show abstract

“…The HME process for PVP VA64 containing ASD of compound X was scaled up from 16-to 18-mm extruder using volumetric and power scale up approaches, which have been successfully used by other researchers (37). There were differences in terms of free volume, length/diameter (L/D), and external/internal screw diameter (D o /D i ) ratio between 16-and 18-mm extruders; hence, extrusion process conditions were adjusted to achieve similar specific energy range as shown in Table VI (37).…”

Section: Scale Up Of Hme Process To Clinical Scalementioning

confidence: 99%

“…There were differences in terms of free volume, length/diameter (L/D), and external/internal screw diameter (D o /D i ) ratio between 16-and 18-mm extruders; hence, extrusion process conditions were adjusted to achieve similar specific energy range as shown in Table VI (37). Due to lack of geometric similarities between both extruders, the feed rate for the 18-mm extruder was estimated using volumetric scale-up equation as shown in Table VI (37). The estimated feed rate resulted in similar specific energy values when compared to specific energy of 16-mm extruder batch (Table VI).…”

Section: Scale Up Of Hme Process To Clinical Scalementioning

confidence: 99%

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

2015

View full text Add to dashboard Cite

Abstract. The objective of the study was to develop an amorphous solid dispersion (ASD) for an insoluble compound X by hot melt extrusion (HME) process. The focus was to identify material-sparing approaches to develop bioavailable and stable ASD including scale up of HME process using minimal drug. Mixtures of compound X and polymers with and without surfactants or pH modifiers were evaluated by hot stage microscopy (HSM), polarized light microscopy (PLM), and modulated differential scanning calorimetry (mDSC), which enabled systematic selection of ASD components. Formulation blends of compound X with PVP K12 and PVP VA64 polymers were extruded through a 9-mm twin screw mini-extruder. Physical characterization of extrudates by PLM, XRPD, and mDSC indicated formation of single-phase ASD's. Accelerated stability testing was performed that allowed rapid selection of stable ASD's and suitable packaging configurations. Dissolution testing by a discriminating two-step non-sink dissolution method showed 70-80% drug release from prototype ASD's, which was around twofold higher compared to crystalline tablet formulations. The in vivo pharmacokinetic study in dogs showed that bioavailability from ASD of compound X with PVP VA64 was four times higher compared to crystalline tablet formulations. The HME process was scaled up from lab scale to clinical scale using volumetric scale up approach and scale-independent-specific energy parameter. The present study demonstrated systematic development of ASD dosage form and scale up of HME process to clinical scale using minimal drug (∼500 g), which allowed successful clinical batch manufacture of enabled formulation within 7 months.

show abstract

“…HME presents many advantages, such as the possibility of working without solvents (which is not the case for spray drying), thereby avoiding the need for subsequent drying steps (Bruce et al, 2005). Furthermore, it is a low cost process that allows fast production with a small ecological footprint and the ability to work continuously (Thiry et al, 2015). One common solution for increasing the solubility of a BCS II drug is by converting the crystalline drug into its amorphous form.…”

Section: Introductionmentioning

confidence: 99%

Bioavailability enhancement of itraconazole-based solid dispersions produced by hot melt extrusion in the framework of the Three Rs rule

Thiry

Kok

Collard

et al. 2017

European Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

A review of pharmaceutical extrusion: Critical process parameters and scaling-up

Cited by 136 publications

References 50 publications

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

Bioavailability enhancement of itraconazole-based solid dispersions produced by hot melt extrusion in the framework of the Three Rs rule

Contact Info

Product

Resources

About