Preparation of carbamazepine–Soluplus® solid dispersions by hot-melt extrusion, and prediction of drug–polymer miscibility by thermodynamic model fitting

Djuriš, Jelena; Nikolakakis, Ioannis; Ibrić, Svetlana; Djurić, Z.; Kachrimanis, Kyriakos

doi:10.1016/j.ejpb.2012.12.018

Cited by 165 publications

(121 citation statements)

References 26 publications

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“…Preparing of CBZ-VA64 and CBZ-Soluplus amorphous solid dispersions by HME has also been reported previously in literature (37). In contrast to our result, Djuris et al reported immiscibility between Soluplus and carbamazepine at 30% drug load (38). However, that study was performed on a melt-fusion product instead of an HME product.…”

Section: Discussioncontrasting

confidence: 54%

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME

Huang

O’Donnell

Keen³

et al. 2015

AAPS PharmSciTech

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Abstract. Hypromellose is a hydrophilic polymer widely used in immediate-and modified-release oral pharmaceutical dosage forms. However, currently available grades of hypromellose are difficult, if not impossible, to process by hot melt extrusion (HME) because of their high glass transition temperature, high melt viscosity, and low degradation temperature. To overcome these challenges, a modified grade of hypromellose, AFFINISOL™ HPMC HME, was recently introduced. It has a significantly lower glass transition temperature and melt viscosity as compared to other available grades of hypromellose. The objective of this paper is to assess the extrudability and performance of AFFINISOL™ HPMC HME (100LV and 4M) as compared to other widely used polymers in HME, including HPMC 2910 100cP (the currently available hypromellose), Soluplus®, Kollidon® VA 64, and EUDRAGIT® E PO. Formulations containing polymer and carbamazepine (CBZ) were extruded on a co-rotating 16-mm twin-screw extruder, and the effect of temperature, screw speed, and feed rate was investigated. The performance of the solid dispersions was evaluated based on Flory-Huggins modeling and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and dissolution. All formulations extruded well except for HPMC 2910 100cP, which resulted in over-torqueing the extruder (machine overloading because the motor cannot provide efficient energy to rotate the shaft). Among the HME extrudates, only the EUDRAGIT® E PO formulation was crystalline as confirmed by DSC, XRD, and Raman, which agreed with predictions from Flory-Huggins modeling. Dissolution testing was conducted under both sink and non-sink conditions. Sink dissolution testing in neutral media revealed that amorphous CBZ in the HME extrudates completely dissolved within 15 min, which was much more rapid than the time for complete dissolution of bulk CBZ (60 min) and EUDRAGIT® E PO solid dispersion (more than 6 h). Non-sink dissolution in acidic media testing revealed that only CBZ contained in the AFFINISOL™ HPMC HME, and EUDRAGIT® E PO solid dispersions rapidly supersaturated after 15 min, reaching a twofold drug concentration compared to the CBZ equilibrium solubility. In summary, AFFINISOL™ HPMC HME 100LV and AFFINISOL™ HPMC HME 4M are useful in the pharmaceutical HME process to increase wetting and dissolution properties of poorly water-soluble drugs like CBZ.

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Section: Discussioncontrasting

confidence: 54%

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME

Huang

O’Donnell

Keen³

et al. 2015

AAPS PharmSciTech

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“…Still, Soluplus® has been shown to enhance solubility to a greater extent for certain APIs relative to other hydrophilic polymers (97). The utility of Soluplus® as a matrix polymer and solubility enhancer in melt-extruded ASDs has been demonstrated for multiple poorly water-soluble drugs, including carbamazepine (95,96,98), fenofibrate (99), simvastatin (100), dronedarone hydrochloride (101), and valsartan (102).…”

Section: Designer Polymers For Extrusion Processingmentioning

confidence: 99%

“…4. The polymer was designed to be both a matrix former and a solubilizer due to its amphiphilic structure (95). It was also designed to be self-plasticizing with a relatively low T g of 70°C to enable extrusion at low temperatures; however, others have shown that Soluplus® still exhibits high complex viscosity above T g and needs to be processed at temperatures as high as 140°C (96).…”

Section: Designer Polymers For Extrusion Processingmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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“…Characteristic IR peaks for crystalline atorvastatin calcium were observed at 3362 cm , and 1631 cm −1 (C= O stretching). 18,19) FT-IR spectra of a physical mixture of atorvastatin calcium and Soluplus ® at a 2 : 8 ratio correspond to a summation of crystalline atorvastatin calcium and Soluplus ® spectra, suggesting that no interactions between the two species or disruption of drug crystallinity occur in the mixtures. Notably, however, the spectra of solid dispersions lack peaks characteristics of crystalline atorvastatin calcium and showed peaks representative of Soluplus ® and amorphous atorvastatin calcium.…”

Section: Characterization and Solubility Of Solid Dispersionsmentioning

confidence: 99%

Preparation and Evaluation of Solid Dispersion of Atorvastatin Calcium with Soluplus® by Spray Drying Technique

Baek

Cho

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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The aim of the present study was to investigate the effect of Soluplus ® on the solubility of atorvastatin calcium and to develop a solid dispersion formulation that can improve the oral bioavailability of atorvastatin calcium. We demonstrated that Soluplus ® increases the aqueous solubility of atorvastatin calcium. Several solid dispersion formulations of atorvastatin calcium with Soluplus ® were prepared at various drug : carrier ratios by spray drying. Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in each solid dispersion, and the 2 : 8 drug : carrier ratio provided the highest degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in rats revealed that the 2 : 8 dispersion significantly improved the oral bioavailability of atorvastatin. This study demonstrates that spray-dried Soluplus ® solid dispersions can be an effective method for achieving higher atorvastatin plasma levels.

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Preparation of carbamazepine–Soluplus® solid dispersions by hot-melt extrusion, and prediction of drug–polymer miscibility by thermodynamic model fitting

Cited by 165 publications

References 26 publications

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Preparation and Evaluation of Solid Dispersion of Atorvastatin Calcium with Soluplus® by Spray Drying Technique

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