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

Thiry, Justine; Kok, Miranda; Collard, Laurence; Frère, Antoine; Krier, Fabrice; Fillet, Marianne; Évrard, Brigitte

doi:10.1016/j.ejps.2016.12.001

Cited by 51 publications

(21 citation statements)

References 36 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dissolution profiles found in this study are very similar to that for the marketed drug Sporanox ® (capsules contain a solid solution of ITZ and hypromellose that is coated on sugar beads produced by Janssen, Belgium). Also, to other formulations containing ITZ and Soluplus ® prepared by Thiry and co-workers, however, it is worth mentioning that the extrudates were not milled (Thiry et al, 2017). Zhong and co-authors indicated that dissolution of Sporanox ® and other ITZ/Soluplus ® formulations prepared by HME can reach up to 80% in 60 min at pH 1.2 (Zhong et al, 2016).…”

Section: In-vitro Dissolutionmentioning

confidence: 99%

“…It has very low aqueous solubility, approximately 1 ng/mL at pH 7 and 4 µg/mL at pH 1 (Peeters et al, 2002), it is highly lipophilic (cLogP 6.2) and weakly basic (pKa values 2 and 4) but demonstrates excellent biological membrane permeability (Brouwers et al, 2017). Separate studies have attempted to increase the bioavailability of ITZ by using spray drying (Kumar et al, 2014), hot melt extrusion (HME) (Janssens et al, 2008;Thiry et al, 2017;Verreck et al, 2003), and crystalline ITZ nanoparticles (Yang et al, 2010b). A previous study by our group showed that combinations of HPMCP and Soluplus ® have a significant effect on the stability of spray dried ITZ against recrystallization (Davis et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion

Albadarin

Potter

Davis

et al. 2017

International Journal of Pharmaceutics

View full text Add to dashboard Cite

The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20°C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (T), around 96.4°C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus. The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ.

show abstract

Section: In-vitro Dissolutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion

Albadarin

Potter

Davis

et al. 2017

International Journal of Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Of note, it has been widely used as a main matrix for the production of HME formulations due to its thermodynamic properties [14,15]. Conclusively, the use of SP in HME processing can improve solubility and the bioavailability of poorly water-soluble drugs [9,14,16,17]. So far, the HME technique has been used principally to make solid dispersions of organic molecules, which have low molecular weight and poor water solubility, with appropriate polymers (i.e., cellulose derivatives, poly (ethylene-co-vinyl acetate), polyethylene glycol, polyvinylpyrrolidone, and SP) [9,14,16,18].…”

Section: Introductionmentioning

confidence: 99%

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

et al. 2017

View full text Add to dashboard Cite

Zinc sulfate monohydrate (ZnSO 4 )-loaded nanocomposites (NCs) were fabricated by using a hot-melt extruder (HME) system. Soluplus (SP) was adopted as an amphiphilic polymer matrix for HME processing. The micro-size of ZnSO 4 dispersion was reduced to nano-size by HME processing with the use of SP. ZnSO 4 could be homogeneously dispersed in SP through HME processing. ZnSO 4 /SP NCs with a 75 nm mean diameter, a 0.1 polydispersity index, and a −1 mV zeta potential value were prepared. The physicochemical properties of ZnSO 4 /SP NCs and the existence of SP in ZnSO 4 /SP NCs were further investigated by solid-state studies. Nano-size range of ZnSO 4 /SP NC dispersion was maintained in the simulated gastrointestinal environments (pH 1.2 and 6.8 media). No severe toxicity in intestinal epithelium after oral administration of ZnSO 4 /SP NCs (at 100 mg/kg dose of ZnSO 4 , single dosing) was observed in rats. These results imply that developed ZnSO 4 /SP NC can be used as a promising nano-sized zinc supplement formulation. In addition, developed HME technology can be widely applied to fabricate nanoformulations of inorganic materials.

show abstract

“…Then, the virtual cocrystal screening was performed for four drugs, namely Iloperidone, Ritonavir, Carbamazepine, Ethenzamide. All these compounds belonging to the II class of Biopharmaceutics Classification System (high permeability and low solubility) have been extensively studied in terms of bioavailability and dissolution profile improvement (Aitipamula et al, 2012;Danjo, K., Nataka, T. & Otsuka, 1997;Foglio Bonda et al, 2016;Gadade et al, 2017;Ibrahim et al, 2010;Ige et al, 2015;Jitkar et al, 2016;Kojo et al, 2017;Miwa et al, 2016;Remenar et al, 2003;Six et al, 2004;Thiry et al, 2017aThiry et al, , 2016. It is understandable that not all pharmaceutically accepted excipients are miscible in the solid phase with a particular API in the form of a cocrystal.…”

Section: Resultsmentioning

confidence: 99%

“…This is in accord with chemical intuition and pharmaceutical drug delivery strategies (Brough et al, 2015;Ghanbarzadeh et al, 2016;Kalepu and Nekkanti, 2015;Maggi et al, 2013;Sareen et al, 2012;Savjani et al, 2012;Serajuddin, 1999;Sruti et al, 2013) that differences in polarities between drug and excipient is a main driving force toward dissolution. Many examples of such cases can be found in the literature, including cocrystals but also other types of solid mixtures such as inclusion complexes with cyclodextrins (Dua et al, 2011;M Badr-Eldin et al, 2013;Thiry et al, 2017aThiry et al, , 2017b and dispersions with soluble polymers (Brough et al, 2015;Choi and Park, 2017;Ibrahim et al, 2010;Maggi et al, 2013;Six et al, 2004;Thiry et al, 2017a). Noteworthy, Guha et al, (2011), found that APIs can be classified in terms of their kinetic solubility values using different hydrophilicity indices.…”

Section: Selection Of Appropriate Molecular Descriptormentioning

confidence: 99%

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Cysewski

Przybyłek

2017

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions H<-0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.

show abstract

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

Cited by 51 publications

References 36 publications

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

Contact Info

Product

Resources

About