Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks

Barmpalexis, Panagiotis; Koutsidis, Ioannis A.; Karavas, Evangelos; Louka, Dimitra; Papadimitriou, Sofia; Bikiaris, Dimitrios N.

doi:10.1016/j.ejpb.2013.03.013

Cited by 50 publications

(26 citation statements)

References 35 publications

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“…The SD tablet needed more time to achieve the highest release compared with the corresponding SD, which may be attributed to the slower disintegration of the tablet (Barmpalexis, 2013). The SD-T achieved the highest release at 96.4% in 20 min, which was about 2-fold higher than that of the commercial tablet.…”

Section: The Dissolution Testmentioning

confidence: 92%

“…And there were deviations between the estimated and the measured ones. The negative deviation illustrated that the interactions between the drug and polymer were not strong and it occurred mainly between like molecules and might lead to phase separation, while, if the deviation was positive, this indicated that the drug was miscible with polymer and the interactions contributed to stabilizing the system (Tajber et al, 2005;Zhang, 2009;Barmpalexis, 2013). Figure 6 can be divided into two sections.…”

Section: Prediction Of the Intermolecular Interactionsmentioning

confidence: 99%

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Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

et al. 2014

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The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg. The drug was proved to be miscible with Soluplus by calculation and measurements. The solubility, dissolution, thermal characteristics, interactions and physical stability of the SIM/Soluplus SDs were investigated. The crystal state of simvastatin in the SD was found to change from crystalline to amorphous form during the HME process and also hydrogen bonds were observed between SIM and the extruded Soluplus. The phase solubility showed the solubilization effect of Soluplus was strong and spontaneous. The equilibrium solubility illustrated that Soluplus/SIM SDs gained much higher solubility than its corresponding physical mixtures (PMs). Both of the dissolution profiles and in-vivo performance showed that the SIM/Soluplus SD obtained a marked enhancement, compared with the PM. There was a little change in the SIM/Soluplus SD during a 3-month storage period (40 C, 75%), indicating the good physicochemical stability. The extruded Soluplus system prepared by HME is a good alternative for the water-insoluble SIM to improve the stability and bioavailability.

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Section: The Dissolution Testmentioning

confidence: 92%

Section: Prediction Of the Intermolecular Interactionsmentioning

confidence: 99%

Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

et al. 2014

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“…In all cases, one of the most significant reasons for these observed limitations is the fact that the majority of the published and ongoing research is still handling preliminary proof of concept trials based on binary SD systems In binary SDs an API matrix system is usually developed by dispersing the API on a single thermoplastic matrix forming carrier, which, in most cases, is a polymer or a copolymer. On the contrary, in a more realistic product development scenario ternary (or higher) SDs having instead of the two said components (i.e., an API and a polymer) a third component with multi-functionality (such as matrix forming, plasticizing, crystallization inhibiting and dissolution rate enhancing abilities) are usually needed [40][41][42][43][44][45][46][47][48][49][50]. When designing such multi-component SDs the complexity of formulation development increases by much, since several factors, including the selection of appropriate polymer/additive composition and the synergistic/antagonistic effects of all components, are introduced into the system.…”

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

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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.

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“…This could be attributed to the evolved interactions between CAN and PVP-K30 (Barmpalexis et al, 2013) or glycosidic linkages of naringin, which requires further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation

Surampalli¹,

Nanjwade

Patil

et al. 2014

Drug Delivery

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Objective: The aim of this study was to develop a novel tablet formulation of amorphous candesartan cilexetil (CAN) solid dispersion involving effective P-gp inhibition for optimal drug delivery by direct compression (DC) method. Methods: To accomplish DC, formulation blends were evaluated for micromeritic properties. The Carr index, Hausner ratio, flow rate and cotangent of the angle a were determined. The tablets with and without naringin prepared by DC technique were evaluated for average weight, hardness, disintegration time and friability assessments. The drug release profiles were determined to study the dissolution kinetics. In vivo pharmacokinetic studies were conducted in rabbits. Accelerated stability studies were performed for tablets at 40 ± 2 C/75% RH ± 5% for 6 months. Results: FTIR studies confirmed no discoloration, liquefaction and physical interaction between naringin and drug. The results indicated that tablets prepared from naringin presented a dramatic release (82%) in 30 min with a similarity factor (76.18), which is most likely due to the amorphous nature of drug and the higher micromeritic properties of blends. Our findings noticed 1.7-fold increase in oral bioavailability of tablet prepared from naringin with mean C max and AUC 0-12 h values as 35.81 ± 0.13 mg/mL and 0.14 ± 0.09 mg h/mL, respectively. The tablets with and without naringin prepared by DC technique were physically and chemically stable under accelerated stability conditions upon storage for 6 months. Conclusion: These results are attractive for further development of an oral tablet formulation of CAN through P-gp inhibition using naringin, a natural flavonoid as a pharmaceutical excipient.

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Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks

Cited by 50 publications

References 35 publications

Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

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

Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation

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