Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs

Sarode, Ashish L.; Wang, Peng; Obara, Sakaé; Worthen, David R.

doi:10.1016/j.ejpb.2013.10.005

Cited by 93 publications

(46 citation statements)

References 30 publications

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“…The absence of the typical peak in SIM/Soluplus SD indicated that simvastatin was amorphous in the extruded Soluplus, implying that the morphology of SIM changed during the hot melt extrusion process (Hu et al, 2006;Sarode, 2013). However, in the corresponding PM, the endothermic peak was still observed, though it became much weaker.…”

Section: Differential Scanning Calorimetrymentioning

confidence: 93%

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: Differential Scanning Calorimetrymentioning

confidence: 93%

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

et al. 2014

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“…Several publications on biphasic tests have demonstrated a flexibility to accommodate different kinds of dosage forms, discriminative capability on formulations of poorly soluble drugs and a good potential of achieving an in vitroin vivo relationship. [3][4][5][6][7][8][9] Preliminary modeling of the drug transport in such biphasic systems proposed a theoretical foundation for physiological relevance of the test. 5 This analysis indicated that the apparent partition rate (kp) from the biphasic test could be comparable with the absorption rate (ka) in vivo provided that the experimental scaling factors (e.g., interfacial surface A and aqueous volume V) and the apparent partition coefficient (Pi) of the compound are appropriate.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6][7][8][9] The dissolution-partition system referred as the biphasic test, in this article, contains both aqueous and organic phases and may offer major advantages over single aqueous phase biorelevant dissolution tests. The biphasic test is designed to evaluate dissolution and precipitation of the drug formulations in a biorelevant aqueous phase (under nonsink condition) accompanied by simultaneous partition of the drug from the aqueous phase into the organic phase (under sink condition).…”

Section: Introductionmentioning

confidence: 99%

Assessing Supersaturation and Its Impact on In Vivo Bioavailability of a Low-Solubility Compound ABT-072 With a Dual pH, Two-Phase Dissolution Method

Shi

Erickson

Jayasankar

et al. 2016

Journal of Pharmaceutical Sciences

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ABT-072 is a candidate drug evaluated for treatment of hepatitis C virus. It is an acidic compound with extremely low intrinsic aqueous solubility. An in vitro dissolution-partition system, referred as biphasic test method, was used to characterize ABT-072 prototype formulations. This test used 2 aqueous dissolution media of pH 2 and 6.5 in a sequential manner to simulate the transition of drug in gastrointestinal tract. The biphasic test used in this work effectively differentiated various ABT-072 formulations derived from conventional and enabling technologies. In vitro profiles of these formulations indicate a complex interplay among the 3 competitive kinetic processes including dissolution, precipitation, and partition in the aqueous media. The relative amount of drug partitioned into the organic phase (i.e., octanol) from different formulations was found to be directly related to their in vivo exposures observed in both dogs and human subjects, respectively. An in vitro-in vivo relationship was obtained between ABT-072 concentrations in octanol at t = 2 h from these formulations and the relative bioavailabilities in dogs and human subjects. This work revealed the significance of polymeric precipitation inhibition by sustaining a supersaturated state of ABT-072 and its impact on in vivo exposure in human subjects.

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“…Methods that are available to eliminate the solubility problem (Fahr and Liu, 2007;Sarode et al, 2014) are either costly or their industrial applicability is limited .…”

Section: Introductionmentioning

confidence: 99%

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions

Sóti

Bocz

Pataki

et al. 2015

International Journal of Pharmaceutics

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Three solvent based methods: spray drying (SD), electrospinning (ES) and air-assisted electrospinning (electroblowing; EB) were used to prepare solid dispersions of itraconazole and Eudragit E. Samples with the same API/polymer ratios were prepared in order to make the three technologies comparable. The structure and morphology of solid dispersions were identified by scanning electron microscopy and solid phase analytical methods such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman chemical mapping. Moreover, the residual organic solvents of the solid products were determined by static headspace-gas chromatography/mass spectroscopy measurements and the wettability of samples was characterized by contact angle measurement. The pharmaceutical performance of the three dispersion type, evaluated by dissolution tests, proved to be very similar. According to XRPD and DSC analyses, made after the production, all the solid dispersions were free of any API crystal clusters but about 10 wt% drug crystallinity was observed after three months of storage in the case of the SD samples in contrast to the samples produced by ES and EB in which the polymer matrix preserved the API in amorphous state.

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Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: Polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs

Cited by 93 publications

References 30 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

Assessing Supersaturation and Its Impact on In Vivo Bioavailability of a Low-Solubility Compound ABT-072 With a Dual pH, Two-Phase Dissolution Method

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions

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