Effect of the solid-dispersion method on the solubility and crystalline property of tacrolimus

Joe, Jung Hyun; Lee, Won Mo; Park, Young-Joon; Joe, Kwan Hyung; Oh, Dong Hoon; Seo, Youn Gee; Woo, Jong Soo; Yong, Chul Soon; Choi, Han‐Gon

doi:10.1016/j.ijpharm.2010.05.023

Cited by 107 publications

(61 citation statements)

References 27 publications

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“…Numerous technologies have been widely attempted to prepare SDs, such as melting method, solvent-evaporation method and solvent-wetting method (Yamashita et al, 2003;Miller et al, 2007;Joe et al, 2010). However, there are some limitations of using these methods such as the degradation of drug due to the requirement of relatively high preparation temperatures, and the toxicity associated with the use of organic solvents.…”

Section: Introductionmentioning

confidence: 99%

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Xie

Cao

et al. 2014

Drug Delivery

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This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and C max in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

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Section: Introductionmentioning

confidence: 99%

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Xie

Cao

et al. 2014

Drug Delivery

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“…The spray-dried PVP nanosphere formulation was expected to contain the amorphous form of the drug; 22 however, the PXRD pattern showed that only the intensity of the …”

Section: P0mentioning

confidence: 99%

“…18,19 Spray drying is one of the most frequently employed techniques in the preparation of a dry powder from a liquid phase, 20 because of the simple operation, good yield, and the fact that it is easy to scale up. 21,22 In the process of nanoparticle manufacture, all of the components, completely dissolved in suitable solvents, are sprayed into a stream of hot air to evaporate the solvent. 23 A polymeric nanosphere is a nano-sized, round-shaped structure in which the drug is uniformly distributed in the matrix.…”

Section: Introductionmentioning

confidence: 99%

Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

Yousaf¹,

Kim²,

Oh³

et al. 2015

IJN

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Background The intention of this research was to prepare and compare various solubility-enhancing nanoparticulated systems in order to select a nanoparticulated formulation with the most improved oral bioavailability of poorly water-soluble fenofibrate. Methods The most appropriate excipients for different nanoparticulated preparations were selected by determining the drug solubility in 1% (w/v) aqueous solutions of each carrier. The polyvinylpyrrolidone (PVP) nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanocorpuscles, and gelatin nanocapsules were formulated as fenofibrate/PVP/sodium lauryl sulfate (SLS), fenofibrate/HP-β-CD, and fenofibrate/gelatin at the optimized weight ratios of 2.5:4.5:1, 1:4, and 1:8, respectively. The three solid-state products were achieved using the solvent-evaporation method through the spray-drying technique. The physicochemical characterization of these nanoparticles was accomplished by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Their physicochemical properties, aqueous solubility, dissolution rate, and pharmacokinetics in rats were investigated in comparison with the drug powder. Results Among the tested carriers, PVP, HP-β-CD, gelatin, and SLS showed better solubility and were selected as the most appropriate constituents for various nanoparticulated systems. All of the formulations significantly improved the aqueous solubility, dissolution rate, and oral bioavailability of fenofibrate compared to the drug powder. The drug was present in the amorphous form in HP-β-CD nanocorpuscles; however, in other formulations, it existed in the crystalline state with a reduced intensity. The aqueous solubility and dissolution rates of the nanoparticles (after 30 minutes) were not significantly different from one another. Among the nanoparticulated systems tested in this study, the initial dissolution rates (up to 10 minutes) were higher with the PVP nanospheres and HP-β-CD nanocorpuscles; however, neither of them resulted in the highest oral bioavailability. Irrespective of relatively retarded dissolution rate, gelatin nanocapsules showed the highest apparent aqueous solubility and furnished the most improved oral bioavailability of the drug (~5.5-fold), owing to better wetting and diminution in crystallinity. Conclusion Fenofibrate-loaded gelatin nanocapsules prepared using the solvent-evaporation method through the spray-drying technique could be a potential oral pharmaceutical product for administering the poorly water-soluble fenofibrate with an enhanced bioavailability.

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“…Thus, our results suggest that the drug existed in a crystalline and amorphous form in SMSD and SESD, respectively. 31,32 The PXRD profiles shown in Figure 6B were investigated for further verification of the internal physical state of the drug in these formulations. The drug (Figure 6Ba) showed a typical crystalline pattern, but carriers such as HPC (Figure 6Be) and silicon dioxide (Figure 6Bb) showed no peaks.…”

mentioning

confidence: 99%

“…31 The FTIR spectra of ezetimibe, carriers, and the formulations are shown in Figure 6C. The IR spectrum of ezetimibe (Figure 6Ca) was characterized by principal absorption peaks at 3,264.41, 2,913.81, 2,855.57, 1,879.87, 1,718.04, 1,602.50, 1,509.34, 1,445.82, 1,432.02, 1,354.03, 1,221.51, and 830.98 cm -1 .…”

mentioning

confidence: 99%

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

Rashid¹,

Kim²,

Yousaf³

et al. 2015

IJN

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Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility.

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Effect of the solid-dispersion method on the solubility and crystalline property of tacrolimus

Cited by 107 publications

References 27 publications

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

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