Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug

Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

doi:10.1016/j.ijpharm.2013.04.050

Cited by 17 publications

(17 citation statements)

References 5 publications

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“…The bioavailability of granules was 3.7-fold greater than those of NIF powder. Funakoshi et al reported an oral bioavailability of NIF solution of 46.0±6.6 (%), 28) very similar to the value for granules. The in vivo and in vitro results presented here clearly indicate the usefulness of formulating NIF with PCS using wet granulation.…”

Section: Effects Of Amount Of Binder and Pcs On Tablet Propertiessupporting

confidence: 57%

“…Hydrogen bonding between N-H groups of NIF and a water-soluble carrier, such as PVP and HPMC, have been reported. 12,27) In addition, Sharma et al and Kinoshita et al reported hydrogen bonding between the silanol group of PCS and C=O groups of the drug, 14,15) suggesting that decreased crystallinity of NIF might be associated with hydrogen bonding between the C=O/NH groups of NIF and the silanol group of PCS.…”

Section: Effects Of Amount Of Binder and Pcs On Tablet Propertiesmentioning

confidence: 99%

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Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate

Fujimoto

Hirai

Takatani‐Nakase

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The aim of this study was to prepare and evaluate solid dispersion tablets containing a poorly water-soluble drug using porous calcium silicate (PCS) by a wet granulation method. Nifedipine (NIF) was used as the model poorly water-soluble drug. Solid dispersion tablets were prepared with the wet granulation method using ethanol and water by a high-speed mixer granulator. The binder and disintegrant were selected from 7 and 4 candidates, respectively. The dissolution test was conducted using the JP 16 paddle method. The oral absorption of NIF was studied in fasted rats. Xylitol and crospovidone were selected as the binder and disintegrant, respectively. The dissolution rates of NIF from solid dispersion formulations were markedly enhanced compared with NIF powder and physical mixtures. Powder X-ray diffraction (PXRD) confirmed the reduced crystallinity of NIF in the solid dispersion formulations. Fourier transform infrared (FT-IR) showed the physical interaction between NIF and PCS in the solid dispersion formulations. NIF is present in an amorphous state in granules prepared by the wet granulation method using water. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of NIF after dosing rats with the solid dispersion granules were significantly greater than those after dosing with NIF powder. The solid dispersion formulations of NIF prepared with PCS using the wet granulation method exhibited accelerated dissolution rates and superior oral bioavailability. This method is very simple, and may be applicable to the development of other poorly water-soluble drugs.

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Section: Effects Of Amount Of Binder and Pcs On Tablet Propertiessupporting

confidence: 57%

Section: Effects Of Amount Of Binder and Pcs On Tablet Propertiesmentioning

confidence: 99%

Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate

Fujimoto

Hirai

Takatani‐Nakase

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…This also indicates that, under ambient conditions, the shelf life of nifedipine loaded solid-lipid nanoparticles may be increased by more than 6 months, although further study is needed. In addition, our recent study demonstrated that nifedipine solidlipid nanoparticles just after preparation showed improved oral absorption rate in comparison to nifedipine itself 33) ; further in vivo pharmacokinetic study using lyophilized nifedipine solid-lipid nanoparticles with trehalose should also be conducted. In conclusion, nifedipine solid-lipid nanoparticles lyophilized with trehalose might provide effective drug delivery of nifedipine for the treatment of hypertension and angina pectoris.…”

Section: Resultsmentioning

confidence: 96%

Development of Highly Stable Nifedipine Solid–Lipid Nanoparticles

Barman

Iwao

Funakoshi

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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To improve the solubility of the drug nifedipine (NI), highly stabilized solid-lipid nanoparticles (SLNs) of nifedipine (NI-SLNs) were prepared by high pressure homogenization using two phospholipids, followed by lyophilization with individual sugar moieties (four monosaccharides and four disaccharides). The mean particle diameter, polydispersity index (PDI), zeta potential, drug loading, and the encapsulation efficiency of the NI-SLN suspension were determined to be 68.5 nm, 0.3, 62.1 mV, 2.7%, and 97.5%, respectively. In comparison with the NI-SLNs, the NI-SLNs lyophilized with trehalose (NI-SLN-Tre) showed a slight increase in the particle size from 68.5 to 107.7 nm, but the PDI decreased from 0.38 to 0.33, and no significant change in zeta potential was observed. Aqueous re-dispersibility study demonstrated that NI-SLNs lyophilized with trehalose had the maximum concentration (14.7 µg/mL) at 5 min, compared with lyophilized SLNs using other sugars; the use of other sugars also resulted in significant changes in the particle size, PDI, and zeta potential. A trehalose concentration of 2.5% w/v and a two-fold dilution of the SLN suspension were found to be the best conditions for lyophilization. Data from lyophilized SLNs using differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy indicated eventual transformation of NI-SLN-Tre from a crystalline to an amorphous state during the homogenization process. Finally, a stability study was performed with NI-SLN-Tre for up to 6 months at 30°C and 65% relative humidity, with no significant deterioration observed, suggesting that trehalose might be a useful cryoprotectant for NI-SLNs.

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“…4) The LNs improved the solubility of nifedipine (NI), a poorly water-soluble drug, and improved its oral absorption of NI when NI-LNs were administrated to rats. 5) NI-LNs showed excellent long-term stability in suspension for approximately 4 months in cool and dark conditions, and freeze-drying techniques combined with sugar as a cryoprotectant allowed the preparation of LNs with a good aqueous re-dispersibility. 6,7) NI-LNs lyophilized with trehalose exhibited suitable pharmacokinetic properties and good biocompatibility.…”

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confidence: 99%

Effect of Alkyl Chain Length and Unsaturation of the Phospholipid on the Physicochemical Properties of Lipid Nanoparticles

et al. 2015

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Previously, we developed lipid nanoparticles (LNs) containing poorly water-soluble drugs using two types of phospholipids, a neutral phospholipid (hydrogenated soybean phosphatidylcholine) and a negativelycharged phospholipid (dipalmitoylphosphatidylglycerol), with mean particle sizes of less than 100 nm. Here, we studied the effects of alkyl chain length and unsaturation of neutral and negatively-charged phospholipids on the physicochemical properties of LNs. Three neutral phospholipids, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine, having different alkyl chain lengths, were compared. The mean particle size of the LNs increased with the alkyl chain length, while the concentration of the drug entrapped in the LNs decreased. The particle size of all of the LNs could be maintained at less than 100 nm for 1 month in cool and dark conditions, with the LNs with longer alkyl chain lipids showing greater stability. In the unsaturated phospholipids, the double bond in the alkyl chain of dioleoylphosphatidylcholine and dierucoylphosphatidylcholine did not affect the physicochemical properties of the LNs. The negatively-charged phospholipids dipalmitoylphosphatidylglycerol and distearoylphosphatidylglycerol were also compared; LNs with longer alkyl chain lipids had larger particle sizes and lower drug concentrations, similar to the results for neutral phospholipids. We concluded that although some changes in physicochemical properties were observed among LNs with different phospholipid alkyl chain lengths, this methodology was general. LNs with suitable physicochemical properties could be prepared irrespective of the type of phospholipids used.Key words lipid nanoparticle; poorly water-soluble drug; phospholipid; alkyl chain Many candidate active pharmaceutical ingredients (APIs) in formulations show poor solubility in water. To enhance the solubility of such poorly water-soluble APIs, the use of nanoparticle formulations with particle sizes less than 100 nm has recently attracted considerable attention in the field of pharmaceutical research.1-3) Recently, we successfully prepared lipid nanoparticles (LNs), which had a mean particle size of approximately 50 nm with a narrow particle size distribution, using wet milling, roll mixing, and high pressure homogenization to form small particles.4) The LNs improved the solubility of nifedipine (NI), a poorly water-soluble drug, and improved its oral absorption of NI when NI-LNs were administrated to rats. 5) NI-LNs showed excellent long-term stability in suspension for approximately 4 months in cool and dark conditions, and freeze-drying techniques combined with sugar as a cryoprotectant allowed the preparation of LNs with a good aqueous re-dispersibility.6,7) NI-LNs lyophilized with trehalose exhibited suitable pharmacokinetic properties and good biocompatibility. 8) Generally, two types of phospholipids, neutral phosphatidylcholine (PC) and negatively-charged phosphatidylglycerol (PG) are used to prepare LNs. PG was added to...

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Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug

Cited by 17 publications

References 5 publications

Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate

Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate

Development of Highly Stable Nifedipine Solid–Lipid Nanoparticles

Effect of Alkyl Chain Length and Unsaturation of the Phospholipid on the Physicochemical Properties of Lipid Nanoparticles

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