Dissolution and absorption of nifedipine in polyethylene glycol solid dispersion containing phosphatidylcholine

Law, S. L.; Lo, W. Y.; Lin, Fang-Chi; Chaing, C.H.

doi:10.1016/0378-5173(92)90056-8

Cited by 70 publications

(27 citation statements)

References 9 publications

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“…In this study, the oral administration of the NI-loaded cubosomes (0.5 mg/kg equivalent of NI) gave an AUC 0-∞ value of 58540 ng min/mL, indicating that the formulation of NI with monoolein cubosomes led to a 4-fold increase in the AUC 0-∞ compared with a solid dispersion of NI. 29) Furthermore, the half-lives of the SPI-and NI-loaded cubosomes increased around 1.5-fold compared with the corresponding cubosome-free dispersions. Based on these results, we speculated that several factors could be responsible for the observed increases in the absorption characteristics of these two drugs.…”

Section: Characterization Of Spi-and Ni-loaded Cubosomesmentioning

confidence: 97%

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes

et al. 2017

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Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI-and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, 13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, 12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NIloaded and blank cubosomes existed in the cubic space group Im3 m. The lattice parameters of the SPI-and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI-and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.Key words cubosome; drug carrier; monoolein; nifedipine; spironolactone; high-pressure homogenizationThe low oral bioavailability of poorly water-soluble drugs remains one of the most challenging aspects of drug development. A wide variety of formulation approaches, including lipid nanoparticles, solid dispersions, complexes with cyclodextrin or chitosan-alginates, nanoemulsions and liposomes, have been used to enhance the solubility and bioavailability of several poorly water-soluble drugs. [1][2][3][4][5] Cubosomes have recently attracted considerable interest from formulation scientists in terms of their potential application as drug delivery systems based on their highly ordered, compartmentalized internal structures, high lipid content and large surface area.Cubosomes are inverse bicontinuous cubic lyotropic crystalline nanoparticles that can be loaded with poorly water-soluble drugs in their three-dimensional cubic phases, leading to pronounced increases in the solubility, stability and bioavailability of these drugs.6-9) Cubosomes can be prepared using nontoxic, biocompatible and biodegradable ingredients, and can be readily used to encapsulate lipophilic drugs. Monoolein is a common amphiphilic building block for the preparation of cubosomes, 10) and is relatively cheap compared with other commonly used lipid excipients such as phytantriol. Nonionic triblock copolymer (Pluronic F-127) is ...

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Section: Characterization Of Spi-and Ni-loaded Cubosomesmentioning

confidence: 97%

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes

et al. 2017

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“…Direct filling of hard gelatin capsules with the liquid melt of solid dispersions avoids grinding-induced changes in the crystallinity of the drug. A surfactant must be mixed with the carrier to avoid formation of a drug-rich surface layer (e.g., poly-sorbate80 with PEG, phosphatidyl choline with PEG) 65,66 . The temperature of the molten solution should not exceed ~70-C because it might compromise the hard-gelatin capsule shell.…”

Section: Direct Capsule Fillingmentioning

confidence: 99%

Untitled

2010

IJPSR

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The solubility behavior of drugs remains one of the most challenging aspects in the formulation development. Although there was a great interest in solid dispersion systems during the past four decades to increase solubility by improving dissolution rate and bioavailability of poorly soluble drugs; there commercial use has been very limited, primarily because of manufacturing difficulties and various stability problems. It can be carried out by reducing drug particle size to the absolute minimum, and hence improving drug wet-ability, bioavailability may be significantly improved. Solid dispersion of drugs was generally produced by melt or solvent evaporation methods. Recently, surfactants have been included to stabilize the formulations, thus avoiding drug recrystallization and potentiating their solubility. New manufacturing processes to obtain solid dispersions have also been developed to reduce the drawbacks of the initial process. In this review, it is intended to discuss the eminent approach to improve the solubility or the dissolution rate and recent revival has been discussed.

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“…Most of papers dealing with nifedipine co-precipitate concern a variety of carriers, such as phosphatidylcholine [2] , mannitol [3] , solutol [4] , PEG [5] , poloxamer [6] , sodium starch glycollate, croscarmellose sodium, eudragit E-100 [7] , Gelucire 44/14 [8] , HPMC [9] , Pluronic F68 and Gelucire 50/13 [10] in the form of solid or surface dispersions and co-precipitates [12] . Few examples can be found for nifedipine tested with soluplus, a new attractive carrier [12][13][14][15] to prepare co-precipitate of drug by hot-melt extrusion [16] .…”

Section: Introductionmentioning

confidence: 99%

Release Problems for Nifedipine in the Presence of Soluplus

Fini¹,

Cavallari²,

Ternullo³

et al. 2016

JPP

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Nifedipine/soluplus co-precipitates were prepared at 1:9 and 1:1 weight ratios, using the solvent method, with the aim to obtain an improvement of the drug release. The release, though accelerated with respect to physical mixtures and pure drug, resulted slow with respect to similar systems containing soluplus and are characterized by the appearance in suspension of micro-particulates that, at the optical microscope, revealed a large variety of shapes typical of flower-like aggregates, not previously reported. For comparison systems were also prepared with PVP K30 and sucrester P1670 and two mixtures, without any evidence of this last phenomenon. The systems were studied by thermal (differential scanning calorimetry -DSC, thermomicroscopy -HSM) and spectroscopic (SEM, FT-IR, micro-Raman) analysis. Slow release of nifedipine and formation of colloidal micro-particulates were hypothesized due to the gelling tendency of soluplus associated to drug/polymer multi-site-interactions: when one of these parameters is absent in the system the two phenomena could not be observed together, such as in the case of PVP K30 or sucrester P1670, when used as carriers for nifedipine release.

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Dissolution and absorption of nifedipine in polyethylene glycol solid dispersion containing phosphatidylcholine

Cited by 70 publications

References 9 publications

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes

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Release Problems for Nifedipine in the Presence of Soluplus

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