Impact of the State of Water on the Dispersion Stability of a Skin Cream Formulation Elucidated by Magnetic Resonance Techniques

Published on Jan 1, 2011in Chemical & Pharmaceutical Bulletin1.405
· DOI :10.1248/cpb.59.332
Masato Nishikawa4
Estimated H-index: 4
(Hoshi University),
Yoshinori Onuki15
Estimated H-index: 15
(Hoshi University)
+ 1 AuthorsKozo Takayama47
Estimated H-index: 47
(Hoshi University)
This study investigated the relationship between the state of water and the dispersion stability of a skin cream formulation. Hydrophilic ointments treated with a high-pressure wet-type jet mill were used as model formulations. Spin–lattice relaxation times (T1) were measured by magnetic resonance techniques to estimate the state of water in samples. A shorter T1 relaxation time was obtained from samples with higher surfactant content, whereas the processing pressure of the jet mill and 1-week storage at 40 °C did not influence the T1 relaxation time. Observations using scanning electron microscopy (SEM) showed that coalescence occurred in samples with lower surfactant contents (1.0% by weight) following 1-week storage at 40 °C. We also investigated samples prepared using a hydrophilic surfactant with a short polyethylene glycol (PEG) chain and with PEG-4000. From the change in T1 relaxation times after removing the oil phase from samples by centrifugation, it was clarified that most of the surfactant was located on the surface of oil droplets. Furthermore, SEM observations showed that phase separation was facilitated as the PEG chain length of the surfactant shortened. Thus, a thin water layer over oil droplets is the most important factor for stabilizing their dispersion. This study provides proof-of-principle results on the contribution of the state of water to the dispersion stability of a skin cream formulation.
  • References (24)
  • Citations (6)
📖 Papers frequently viewed together
63 Citations
6 Citations
8 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Ya Ying Chen (University of Cambridge)H-Index: 1
#2Leslie P. Hughes (AstraZeneca)H-Index: 7
Last. Michael D. Mantle (University of Cambridge)H-Index: 22
view all 4 authors...
ABSTRACT For the first time quantitative Rapid Acquisition with Relaxation Enhancement (RARE) based ultra-fast two-dimensional magnetic resonance imaging has been used to follow the dissolution of hydroxypropylmethyl cellulose (HPMC) in water. Quantitative maps of absolute water concentration, spin-spin relaxation times and water self-diffusion coefficient are obtained at a spatial resolution of 469 mm in less than 3 min each. These maps allow the dynamic development of the medium release rate H...
51 CitationsSource
#1Masato Nishikawa (Hoshi University)H-Index: 4
#2Yoshinori Onuki (Hoshi University)H-Index: 15
Last. Kozo Takayama (Hoshi University)H-Index: 47
view all 4 authors...
Background: A high-pressure wet-type jet mill is a powerful equipment used for the dispersion and emulsification of substances. In this study, we investigated its usefulness in the preparation of skin cream formulations. Method: We prepared a hydrophilic ointment base as a typical skin cream base, and then treated it with the wet-type jet mill under different conditions. Controllable factors of the wet-type jet mill included processing pressure, treatment cycle, and temperature of the treatment....
2 CitationsSource
Abstract Magnetic resonance imaging (MRI) is the technique of choice for measuring hydration, and its effects, during dissolution of tablets since it non-invasively maps 1 H nuclei associated with ‘mobile’ water. Although most studies have used MRI systems with high-field superconducting magnets, low-field laboratory-based instruments based on permanent magnet technology are being developed that provide key data for the formulation scientist. Incorporation of dissolution hardware, in particular ...
66 CitationsSource
#1Isuru N. Seekkuarachchi (University of Toyama)H-Index: 2
#2Kuniaki TanakaH-Index: 3
Last. H. Kumazawa (University of Toyama)H-Index: 11
view all 3 authors...
Abstract A high pressure wet-type jet mill was employed to disperse nano-particle suspensions. Commercially available nano-particles, fumed silica ( SiO 2 ) of primary particle diameter ( d 0 ) ranging from 7 to 40 nm, alumina ( Al 2 O 3 ) of d 0 = 12 nm and titanium oxide ( TiO 2 ) of d 0 = 21 nm were dispersed in the continuous phase up to viscosity η c = 1000 mPa s . Ion exchanged water, aqueous ethylene glycol and aqueous polyethylene glycol solutions with molecular weight up to 2 000 000, w...
23 CitationsSource
#1Ali YilmazH-Index: 4
#2Hatice BudakH-Index: 2
Last. F. Sadan UlakH-Index: 1
view all 3 authors...
The relaxation in protein solutions has mainly been studied by nuclear magnetic relaxation dispersion (NMRD) techniques. NMRD data have mostly been analyzed in terms of fast chemical exchange of water between free water and water bound to proteins. Several approaches were used for the estimation of correlation time modulating the relaxation mechanism of bound water. On the other hand, in a nuclear magnetic resonance experiment, the relaxation rates of protein solutions (1/T1 and 1/T2) and also t...
8 CitationsSource
#1Lazar Fleysher (NYU: New York University)H-Index: 22
#2Roman Fleysher (NYU: New York University)H-Index: 19
Last. Oded Gonen (NYU: New York University)H-Index: 38
view all 5 authors...
Quantitative MR metrics (e.g., T1, T2, diffusion coefficients, and magnetization transfer ratios (MTRs etc)) are often derived from two images collected with one acquisition parameter changed between them (the “two-point” method). Since a low signal-to-noise-ratio (SNR) adversely affects the precision of these metrics, averaging is frequently used, although improvement accrues slowly—in proportion to the square root of imaging time. Fortunately, the relationship between the images' SNRs and the ...
31 CitationsSource
#1I. N. Seekkuarachchi (University of Toyama)H-Index: 2
#2H. Kumazawa (University of Toyama)H-Index: 11
Last. Kuniaki TanakaH-Index: 3
view all 3 authors...
ABSTRACT Emulsions composed of sub-micrometer size droplets were obtained by a high-pressure wet-type jet mill. Liquid paraffin as dispersed phase, aqueous sucrose solution as continuous phase, and anionic sodium dodecyl sulfate as emulsifying agent were used as the model emulsification system. Droplet size distribution, Sauter mean diameter (d 32), geometric standard deviation of the droplet size distribution (σg), and emulsion viscosity (ηe) were investigated under the various combinations of ...
3 CitationsSource
Submicrometer emulsions were generated by a high-pressure wet-type jet mill and a motionless mixer called the Ramond Supermixer. Kerosene and liquid paraffin were used as the dispersed phase, aqueous sucrose and poly(ethylene glycol) solutions of PEG 400 to PEG 20000 were used as the continuous phase, and sodium dodecyl sulfate was used as a surfactant. The droplet size distribution, the Sauter mean diameter (d32), and the geometric standard deviation of the droplet size distribution (σg) were i...
43 CitationsSource
The water mobility and diffusivity in the gel-layer of hydrating low-substituted hydroxypropyl cellulose (LH41) tablets with or without a drug were investigated by magnetic resonance imaging (MRI) and compared with those properties in the gel-layer of hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) tablets. For this purpose, a localized image-analysis method was newly developed, and the spin–spin relaxation time (T2) and apparent self-diffusion coefficient (ADC) of water i...
24 CitationsSource
#1Wilms E. BailleH-Index: 7
#2Cédric MalveauH-Index: 2
Last. Robert H. MarchessaultH-Index: 34
view all 4 authors...
Pharmaceutical tablets made of modified high-amylose starch have a hydrophilic polymer matrix into which water can penetrate with time to form a hydrogel. Nuclear magnetic resonance imaging was used to study the water penetration and the swelling of the matrix of these tablets. The tablets immersed in water were imaged at different time intervals on a 300 MHz NMR spectrometer. Radial images show clearly the swelling of the tablets and the water concentration profile. The rate constants for water...
38 CitationsSource
Cited By6
#1Yoshihisa Yamamoto (Teikyo Heisei University)H-Index: 5
#2Toshiro Fukami (Meiji Pharmaceutical University)H-Index: 13
Last. Tatsuo KoideH-Index: 11
view all 6 authors...
Abstract The purpose of this study is to verify the usefulness of near infrared (NIR) spectroscopy for evaluation of pharmaceutical properties of cream formulations. The present study examined in detail the pharmaceutical properties of clobetasol propionate (CLB) cream formulations using NIR spectroscopy. The characteristic NIR spectrum of Dermovate ® (DRM), the original CLB cream formulation displayed a shoulder around 4800 cm −1 as well as absorption around 5200 cm −1 . A high concentration of...
2 CitationsSource
#1Yoshinori Onuki (University of Toyama)H-Index: 15
#2Masamitsu Yokokawa (Hoshi University)H-Index: 1
Last. Kozo Takayama (Hoshi University)H-Index: 47
view all 8 authors...
: A menthol-diphenhydramine cream is prepared in hospital pharmacies and then prescribed to patients for the treatment of pruritus associated with chronic kidney disease. The purpose of this study is to design a stable formulation without any concern about phase separation during its clinical use on patients. As a preventive measure against phase separation, various surfactants and thickeners were incorporated into the creams. The test creams were stored at 40°C, and then their phase separation ...
1 CitationsSource
#1Yoshinori Onuki (University of Toyama)H-Index: 15
#2Chihiro Kida (Hoshi University)H-Index: 3
Last. Kozo Takayama (Hoshi University)H-Index: 47
view all 5 authors...
We have recently established a novel method to evaluate the emulsion stability of pharmaceutical skin cream. The key technology of the method is magnetic resonance imaging (MRI). The purpose of this study was to verify the usefulness of the method in the cosmetic industry.Milky lotion-type emulsions were employed as test samples. We note that the test samples were prepared by taking account of commercial milky lotions. After the sample preparation, a centrifugation treatment (5000 g for up to 12...
6 CitationsSource
#1Sureewan Duangjit (Ubon Ratchathani University)H-Index: 8
Introduction: In the development of pharmaceutical products, the objective of the formulation optimization is to design and develop the proper dosage form that results in higher efficacy, safety and stability. The formulation efficacy and safety can be assessed during the optimization process. The evaluations for the formulation efficacy and safety saved time more than the formulation stability study. The stability evaluation takes a lot of time for the long term stability study, so several rese...
#1Yoshinori Onuki (Hoshi University)H-Index: 15
#2Naoki Hasegawa (Hoshi University)H-Index: 2
Last. Kozo Takayama (Hoshi University)H-Index: 47
view all 5 authors...
Photocrosslinked polyacrylic acid (PAA–HEMA) hydrogels are a promising candidate for use in dermatological patch adhesives. To gain further knowledge about the properties of this gel, we investigated the T 1 relaxation time and the diffusion coefficient ( D ) of water in the hydrogels using magnetic resonance (MR) imaging. Hydrogels with different formulations and process factors were prepared and tested. The observed data were analyzed by ANOVA, which clarified the mode of action of the formula...
5 CitationsSource
#1Yoshinori Onuki (Hoshi University)H-Index: 15
#2Akihiro HoritaH-Index: 2
Last. Kozo Takayama (Hoshi University)H-Index: 47
view all 6 authors...
AbstractA non-destructive method for monitoring creaming of emulsion-based formulations is in great demand because it allows us to understand fully their instability mechanisms. This study was aimed at demonstrating the usefulness of magnetic resonance (MR) techniques, including MR imaging (MRI) and MR spectroscopy (MRS), for evaluating the physicochemical stability of emulsion-based formulations. Emulsions that are applicable as the base of practical skin creams were used as test samples. Subst...
5 CitationsSource