Pharmaceutical nanotechnologyAmorphous isradipine nanosuspension by the sonoprecipitation method
Graphical abstract
Introduction
Currently, more than 40% of drugs are poorly water-soluble, leading to the poor bioavailability (Müller et al., 2006, Patel and Agrawal, 2011). Therefore, one of the major current challenges of the pharmaceutical industry is related to strategies that improve the water solubility of drugs. A number of studies have been conducted with the aim to enhance solubility and dissolution rate of poorly water-soluble drugs. Sonoprecipitation method is one of the promising approaches for formulation of poorly water-soluble drug compounds (Dalvi and Dave, 2009, Dalvi and Dave, 2010, Dhumal et al., 2008, Liu et al., 2012, Miao et al., 2011, Moorthi and Kathiresan, 2013, Zheng et al., 2010) because ultrasound has been proved to be an effective method for breaking down particles into nanoparticles (Kim et al., 2013). Factors such as amplitude level and ultrasonication time can be controlled to produce highly stable nanosuspension and high drug dissolution rate.
Isradipine (IS), is a dihydropyridine calcium channel blocker, was chosen as the model drug in this research. It is virtually insoluble in water but freely soluble in acetone (Chrysant and Cohen, 1997, Leroueil-Le Verger et al., 1998) and may be degraded under the light. An IS formulation with improvement of dissolution and photo-instability hence should be investigated. In previous studies, we have successfully enhanced the dissolution rate and controlled release rate of IS using solid dispersion techniques (Tran and Tran, 2013, Tran et al., 2010). Recently, Park et al. has developed the inclusion complex of IS and β-cyclodextrin for improvement of photo-instability and dissolution profile (Park et al., 2013). However, there have been few of such studies on nano-sized formulation of IS apart from the research of Verger et al. (Leroueil-Le Verger et al., 1998). The aim of those nanoparticles was to prolong the antihypertensive effect of the drug.
Herein, this study was aimed to develop nanoparticulate systems for improving bioavailability of IS through an improved drug dissolution. Various polymers and ultrasonication conditions were used to investigate the improvement of dissolution rate and nanosuspention stablity. The structural behaviors of drug were characterized by powder X-ray diffraction (PXRD). Morphology and particle size analyses were also conducted through transmission electron microscope (TEM) and scanning electron microscope (SEM). The potential molecular interaction between drug and polymer was also investigated by Fourier transform infrared spectroscopy (FTIR).
Section snippets
Materials
Polyethylene oxide N-60K (PEO), hydroxypropyl methylcellulose 6 cps (HPMC 6) and hydroxypropyl methylcellulose 4000 cps were provided by from Dow Chemical Company (Midland, Michigan, USA). Acetone was purchased from Xilong Chemical Co., Ltd., (Shantou, Guangdong, China). The solvents (methanol and acetonitrile) for high performance liquid chromatography (HPLC) were purchased from Fisher Scientific (Pittsburgh, Pennsylvania, USA). All other chemicals were of analytical grade and were used without
Effect of polymer types and polymer concentrations on dissolution rate of IS
In order to find out the possibility of the varied release rate of drug by polymers, three types of polymers (HPMC 6, HPMC 4000 and PEO) were used to prepare the nanosuspension under the same ultrasonication conditions (Fig. 1). All of the polymers significantly increased the dissolution rate of IS as compared to the dissolution rate of pure drug. Thus, the sonoprecipitation method was effective in enhancing the drug release rate. However, drug release from the nanosuspension of PEO formulation
Conclusion
The sonoprecipitation method showed that it was an effective method for preparation of stable nanosuspension of IS. HPMC 6 significantly increased the dissolution rate of IS. The reduction of drug particle size and the change of crystalline form to amorphous form may attribute the main mechanism to the dissolution enhancement. The stability and size of nanosuspension were significantly affected by ultrasonication conditions such as amplitude level and time. F6 (amplitude level 5 in 5 min) was an
Acknowledgement
This research is funded by the International University, VNU-HCM under grant number SV-06-2012/HĐ-ĐHQT-QHQT&QLKH.
References (23)
- et al.
Long-term antihypertensive effects with chronic administration of isradipine controlled release
Curr. Ther. Res.
(1997) - et al.
Analysis of nucleation kinetics of poorly water-soluble drugs in presence of ultrasound and hydroxypropyl methyl cellulose during antisolvent precipitation
Int. J. Pharm.
(2010) - et al.
Preparation of amorphous cefuroxime axetil nanoparticles by sonoprecipitation for enhancement of bioavailability
Eur. J. Pharm. Biopharm.
(2008) - et al.
Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems
Eur. J. Pharm. Sci.
(2003) - et al.
Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension
Int. J. Pharm.
(2010) - et al.
Effect of ultrasonic treatments on nanoparticle preparation of acid-hydrolyzed waxy maize starch
Carbohydr. Polym.
(2013) - et al.
Preparation and characterization of nanoparticles containing an antihypertensive agent
Eur. J. Pharm. Biopharm.
(1998) - et al.
Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN®) versus drug nanocrystals
Int. J. Pharm.
(2006) - et al.
Fabrication of highly stable sonication assisted curcumin nanocrystals by nanoprecipitation method
Drug Invent. Today
(2013) - et al.
Investigation of polyethylene oxide-based prolonged release solid dispersion containing isradipine
J. Drug Deliv. Sci. Technol.
(2013)
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