Pharmaceutical nanotechnologyDevelopment of a modified – solid dispersion in an uncommon approach of melting method facilitating properties of a swellable polymer to enhance drug dissolution
Graphical abstract
Introduction
Solid dispersion (SD) is a potential approach in enhancing dissolution and bioavailability of poorly water-soluble drugs. Advantages of the technique such as simplicity, economization, and others have been widely reported (Vasconcelos et al., 2007). There are two basic different preparation methods of SD including melting method and solvent evaporation method (Tran et al., 2009, Tran et al., 2010). Melting method was first demonstrated by Sekiguchi and Obi (1961). The product was prepared by melting drug with carrier, then cooling and pulverization. In the melting process, high mobility of carrier would change the combination of drug (van Drooge et al., 2006). In solvent evaporation method, drug and carrier were completely dissolved in a volatile solvent such as ethanol, chloroform, or a mixture of ethanol and dichloromethane (Hasegawa et al., 2005, Lloyd et al., 1999, Rodier et al., 2005) at a low temperature to avoid thermal degradation of drug and carrier (Won et al., 2005). The later method has some disadvantages such as high preparation cost, incomplete solvent removal, alteration in product performance with the change of condition applied (Vasconcelos et al., 2007).
The swellable hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) were introduced in this study to modulate drug release from a SD (Tran et al., 2011, Tran and Tran, 2013). As they are hydrophilic, these polymers may improve the solubility of poorly water-soluble drugs, and their swellable properties may be exploited to promote controlled drug release. The utilization of these two polymer properties in one system might facilitate the development of specialized drug delivery systems by both enhancing drug solubility and controlling the release of poorly water-soluble drugs. This hypothesis was tested herein through the preparation of SDs. However, these polymers are difficult to melt at high temperatures for SD preparation. On the other hand, disadvantages are usually met in the solvent method as mentioned above. Moreover, drugs may be precipitated during solvent removal, leading to the failure of the method intended to enhance drug solubility. Slow drug dissolution rates result when the drugs are not well distributed in the polymer. Therefore, the SD method is not always a successful approach to improve drug solubility. Thus, in this paper, an SD system using the melting method was developed as a new feasible technique using swellable hydrophilic polymers. The system was fabricated not only to increase the dissolution rates of poorly water-soluble drugs, but also to potentially control the release of those drugs. Curcumin (CUR), a poorly water-soluble drug with many potential applications, was used as the model drug in this study. The crystalline behaviors and molecular interactions in the system were investigated to elucidate the potential of this system.
Section snippets
Materials
Curcumin and sodium hydroxide (NaOH) were purchased from Guanghua Sci-Tech Company (China). Hydroxypropyl methyl cellulose (HPMC 4000, HPMC 6) and polyethylene oxide N-60K (PEO) was provided by from Dow Chemical Company (USA). Polyethylene glycol (PEG 6000) was purchased from Sino-Japan Chemical (Taiwan). Methanol (MeOH) was purchased from Fisher Scientific International, Inc. (US). Hydrochloric acid (HCl) and sodium chloride (NaCl) were purchased from Xilong Chemical Industry Incorporated
Dissolution and solubility studies
Our preliminary study showed that CUR was poorly soluble and had lower solubility in acidic medium than basic medium. Specifically, solubility of CUR at pH 1.2 and pH 6.8 were 7.230 ± 0.35 and 12.6 23 ± 3.54, respectively. For this reason, most dissolution release rate of CUR from SDs in the current studies in intestinal fluid (pH 6.8) was faster than that in gastric fluid (pH 1.2) and the percentage of pure CUR released in these media was under 5% in previous studies (Tran et al., 2015).
Conclusion
HPMC 4000 was demonstrated to be an effective swellable polymer in combination with PEG 6000 for enhancing drug dissolution in modified SDs. Method II, in which PEG 6000 and HPMC 4000 were mixed before the drug was dispersed in the polymer mixture, was found to be the best combination method to achieve the aim of the study. This combination method facilitated the swelling of HPMC 4000, resulting in good drug dispersion to change and maintain drug structure to amorphous form but also for
Acknowledgement
We would like to thank International University, Vietnam National University, Ho Chi Minh City (SV2013-01-BME) for partially supporting research grant.
References (25)
- et al.
Effects of water content in physical mixture and heating temperature on crystallinity of troglitazone-PVP K30 solid dispersions prepared by closed melting method
Int. J. Pharm.
(2005) - et al.
Improving drug solubility for oral delivery using solid dispersions
Eur. J. Pharm. Biopharm.
(2000) - et al.
Preparation of chitosan/cellulose acetate blend hollow fibers for adsorptive performance
J. Membr. Sci.
(2005) - et al.
A calorimetric investigation into the interaction between paracetamol and polyethlene glycol 4000 in physical mixes and solid dispersions
Eur. J. Pharm. Biopharm.
(1999) - et al.
Water soluble complexes of curcumin with cyclodextrins: characterization by FT-Raman spectroscopy
Vib. Spectrosc.
(2012) - et al.
A three step supercritical process to improve the dissolution rate of eflucimibe
Eur. J. Pharm. Sci.
(2005) - et al.
Modulation of microenvironmental pH and crystallinity of ionizable telmisartan using alkalizers in solid dispersions for controlled release
J. Control. Release
(2008) - et al.
Investigation of polyethylene oxide–based prolonged release solid dispersion containing isradipine
J. Drug Deliv. Sci. Technol.
(2013) - et al.
The roles of acidifiers in solid dispersions and physical mixtures
Int. J. Pharm.
(2010) - et al.
Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug
Eur. J. Pharm. Biopharm.
(2009)