Effects of Polymer/Surfactant as Carriers on the Solubility and Dissolution of Fenofibrate Solid Dispersion
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The purpose of this work is to investigate the effects of polymer/surfactant as carriers on the solubility and dissolution of fenofibrate solid dispersions (FF SDs) with the aid of systematic research on the physicochemical properties of the polymer/surfactant system and further highlight the importance of studying polymer/surfactant interaction in the preformulation. The critical micelle concentration (CMC) of sodium lauryl sulfate (SLS) and critical aggregation concentration (CAC) of polymer/SLS solutions were obtained through conductivity measurement. Meanwhile, surface tension, viscosity, morphology, and wettability of polymer/SLS with different weight ratios of SLS were analyzed to screen out the suitable content of SLS (weight%, 5% in carriers) incorporated in SDs. Polymer/SLS coprecipitate and FF SDs were prepared by the solvent evaporation method. The results from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis showed that FF was molecularly dispersed in SDs. Compared to the solubility of FF in povidone/SLS (PVP/SLS) solutions, the increment of FF solubility in copovidone/SLS (VA64/SLS) solutions was due to the formation of free SLS micelles, which have been confirmed by transmission electron microscopy (TEM). Particularly, the wettability of FF SDs and physical mixtures (PMs) was also determined by the sessile drop technique. A linear relationship between the wettability of carriers and that of FF SDs was found, which revealed the significant role of carriers on the surface composition of FF SDs. As the molecular weight of PVP increased, the wettability of carriers decreased, thus leading to the reduction of the dissolution rate of SDs. Although the presence of SLS did not enhance the dissolution of FF SDs, it increased the amount of drug released at the initial stage. All these results indicated that the polymer/SLS interaction would affect the performance of SDs; hence, it was necessary to study their properties in the preformulation.
KEY WORDSpolymer/surfactant interaction solubility dissolution solid dispersion
This work was financially supported by the National Natural Science Foundation of China (No.81473161) and National Science and Technology Major Project (No. 2017ZX09101001-006-012).
Compliance with Ethical Standards
Conflict of Interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
- 1.Bhardwaj V, Trasi NS, Zemlyanov DY, Taylor LS. Surface area normalized dissolution to study differences in itraconazole-copovidone solid dispersions prepared by spray-drying and hot melt extrusion. Int J Pharm. Elsevier; 2018;540:106–19. Available from: https://doi.org/10.1016/j.ijpharm.2018.02.005
- 8.Ng CL, Lee SE, Lee JK, Kim TH, Jang WS, Choi JS, et al. Solubilization and formulation of chrysosplenol C in solid dispersion with hydrophilic carriers. Int J Pharm. Elsevier B.V.; 2016;512:314–21. Available from: https://doi.org/10.1016/j.ijpharm.2016.08.062
- 10.Narang AS, Panakanti R. Impact of excipient interactions on drug bioavailability from solid dosage forms. Excip Appl Formul Des Drug Deliv. 2015:273–310.Google Scholar
- 13.Chiappisi L, Gradzielski M. Co-assembly in chitosan-surfactant mixtures: thermodynamics, structures, interfacial properties and applications. Adv Colloid Interface Sci. Elsevier B.V.; 2015;220:92–107. Available from: https://doi.org/10.1016/j.cis.2015.03.003
- 14.Katona J, Njaradi S, Sovilj V, Petrovic L, Marceta B, Milanovic J. Rheological properties of hydroxypropylmethyl cellulose/sodium dodecylsulfate mixtures. J Serbian Chem Soc. 2014;79:457–68 Available from: http://www.doiserbia.nb.rs/Article.aspx?ID=0352-51391300132K.CrossRefGoogle Scholar
- 15.Prasad M, Palepu R, Moulik SP. Interaction between sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP) investigated with forward and reverse component addition protocols employing tensiometric, conductometric, microcalorimetric, electrokinetic, and DLS techniques. Colloid Polym Sci. 2006;284:871–8.CrossRefGoogle Scholar
- 21.Shi Y, Luo HQ, Li NB. Determination of the critical premicelle concentration, first critical micelle concentration and second critical micelle concentration of surfactants by resonance Rayleigh scattering method without any probe. Spectrochim Acta - Part A Mol Biomol Spectrosc. Elsevier B.V.; 2011;78:1403–7. Available from: https://doi.org/10.1016/j.saa.2011.01.018
- 25.Yang H, Ye H, Zhai S, Wang G. Effect of polymer–surfactant structure on its solution viscosity. Int Symp Adv Control Ind Process. 2011;2011:258–61.Google Scholar
- 27.Affandi MMRMM, Tripathy M, Majeed ABA. Solubility enhancement of simvastatin and atorvastatin by arginine: contact angle determination, wettability and surface energy characteristics. J Mol Liq. Elsevier B.V.; 2017;240:340–4. Available from: https://doi.org/10.1016/j.molliq.2017.05.068
- 30.França MT, Nicolay RP, Klüppel Riekes M, Munari Oliveira Pinto J, Stulzer HK. Investigation of novel supersaturating drug delivery systems of chlorthalidone: the use of polymer-surfactant complex as an effective carrier in solid dispersions. Eur J Pharm Sci Elsevier. 2018;111:142–52.CrossRefGoogle Scholar
- 31.Alghunaim A, Kirdponpattara S, Newby BMZ. Techniques for determining contact angle and wettability of powders. Powder Technol. Elsevier B.V.; 2016;287:201–15. Available from: https://doi.org/10.1016/j.powtec.2015.10.002
- 33.Wang H, Sun Y, Yang B, Li S. Association between the physical stability of flurbiprofen suspension and the interaction of HPMC/SDS. Asian J Pharm Sci. Elsevier B.V.; 2017;13:63–71. Available from: https://doi.org/10.1016/j.ajps.2017.08.001
- 34.Liu T, Hao J, Yang B, Hu B, Cui Z, Li S. Contact angle measurements: an alternative approach towards understanding the mechanism of increased drug dissolution from ethylcellulose tablets containing surfactant and exploring the relationship between their contact angles and dissolution behaviors. AAPS PharmSciTech. 2018;19:1582–91.CrossRefGoogle Scholar
- 35.Craig DQM. The mechanisms of drug release from solid dispersions in water-soluble polymers. 2002;231:131–144.Google Scholar