Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles

Sara Salatin, Jaleh Barar, Mohammad Barzegar-Jalali, Khosro Adibkia, Farhad Kiafar, Mitra Jelvehgari


Rivastigmine hydrogen tartrate (RHT), one of the potential cholinesterase inhibitors, has received great attention as a new drug candidate for the treatment of Alzheimer's disease. However, the bioavailability of RHT from the conventional pharmaceutical forms is low because of the presence of the blood brain barrier. The main aim of the present study was to prepare positively charged Eudragit RL 100 nanoparticles as a model scaffold for providing a sustained release profile for RHT. The formulations were evaluated in terms of particle size, zeta potential, surface morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Drug entrapment efficiency and in vitro release properties of lyophilized nanoparticles were also examined. The resulting formulations were found to be in the size range of 118 nm to 154 nm and zeta potential was positive (+22.5 to 30 mV). Nanoparticles showed the entrapment efficiency from 38.40 ± 8.94 to 62.00 ± 2.78%. An increase in the mean particle size and the entrapment efficiency was observed with an increase in the amount of polymer. The FTIR, XRD, and DSC results ruled out any chemical interaction between the drug and Eudragit RL100 polymer. RHT nanoparticles containing low ratio of polymer to drug (4:1) presented a faster drug release and on the contrary, nanoparticles containing high ratio of polymer to drug (10:1) were able to give a more sustained release of the drug. The study revealed that RHT nanoparticles were capable of releasing the drug in a prolonged period of time and increasing the drug bioavailability.


Rivastigmine hydrogen tartrate; Nanoparticles; Eudragit RL100; Nanoprecipitation

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Zhang C, Wan X, Zheng X, Shao X, Liu Q, Zhang Q, et al. Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice. Biomaterials. 2014;35(1):456-465.

Nazem A, Mansoori GA. Nanotechnology for Alzheimer's disease detection and treatment. Insciences J. 2011;1(4):169-193.

Doggui S, Dao L, Ramassamy C. Potential of drug-loaded nanoparticles for Alzheimer's disease: diagnosis, prevention and treatment. Ther Deliv. 2012;3(9):1025-1027.

Fazil M, Md S, Haque S, Kumar M, Baboota S, Sahni JK, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012;47(1):6-15.

Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev. 2012;64(7):701-705.

Salatin S, Maleki Dizaj S, Yari Khosroushahi A. Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int. 2015;39(8):881-890.

Sahni JK, Doggui S, Ali J, Baboota S, Dao L, Ramassamy C. Neurotherapeutic applications of nanoparticles in Alzheimer's disease. J Control Release. 2011;152(2):208-231.

Salatin S, Jelvehgari M, Maleki-Dizaj S, Adibkia K. A sight on protein-based nanoparticles as drug/gene delivery systems. Ther Deliv. 2015;6(8):1017-1029.

Masserini M. Nanoparticles for brain drug delivery. ISRN biochem. 2013;2013: Article ID 238428, 18 pages.

Behera AK, Barik BB, Pandya S, Joshi S. Formulation and evaluation of Isoniazid loaded-∑-polycaprolactone nanoparticles. J Pharm Res. 2012;5(2):798-802.

Das S, Suresh PK, Desmukh R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine. 2010;6(2):318-323.

Devarajan PV, Sonavane GS. Preparation and in vitro/in vivo evaluation of gliclazide loaded Eudragit nanoparticles as a sustained release carriers. Drug Dev Ind Pharm. 2007;33(2):101-111.

Pignatello R, Bucolo C, Puglisi G. Ocular tolerability of Eudragit RS100® and RL100® nanosuspensions as carriers for ophthalmic controlled drug delivery. J pharm sci. 2002;91(12):2636-2641.

Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55(1):R1-R4.

Quintanar-Guerrero D, Allémann E, Fessi H, Doelker E. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm. 1998;24(12):1113-1128.

Hornig S, Heinze T, Becerbc CR, Schubert US. Synthetic polymeric nanoparticles by nano-precipitation. J Mater Chem. 2009;19(23):3838-3840.

Chin SF, Azman A, Pang SC. Size controlled synthesis of starch nanoparticles by a microemulsion method. J Nanomater. 2014;2014: Article ID 763736, 7 pages.

Adhikari U, Goliaei A, Tsereteli L, Berkowitz ML. Properties of poloxamer molecules and poloxamer micelles dissolved in water and next to lipid bilayers: results from computer simulations. J Phys Chem B. 2016;120(26):5823-5830.

Amini H, Ahmadiani A. High-performance liquid chromatographic determination of rivastigmine in human plasma for application in pharmacokinetic studies. Iran J Pharm Res. 2010;9(2):115-121.

Pagar K, Vavia P. Rivastigmine-loaded L-lactide-depsipeptide polymeric nanoparticles: decisive formulation variable optimization. Sci Pharm. 2013;81(3):865-885.

Joshi SA, Chavhan SS, Sawant KK. Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm. 2010;76(2):189-199.

Betancourt T, Brown B, Brannon-Peppas L. Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in vitro evaluation. Nanomedicine (Lond). 2007;2(2):219-232.

Loveymi BD, Jelvehgari M, Zakeri-Milani P, Valizadeh H. Design of vancomycin RS-100 nanoparticles in order to increase the intestinal permeability. Adv Pharm Bull. 2012;2(1):43-56.

Sah E, Sah H. Recent trends in preparation of poly (lactide-co-glycolide) nanoparticles by mixing polymeric organic solution with antisolvent. J Nanomater. 2015;2015: Article ID 794601, 22 pages.

Verma P, Gupta RN, Jha AK, Pandey R. Development, in vitro and in vivo characterization of Eudragit RL 100 nanoparticles for improved ocular bioavailability of acetazolamide. Drug Deliv. 2013;20(7):269-276.

Miladi K, Ibraheem D, Iqbal M, Sfar S, Fessi H, Elaissari A. Particles from preformed polymers as carriers for drug delivery. EXCLI J. 2014;13:28-57.

Katara R, Majumdar DK. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf B Biointerfaces. 2013;103:455-462.

Seremeta KP, Chiappetta DA, Sosnik A.. Poly (εcaprolactone) Eudragit RS100 and] Poly (ε-caprolactone), Eudragit RS100 Blend submicron particles for the sustained release of the antiretroviral efavirenz. Colloids Surf B Biointerfaces.. 2013;102:441-449.

Govender T, Stolnik S, Garnett MC, Illum L, Davis SS. PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release. 1999;57(2):171-185.

Bilati U, Allémann E, Doelker E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci. 2005;24(1):67-75.

Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm. 1999;25(4):471-476.

Alshamsan A. Nanoprecipitation is more efficient than emulsion solvent evaporation method to encapsulate cucurbitacin I in PLGA nanoparticles. Saudi Pharm J. 2014;22(3):219-222.

Emami J, Shetab Boushehri MS, Varshosaz J. Preparation, characterization and optimization of glipizide controlled release nanoparticles. Res Pharm Sci, 2014;9(5):301-314.

Bilati U, Allémann E, Doelker E. Nanoprecipitation versus emulsion-based techniques for the encapsulation of proteins into biodegradable nanoparticles and process-related stability issues. AAPS PharmSciTech. 2005;6(4):E594-E604.

Peltonen L, Aitta J, Hyvönen S, Karjalainen M, Hirvonen J.Improved entrapment efficiency of hydrophilic drug substance during nano-precipitation of poly(l)lactide nanoparticles. AAPS PharmSciTech. 2004;5(1):E16.

Yadav SK, Mishra S, Mishra B. Eudragit-based nanosuspension of poorly water-soluble drug: formulation and in vitro–in vivo evaluation. AAPS PharmSciTech. 2012;13(4):1031-1044.

Sahu BP, Das MK. Nanosuspension for enhancement of oral bioavailability of felodipine. Appl Nanosci. 2014;4(2):189-197.

Emami J, Kazemali MR. Design and in vitro evaluation of a novel controlled onset extended-release delivery system of metoprolol tartrate. Res Pharm Sci. 2016;11(1):81-92.

Sharma D, Maheshwari D, Philip G, Rana R, Bhatia S, Singh M, et al. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: in vitro and in vivo evaluation. BioMed Res Int. 2014;2014: Article ID 156010, 14 pages.

Sutradhar KB, Khatun S, Luna IP. Increasing possibilities of nanosuspension. J Nanotechnol. 2013;2013: Article ID 346581, 12 pages.


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