Preparation and characterization of ethylcellulose microspheres for sustained-release of pregabalin

Haya Yasin , Bashar Al-Taani, Mutaz Sheikh Salem


Background and purpose: Pregabalin is used in the treatment of epilepsy, chronic pain, and other psychological disorders. Preparation of pregabalin in the sustained-release formulation will enhance patient compliance and reduce the incidence of side effects. The aim of this study was to prepare sustained-release microspheres for pregabalin utilizing ethylcellulose and evaluate the processing factors that influence the fabrication and the performance of the prepared microspheres.

Experimental approach: The microspheres were prepared using the water-oil-oil double emulsion solvent evaporation method. Microspheres were characterized for particle size, encapsulation efficiency, and in vitro drug release. The influence of the processing variables on the characteristics of the prepared microspheres was studied. Microspheres solid-state characterization performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy.

Findings/Results: The results described in the context of the current work illustrated the suitability of the water-oil-oil system in the preparation of sustained-release microspheres for pregabalin. The optimum formulation was prepared at a drug to polymer ratio of 1:3 w/w, stirring speed of 600 rpm, surfactant concentration of 1.5%, and external phase volume of 150 mL. This formula produced microspheres particle size in the range 600-1000 µm, with 87.6% yield, and 80.14 ± 0.53% encapsulation efficiency. Drug release from the microspheres was found to be diffusion controlled, with a pH-independent behavior.

Conclusion and implication

The current work presented a successful attempt to fabricate a sustained-release microsphere comprising pregabalin. This will help overcome the frequent dosing problems with conventional pregabalin dosage forms and improve product performance.




Double emulsion; Ethylcellulose; Microsphere; Pregabalin; Solvent evaporation.

Full Text:



Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173.

DOI: 10.1016/S1474-4422(14)70251-0.

Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328-335.

DOI: 10.1155/2014/754693.

Vinik A. Clinical review: use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy. J Clin Endocrinol Metab. 2005;90(8):4936-4945.

DOI: 10.1210/jc.2004-2376.

Salimzade A, Hosseini-Sharifabad A, Rabbani M. Comparative effects of chronic administrations of gabapentin, pregabalin and baclofen on rat memory using object recognition test. Res Pharm Sci. 2017;12(3):204-210.

DOI: 10.4103/1735-5362.207201.

Fedak Romanowski EM. Book review: pellock’s pediatric epilepsy diagnosis and therapy. J Child Neurol. 2017;32(9):846-847.

DOI: 10.1177/0883073817711528.

Bruschi ML. Strategies to modify the drug release from pharmaceutical systems. Amsterdam: Elsevier/Woodhead Publishing; 2017. pp: 87-194.

DOI: 10.1016/C2014-0-02342-8.

Kim S, Hwang KM, Park YS, Nguyen TT, Park ES. Preparation and evaluation of non-effervescent gastroretentive tablets containing pregabalin for once-daily administration and dose proportional pharmacokinetics. Int J Pharm. 2018;550(1-2):160-169.

DOI: 10.1016/j.ijpharm.2018.08.038.

Singh MN, Hemant KS, Ram M, Shivakumar HG. Microencapsulation: a promising technique for controlled drug delivery. Res Pharm Sci. 2010;5(2):65-77.

Venkatesan P, Manavalan R, Valliappan K. Preparation and evaluation of sustained release loxoprofen loaded microspheres. J Basic Clin Pharm. 2011;2(3):159-162.

Parmar H, Sunil B, Nayan G, Bhushan R, Sunil P. Different methods of formulation and evaluation of mucoadhesive microsphere. Int J Appl Biol Pharm Technol. 2010;3:1157-1167.

Kasawar GB, Farooqui MN. Development and validation of HPLC method for the determination of pregabalin in capsules. Indian J Pharm Sci. 2010;72(4):517-519.

DOI: 10.4103/0250-474X.73935.

Ghumman SA, Bashir S, Noreen S, Khan AM, Malik MZ. Taro-corms mucilage-alginate microspheres for the sustained release of pregabalin: in vitro &in vivo evaluation. Int J Biol Macromol. 2019;139:1191-1202.

DOI: 10.1016/j.ijbiomac.2019.08.100.

Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1-18.

DOI: 10.1016/j.colsurfb.2009.09.001.

Berkland C, King M, Cox A, Kim K, Pack DW. Precise control of PLG microsphere size provides enhanced control of drug release rate. J Control Release. 2002;82(1):137-147.

DOI: 10.1016/s0168-3659(02)00136-0.

Ranjha NM, Khan H, Naseem S. Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent. J Mater Sci Mater Med. 2010;21(5):1621-1630.

DOI: 10.1007/s10856-010-4034-4.

Taghipour B, Yakhchali M, Haririan I, Tamaddon AM, Mohammadi Samani S. The effects of technical and compositional variables on the size and release profile of bovine serum albumin from PLGA based particulate systems. Res Pharm Sci. 2014;9(6):407-420.

Jain NK. Controlled novel drug delivery. 1st ed. New Delhi: CBS Publishers and Distributors; 2002. pp: 236-255.

Huang W, Tsui CP, Tang CY, Gu L. Effects of compositional tailoring on drug delivery behaviours of silica xerogel/polymer core-shell composite nanoparticles. Sci Rep. 2018;8(1):13002. 1-13.

DOI: 10.1038/s41598-018-31070-9.

Banerjee S, Siddiqui L, Bhattacharya SS, Kaity S, Ghosh A, Chattopadhyay P, et al. Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application. Int J Biol Macromol. 2012;50(1):198-206.

DOI: 10.1016/j.ijbiomac.2011.10.020.

Paterson TE, Gigliobianco G, Sherborne C, Green NH, Dugan JM, MacNeil S, et al. Porous microspheres support mesenchymal progenitor cell ingrowth and stimulate angiogenesis. APL Bioeng. 2018;2(2):026103,1-19.

DOI: 10.1063/1.5008556.

Heng PW, Chan LW, Easterbrook MG, Li X. Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets. J Control Release. 2001;76(1-2):39-49.

DOI: 10.1016/s0168-3659(01)00410-2.

Mateovic T, Kriznar B, Bogataj M, Mrhar A. The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres. J Microencapsul. 2002;19(1):29-36.

DOI: 10.1080/02652040010055289.

Jelvehgari M, Nokhodchi A, Rezapour M, Valizadeh H. Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method. Indian J Pharm Sci. 2010;72(1):72-78.

DOI: 10.4103/0250-474X.62251.

Pachuau L, Bhaskar M. A study on the effects of different surfactants on ethylcellulose microspheres. Int J PharmTech Res. 2009;1(4):966-971.

Maji R, Ray S, Das B, Nayak AK. Ethyl cellulose microparticles containing metformin HCl by emulsification-solvent evaporation technique: effect of formulation variables. Int Sch Res Notices. 2012;2012:801827,1-6.

DOI: 10.5402/2012/801827.

Jelvehgari M, Maghsoodi M, Nemati H. Development of theophylline floating microballoons using cellulose acetate butyrate and/or Eudragit RL 100 polymers with different permeability characteristics. Res Pharm Sci. 2010;5(1):29-39.

Akbari J, Enayatifard R, Saeedi M, Saghaf M. Influence of hydroxypropyl methylcellulose molecular weight grade on water uptake, erosion and drug release properties of diclofenac sodium matrix tablets. Trop J Pharm Res. 2011;10(5):535-541.

DOI: 10.4314/tjpr.v10i5.1.

Heiskanen H, Peter D, Markku H, Paivi P, Marita O. Effect of physical properties and emulsification conditions on the microsphere size prepared using a solvent extraction process. J Dispers Sci Technol. 2012;33(2):234-244.

DOI: 10.1080/01932691.2011.561166.

Fu X, Ping Q, Gao Y. Effects of formulation factors on encapsulation efficiency and release behavior in vitro of huperzine A-PLGA microspheres. J Microencapsul. 2005;22(7):705-714.

DOI: 10.1080/02652040500162196.

Mao S, Xu J, Cai C, Germershaus O, Schaper A, Kissel T. Effect of WOW process parameters on morphology and burst release of FITC-dextran loaded PLGA microspheres. Int J Pharm. 2007;334(1-2):137-148.

DOI: 10.1016/j.ijpharm.2006.10.036.

Rahman Z, Zidan AS, Habib MJ, Khan MA. Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design. Int J Pharm. 2010;389(1-2):186-194.

DOI: 10.1016/j.ijpharm.2009.12.040.

Dhakar RC, Maurya SD, Sagar BPS, Bhagat S, Prajapati SK, Jain CP. Variables influencing the drug entrapment efficiency of microspheres: a pharmaceutical review. Pharm Lett. 2010;2(5):102-106.

Bhargav A, Babu DJM, Babu BN. Formulation and evaluation of pregabalin microencapsules: a sustained release approach. IJRPB. 2017,5(1):31-35.

Kavanagh N, Corrigan OI. Swelling and erosion properties of hydroxypropylmethylcellulose (Hypromellose) matrices-influence of agitation rate and dissolution medium composition. Int J Pharm. 2004;279(1-2):141-152.

DOI: 10.1016/j.ijpharm.2004.04.016.

Ghosh Dastidar D, Saha S, Chowdhury M. Porous microspheres: synthesis, characterisation and applications in pharmaceutical & medical fields. Int J Pharm. 2018;548(1):34-48.

DOI: 10.1016/j.ijpharm.2018.06.015.

Chaisri W, Ghassemi AH, Hennink WE, Okonogi S. Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters. Colloids Surf B Biointerfaces. 2011;84(2):508-514.

DOI: 10.1016/j.colsurfb.2011.02.006.

Dinarvand R, Moghadam SH, Mohammadyari-Fard L, Atyabi F. Preparation of biodegradable microspheres and matrix devices containing naltrexone. AAPS PharmSciTech. 2003;4(3):45-54.

DOI: 10.1208/pt040334.

Jose S, Fangueiro JF, Smitha J, Cinu TA, Chacko AJ, Premaletha K, et al. Predictive modeling of insulin release profile from cross-linked chitosan microspheres. Eur J Med Chem. 2013;60:249-253.

DOI: 10.1016/j.ejmech.2012.12.011.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.