Effect of counter-ion agents on metronidazole loaded chitosan microparticles prepared by w/o emulsifcation method

Wiwat Pichayakorn

Medical Products Innovations from Polymers in Clinical Use Research Unit and

Faculty of Pharmaceutical Sciences,Prince of Songkla University,Songkhla 90112,Thailand

Effect of counter-ion agents on metronidazole loaded chitosan microparticles prepared by w/o emulsifcation method

Wiwat Pichayakorn*

Medical Products Innovations from Polymers in Clinical Use Research Unit and

Faculty of Pharmaceutical Sciences,Prince of Songkla University,Songkhla 90112,Thailand

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Chitosan

Microparticles

Counter-ion

Sodium hydroxide

Tripolyphosphate

Chitosan microparticles for controlling drug delivery have been prepared by water in oil(w/o)emulsifcation process.Glutaraldehyde is normally used as cross-linking agent for hardening chitosan polymer into the rigid particles[1].From the cationic charge of ammonium groups in chitosan structure, moreover,it is also possible to cross-link the polymeric chain by the anionic counter-ion substances.Sodium hydroxide (NaOH)and tripolyphosphate(TPP)are the rich negatively charged molecules that are normally used in pharmaceutical preparations.They might be more appropriate to be chosen for the co-crosslinking process due to its safety[2].Therefore,this study aimed to investigate the effect of counter-ion NaOH and TPP agents on the properties of chitosan microparticles crosslinked by glutaraldehyde.Metronidazole was used as model drug loaded in these systems.

Chitosan solution(1%w/w)was emulsifed in soybean oil using 1%w/w Span80 as emulsifying agent.High speed homogenizer at 19,000 rpm was used to reduce the emulsion droplets for 10 minutes.The 25%glutaraldehyde solution was added into the mixture and further mixed by homogenizer for 5 minutes(A),and then the solution of either(B)0.5M NaOH or(C)0.5M TPP was mixed by magnetic stirrer for 30 minutes. Afterwards,the oil phase was fltered-out,washed by either (1)2 times of hexane followed by 3 times of water or(2)5 times of hexane,and fnally dried using a freeze dryer.The morphology was observed by scanning electron microscopy(SEM).The particle size was determined by light scattering technique.Metronidazole was extracted from chitosan microparticles and the drug content was analyzed by UV–visible spectroscopy.Drug release was studied using USP34 dissolution apparatus 2 (paddle)in 200 mL phosphate buffer pH 7.4 at 75 rpm and 37±0.5°C.Metronidazole was in crystal form with micron size as shown in Fig.1(d).In preparation into chitosan microparticles, it was dissolved in chitosan solution before forming w/o emulsion.Therefore,its crystal form disappeared,and the particle sizes of chitosan microparticles were smaller than that of drug crystal.The chitosan microparticles with counter-ion(B and C)showed the smaller particle size and more roughness on thesurface than those without counter-ion(A)(Fig.1).The washing methods revealed the slight difference in the particle surfaces.Washing with hexane and water(1)presented the small crystals of counter-ion on their surfaces resulting in more roughness,while washing with only hexane(2)provided the smoother surfaces.Moreover,washing with hexane and water (1)could dissolve most of drug from the particles resulting to less entrapment effciency,while washing with only hexane (2)provided higher entrapment values.However,the counterion also decreased the entrapment effciency of drug in microparticles.NaOH as counter-ion provided the smallest particles with roughness on the particle surfaces;therefore,the fastest drug release was observed(B2).Particles with TPP(C2) provided the similar character to those without counter-ion(A2), and the similar drug release profle obtained.However,the drug release profles after 2 hours of all preparations were not different.In conclusion,anionic counter-ions such as NaOH and TPP could be added into preparation process of chitosan microparticles by w/o emulsifcation method.However,they slightly affected the surface character,size,drug entrapment effciency and drug release of microparticles.

Fig.1–SEM photographs,particle size,entrapment effciency and drug release profles.Symbols:(A)particles without counter-ion,(B)particles with NaOH,(C)particles with TPP,(1)washing with hexane and water,(2)washing with hexane,(d) metronidazole.

Acknowledgements

The author acknowledges the fnancial support from Prince of Songkla University.The author is also thankful to Miss Siriwan Kerdned for her helpfulness in laboratory.

R E F E R E N C E S

[1]Pichayakorn W,Boonme P.Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment.Mater Sci Eng C 2013;33:1197–1202.

[2]Martins AF,de Oliveira DM,Pereira AGB,et al.Chitosan/TPP microparticles obtained by microemulsion method applied in controlled release of heparin.Int J Bio Macromol 2012;51:1127–1133.

*E-mail address:wiwat.p@psu.ac.th.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.111

1818-0876/©2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).