aSchool of Pharmacy,Walailak University,Thasala,Nakhon Si Thammarat 80161,Thailand

bDrug and Cosmetic Research and Development Unit,Walailak University,Thasala,Nakhon Si Thammarat 80161,Thailand

Inclusion complexes between sildenafl citrate and cyclodextrins enhance drug solubility

Apichart Atipairina,b,*,Somchai Sawatdeea,b

aSchool of Pharmacy,Walailak University,Thasala,Nakhon Si Thammarat 80161,Thailand

bDrug and Cosmetic Research and Development Unit,Walailak University,Thasala,Nakhon Si Thammarat 80161,Thailand

A R T I C L E I N F O

Article history:

Available online 25 November 2015

Cyclodextrins

Inclusion complex

Sildenafl

Solubility

Sildenafl citrate is a potent and selective phosphodiesterase-5 inhibitor.It is effectively used in the treatment of erectile dysfunction and pulmonary arterial hypertension.The drug is rapidly absorbed and pharmacologically acts within 30 min to 1 h after oral administration.However,it has a relatively low absolute bioavailability of 41%because its limited solubility in water is the major problem[1].To improve the oral bioavailability of poorly water-soluble drugs, cyclodextrins are widely used as pharmaceutical solubilizer [2].

The present study was to investigate the inclusion complexations between sildenafl citrate and cyclodextrins (alpha-CD,hydroxy-beta-CD,and gamma-CD)in the solution state.The UV spectroscopic measurement of complexes between sildenafl(30 μM)and CDs showed the shift of the absorption spectra by which changing the concentrations of all CDs from 0 to 10 mM resulted in an increase in the absorbance of the drug without any shifts of λmax.This indicated the guest–host complex interaction between sildenafl and three CDs.Furthermore,the phase solubility profle showed that the solubility of the drug increased as a linear function of the CD concentration.It was defned as AL-type relationship,indicating a one-to-one complex formation[3]. The solubilizing power of the CDs toward the drug was in the following order:alpha-CD>hydroxy-beta-CD>gamma-CD, where K1:1values at pH 4.5 and 30°C were 13.20±0.68, 7.97±0.60,and 4.08±0.60 M?1(Fig.1),respectively.These emphasize that the inclusion complexes between sildenafl citrate and cyclodextrins enhance drug solubility and might be a means for further drug formulation to increase its bioavailability.

Acknowledgements

The authors acknowledged the fnancial support received from Walailak University.In addition,we would like to thank the Center of Scientifc andTechnological Equipments,Walailak University,for research facilities.

Fig.1–Phase solubility diagram of sildenafl(30 μM)in the presence of alpha-CD,hydroxyl-beta-CD,and gamma-CD over a concentration range of 0–50 mM at 30°C and pH 4.5.

R E F E R E N C E S

[1]Nichols DJ,Muirhead GJ,Harness JA.Pharmacokinetics of sildenafl after single oral doses in healthy male subjects: absolute bioavailability,food effects and dose proportionality. Br J Clin Pharmacol 2002;53(Suppl.1):5S–12S.

[2]Brewster ME,Loftsson T.Cyclodextrins as pharmaceutical solubilizers.Adv Drug Deliv Rev 2007;59(7):645–666.

[3]Al Omari MM,Zughul MB,Davies JE,et al.Sildenafl/ cyclodextrin complexation:stability constants, thermodynamics,and guest-host interactions probed by 1H NMR and molecular modeling studies.J Pharm Biomed Anal 2006;41(3):857–865.

*E-mail address:apichart.at@wu.ac.th.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.11.105

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/).