Aripiprazole-Cyclodextrin Binary Systems for Dissolution Enhancement: Effect of Preparation Technique, Cyclodextrin Type and Molar Ratio

Document Type : Original Article

Authors

1 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, KSA 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo Egypt

2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, KSA,Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

3 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

Abstract

 




Objective(s):
The aim of this work was to investigate the effect of the natural and the chemically modified form of cyclodextrins namely; β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) respectively on the solubility and dissolution rate of aripiprazole; an antipsychotic medication showing poor aqueous solubility.
 
Materials and Methods:
Phase solubility of aripiprazole with the studied CDs and the complexation efficiency values (CE) which reflect the solubilizing power of the CDs towards the drug was performed. Solid binary systems of aripiprazole with CDs were prepared by kneading, microwave irradiation and freeze-drying techniques at 1:1 and 1:2 (drug to CD) molar ratios. Drug-CD physical mixtures were also prepared in the same molar ratios for comparison. The dissolution of aripiprazole-binary systems was carried out to select the most appropriate CD type, molar ratio and preparation technique.
Results:
Phase solubility study indicated formation of higher order complexes and the complexation efficiency values was higher for HP-β-CD compared to β-CD. Drug dissolution study revealed that aripiprazole dissolution was increased upon increasing the CD molar ratio and, the freeze-drying technique was superior to the other studied methods especially when combined with the HP-β-CD. The cyclodextrin type, preparation technique and molar ratio exhibited statistically significant effect on the drug dissolution at P≤ 0.05.
Conclusion:
The freeze-dried system prepared at molar ratio 1:2 (drug: CD) can be considered as efficient tool for enhancing aripiprazole dissolution with the possibility of improving its bioavailability

Keywords

References

 
1. Pinnamaneni S, Das NG, Das SK. Formulation approaches for orally administered poorly soluble drugs. Pharmazie 2002; 57
: 291–300.
2. Chingunpituk J. Nanosuspension technology for Drug delivery. J Sci & Tech, 2007; 4
:139-153.
3. Wolfgang J. Improving drug solubility for oral delivery using solid dispersions
. Eur J Pharm Biopharm 2000; 50:47-60.
4. Juppo AM, Boissier C, Khoo C. Evaluation of solid dispersion particles prepared by SEDDS. Int J Pharm 2003; 250
:385-401 .
5. Roux M, Perly B, Djedaini-Pilard F. Self-assemblies of amphiphilic cyclodextrins. Eur Biophys J 2007; 36
:861-867.
6. Loftsson T, Duchene D. Cyclodextrins and their applications. Int J Pharm 2007; 329:1-11
.
7. Duches D, Vaution C, Glomot F. Cyclodexterin: Their Value in Pharmaceutical Technology. Drug Dev Ind Pharm 1988; 12:11-13.
8. Fernandes CM, Veiga FJB. Effect of the hydrophobic nature of triacetyl-β-cyclodextrin on the complexation with nicardipine hydrochloride: physicochemical and dissolution properties of the kneaded and spray-dried complexes. Chem Pharm Bull 2002; 50:1597-1602
.
9. Cirri M, Rangoni C, Maestrelli F, Corti G, Mura P. Development of fast-dissolving tablets of flurbiprofen-cyclodextrin complexes. Drug Dev Ind Pharm 2005; 31:697-707
.
10. Cunha-Filho MSS, Dacunha-Marinho B, Torres- Labandeira JJ, Martinez-Pacheco R, Landin M. Characterization of β-lapachone and methylated β-cyclodextrin solid-state systems. AAPS Pharm Sci Tech 2007; 8:1-10
.
11. Moyano JR, Ginés JM, Arias MJ, Rabasco AM. Study of the dissolution characteristics of oxazepam via complexation with β-cyclodextrin. Int J Pharm 1995; 114:95-102
.
12. Murthy TEGK, Sowjanya G. Evaluation of some methods for preparing carvedilol-hydroxyl propyl- β - cyclodextrin inclusion complexes. Asian J Biochem Pharm Res 2011; 2:676-683.
13. Parikh RK, Mansuri NS, Gohel MC, Sonlwala MM. Dissolution enhancement of Nimesulide Using Complexation and Salt Formation Techniques. Indian Drugs 2005; 42:149-53.
14. Doijad RC, Kanakal MM, Manvi IV. Studies on piroxicam-beta-cyclodextrin inclusion complexes. Indian Pharm 2007; 94-98
.
15. Friedrich H, Nada A, Bodmier R. Solid state and dissolution rate characterization of co-ground mixtures of nifedipine and hydrophillic carriers. Drug Dev Ind Pharm 2005; 31:719-28
.
16. Vozone CM, Marques HMC. Complexation of budesonide in cyclodextrins and particle aerodynamic characterization of the complex solid form for dry powder inhalation. J Incl Phenom Macrocycl Chem 2003; 44:111-115
.
17. Cao FT, Guo J, Ping Q. The physicochemical characteristics of freeze-dried scutellarin- cyclodextrin tetracomponent complexes. Drug Dev Ind Pharm 2005; 31:747-756
.
18. Wen X, Tan F, Jing Z, Iiu Z. Prepration and study of the 1:2 inclusion complex of carvedilol with β - cyclodextrin. J Pharm Biomed Anal 2004; 34:517- 523
.
19. Deshmukh SS, Potnis VV, Shelar DB, Mahaparale PR. Studies on inclusion complexes of ziprasidone hydrochloride with beta-cyclodextrin and hydroxypropyl beta-cyclodextrin. Indian Drugs 2007; 44:677-682
.
20. Ranpise NS, Kulkarni NS, Mair PD, Ranade AN. Improvement of water solubility and
invitro dissolution rate of aceclofenac by complexation with β-cyclodextrin and hydroxypropyl- β-cyclodextrin. Drug Dev Ind Pharm 2010; 15:64-70.
21. Al-Marzouqui AH, Jobe B, Dowaidar AF, Maestrelli F, Mura P. Evaluation of supercritical fluid technology as preparative technique of benzocainecyclodextrin
Aripiprazole-Cyclodextrin Binary Systems Badr-Eldin et al
Iran J Basic Med Sci, Vol. 16, No. 12, Dec 2013
 
1231
　
complexes-Comparison with conventional methods . J Pharm Biomed Anal 2007; 43
: 566-574.
22. Charoenchaitrakool M, Dehghani F, Foster NR. Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl- betacyclodextrin. Int J Pharm 2009; 239
: 103-112.
23. Burris KD, Molski TF, Xu C. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302
:381-389.
24. Higuchi T, Connors KA. Phase solubility techniques. In: Reilly CN. editor. Advances in Analytical and Chemistry Instrumentation. New York: Wiley Inter-science;Vol. 4. 1965.p. 117-212
.
25. Dey S, Chauhan N, Malairajan P, Murugan R, Das RC, Ahmad S. A simple and rapid spectrophotometric determination of aripiprazole in pharmaceutical dosage form. Int J Drug Dev Res 2011; 3:205-208
.
26. Loftsson T, Masson M, Sigurjonsdottir JF. Methods to enhance the complexation efficiency of cyclodextrin. S.T.P. Pharma Sci. 9, 237-242 through Loftsson, T., Hreinsdóttir, D. and Másson, M. 2005. Evaluation of cyclodextrin solubilization of drugs. Int J Pharm 1999; 302:18-28
.
27. Nagarsenker MS, Joshi MS. Celecoxib-cyclodextrin systems: characterization and evaluation of
in vitro and in vivo advantage. Drug Dev Ind Pharm 2005; 31:169-178.
28. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975; 27:48-49.
29. Loftsson T, Masson M, Brewster ME. Self association of cyclodextrin and cyclodextrin complexes. J Pharm Sci 2004; 93:1091-1099
.
30. Pascal B, Maud G, Georges D, Adelin A, Valery B, Bruno P,
et al. The effect of cyclodextrins on the aqueous solubility of a new MMP inhibitor: phase solubility, 1H-NMR spectroscopy and molecular modeling studies, preparation and stability studies of nebulizable solutions. J Pharm Pharm Sci 2005; 8:164-175.
31. Figueiras A, Sarraguça JMG, Carvalho RA, Pais AACC, Veiga FJB. Interaction of omeprazole with a methylated derivative of β-cyclodextrin: Phase solubility, NMR spectroscopy and molecular simulation. Pharm Res 2007; 24:377-389.
32. Arima H, Yunomae K, Miyake K, Irie T, Hirayama F, Uekama K. Comparative studies of the enhancing effects of cyclodextrins on the solubility and oral bioavailability of tacrolimus in rats. J Pharm Sci 2001; 90:690-701
.
33. Loftsson T, Magnúsdóttir A, Másson M, Sigurjónsdóttir JF. Self association and cyclodextrin solubilization of drugs. J Pharm Sci 2002; 91:2307-2316.
34. Bhosale AV, Hardikar SR, Jagtap RS, Patil NB, Dhawale SS, Shirsath SC. Formulation of beta cyclodextrin complexed controlled release matrix tablet of glipizide and its
in-vitro evaluation. Int J
PharmTech Res 2009; 1:773-778.
35. Nicolescu C, Aramă C, Nedelcu A, Monciu C. Phase solubility studies of the inclusion complexes of repaglinide with β-cyclodextrin and β-cyclodextrin derivatives. Farmacia 2010; 58:620-628.
36. Ramnik S, Nitin B, Jyotsana M, Hiremath SN. Characterization of cyclodextrin inclusion complexes a review. J Pharm Sci Tech 2010; 2:171-183.
37. Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified beta cyclodextrins - I: Preparation and
in-vitro evaluation. Eur J Pharm Biopharm 2008; 70:819-827.
38. Hara T, Hirayama F, Arima H, Yamaguchi Y, Uekama K. Improvement of solubility and oral bioavailability of 2-(N-cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) with antidiabetic and lipid-lowering activities in dogs by 2-hydroxypropyl- β-cyclodextrin. Chem Pharm Bull 2006; 54:344-349
.
39. Zingone G, Rubessa F. Preformulation study of the inclusion complex of warfarin-β-cyclodextrin. Int J Pharm 2005; 291:3-10.
40. Betageri GV, Makarla KR. Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques. Int J Pharm 1995; 126:155-160
.
41. Loftsson T, Sigurdsson HH, Másson M, Schipper N. Preparation of solid drug/cyclodextrin complexes of acidic and basic drugs. Pharmazie 2004; 59:25-29
.
42. Johnson JLH, He Y, Jain A, Yalkowsky SH. Improving cyclodextrin complexation of a new antihepatitis drug with glacial acetic acid. AAPS Pharm Sci Tech 2006; 7:E1-E6
.
43. Balata G, Mahdi M, Abu Bakera R. Improvement of solubility and dissolution properties of Ketoconazole by solid dispersions and inclusion complexes. Asian J Pharm Sci 2010; 5:1-12.
44.
Mihajlovic T, Kachrimanis K, Graovac A, Djuric Z, Ibric S. Improvement of aripiprazole solubility by complexation with (2-hydroxy)propyl-β-cyclodextrin using spray drying technique. AAPS Pharm Sci Tech 2012; 13:623-631
45. Bayomi MA, Abanumany KA, Al-Angary AA. Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state. Int J Pharm 2002; 243:107-117.
46. Rajendrakumar K, Madhusudan S, Pralhad T. Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity in rat. Eur J Pharm Biopharm 2005; 60:39-46
.
47. Khodaverdi E, Khalili N, Zangiabadi F, Homayouni A. Preparation, characterization and stability studies of glassy solid dispersions of indomethacin using PVP and isomalt as carriers. Iran J Basic Med Sci 2012; 15:820-832.
Iranian Journal of Basic Medical Sciences
Volume 16, Issue 12 - Serial Number 12
December 2013
Pages 1223-1231

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