PHYSICOCHEMICAL CHARACTERIZATION AND EVALUATION OF TELMISARTAN: HYDROXYPROPYL-β-CYCLODEXTRIN: TWEEN 80 INCLUSION COMPLEX
DOI:
https://doi.org/10.22159/ijpps.2017v9i9.19058Keywords:
Cyclodextrin, Telmisartan, Ternary complex, Stability, Tween 80, Calorimetry, DOCAAbstract
Objective: The present work was aimed to study the effect of the ternary component on complexation efficiency of cyclodextrins towards telmisartan which is a poorly soluble anti-hypertensive agent.
Methods: The elucidation of inclusion complexation of telmisartan (TEL) with hydroxypropyl-β-cyclodextrin (HP-β-CD) in the presence and absence of tween 80 was done by investigating their interactions in solid and solution state. The solid state characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD) fourier transform infra-red spectroscopy (FTIR) studies. The host guest stoichiometry was confirmed in solution state by proton nuclear magnetic resonance (1HNMR) and solution calorimetry studies. The improvement in solubility was evaluated through dissolution studies, which was further confirmed by in vivo studies.
Results: In solution state, the phase solubility studies indicated 1:1 stoichiometry between TEL and HP-β-CD both in presence and absence of tween 80. The NMR and molecular modelling studies indicated the insertion of N-methyl benzimidazole and biphenyl carboxylate regions of TEL into HP-β-CD cavity suggesting the coexistence of two 1:1 complexes in equilibrium with each other. The stability constants, K1 (imidazole region of TEL-CD) and K2 (biphenyl acetic acid region of TEL-CD), were enhanced in the presence of tween 80 as evident by the higher value of stability constants. Efficacy of ternary complex was established by a significant decrease in the systolic blood pressure of deoxycorticosterone acetate (DOCA) induced hypertensive rats.
Conclusion: It can be concluded that solubility of TEL was increased by encapsulation with HP-β-CD. Tween 80 further increased the complexation efficiency and decreased the bulk of cyclodextrin.
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Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: the past, present and future. Nat Rev Drug Discovery 2005;12:1023-35
Loftsson T, Pekka J, Mar M, Tomi J. Cyclodextrins in drug delivery. Macroc Chem 2002;44:213-8.
Martin Del VEM. Cyclodextrins and their uses: a review. Process Biochem 2004;39:1033–46.
Yadav N, Chhabra G, Pathak K. Enhancement of solubility and dissolution rate of a poorly water soluble drug using single and double hydrophilization approach. Int J Pharm Pharm Sci 2012;4:975-1491.
Thompson DO. Cyclodextrins enabling excipients: their present and future use in pharmaceuticals. Crit Rev Ther Drug 1997;14:1-104.
Stella VJ, Rajewski R. Cyclodextrins: Their future in drug formulation and delivery. Pharm Res 1997;14:556-67.
Heise HM, Kuckuk R, Bereck A, Riegel D. Infrared spectroscopy and Raman spectroscopy of cyclodextrin derivatives and their ferrocene inclusion complexes. Vib Spectrosc 2010;53:19-23.
Smith JS, Macrae RJ, Snowden MJ. Effect of SBE7-β-cyclodextrin complexation on carbamazepine release from sustained release beads. Eur J Pharm Sci 2005;60:73-80.
Mendhe AA, Kharwade RS, Mahajan UN. Dissolution enhancement of poorly water-soluble drug by cyclodextrins inclusion complexation. Int J Appl Pharm 2016;8:60-5.
Lakshmana PVR, Rambabu C. Use of ion association complex formation for the spectrophotometric determination of itopride HCL in bulk and its pharmaceutical preparations. Int J Curr Pharm Res 2017;9:81-4.
Sarangi MK, Padhi S. Colon targeted drug delivery system-an approach for treating colonic ailments. J Crit Rev 2015;2:12-8.
Harika K, Sunitha K, Pavan Kumar P, Madhusudan Rao Y. Influence of hydroxypropyl-β-cyclodextrin on repaglinide release from sustained release bio adhesive buccal tablets. Asian J Pharm Clin Res 2013;6:184-90.
Al-Nuss Raghad, El-Zein Hind. Enhancement of candesartan cilexetil dissolution rate by using different methods. Asian J Pharm Clin Res 2015;8:320-6.
Loftsson T, Fridriksdóttir H. The effect of water-soluble polymers on the aqueous solubility and complexing abilities of β-cyclodextrin. Int J Pharm 1998;163:115-21.
Lahiani M, Barbot C, Bounoure F, Joudieh S, Skiba M. Solubility and dissolution rate of progesterone-cyclodextrin-polymer systems. Drug Dev Ind Pharm 2006;32:1043-58.
Ribeiro LSS, Ferreira DC, Veiga FJB. Physicochemical investigation of the effects of water-soluble polymers on vipocetine complexation with β-cyclodextrin and its sulfonyl ether derivative in solution and solid state. Eur J Pharm Sci 2003;20:253-66.
Lofttson T, Hreinsdóttir D, Másson M. Evaluation of cyclodextrin solubilization of drugs. Int J Pharm 2005b;302:18-28.
Messner M, Kurkov SV, Flavia`-Piera R, Brewster ME, Loftsson T. Self-assembly of cyclodextrins: the effect of the guest molecule. Int J Pharm 2011;408:235–47.
Becket G, Schep LJ, Tan MY. Improvement of the in vitro dissolution of praziquantal by complexation with alpha-, beta and gamma cyclodextrins. Int J Pharm 1999;179:65–71.
Challa R, Ahuja A, Ali J, Khar R. Cyclodextrin in drug delivery: an updated review. AAPS Pharm SciTech 2005;6:329–57.
Castagne D, Dive G, Evrard B, Fre´de´rich M, Piel G. Spectroscopic studies and molecular modelling for understanding the interactions between cholesterol and cyclodextrins. J Pharm Pharm Sci 2010;13:362–77.
Kang J, Kumar V, Yang D, Chowdhury PR, Hohl RJ. Cyclodextrin complexation: influence on the solubility, stability, and cytotoxicity of camptothecin, an antineoplastic agent. Eur J Pharm Sci 2002;15:163–70.
Londhe V, Nagarsenker M. Comparision between Hydroxy-propyl-β-cyclodextrin and polyvinyl pyrrolidine as carriers for carbamazepine solid dispersions. Indian J Pharm Sci 1999;61:237–40.
Nalawade P, Aware B, Dand N, Kadam V, Hirlekar R. Solid state characterization of the inclusion complex of valsartan with methyl-β-cyclodextrin. J Inclusion Phenom Macrocyclic Chem 2009;65:377–8.
Carrier RL, Miller LA, Ahmed I. The utility of cyclodextrins for enhancing oral bioavailability. J Controlled Release 2007;123: 78–99.
Loftsson T, Sigurdardóttir AM. The effect of hydroxypropyl methylcellulose on hydroxypropyl-β-cyclodextrin complexation of hydrocortisone and its permeability through hair mouse skin. Eur J Pharm Sci 1994;2:297-301.
Loftsson T, Vogensen S, Brewster ME, Konraosdottir F. Effects of cyclodextrins on drug delivery through biological membranes. J Pharm Sci 2007;10:2532–46.
Uekama K. Design and evaluation of cyclodextrin based drug formulation. Chem Pharm Bull 2004;8:900–15.
Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem Instrum 1965;4:117–22.
Chadha R, Arora P, Gupta S, Jain DVS. Complexation of nevirapine with cyclodextrins in the presence and absence of tween 80:Characterization, thermodynamic parameters, and permeability flux. J Therm Anal Calorin 2011;105:1049–59.
Chadha R, Jain DVS, Aggarawal A, Singh S, Thakur D. Binding constants of inclusion complexes of nitroimidazoles with β-cyclodextrins in the absence and presence of PVP. Thermochim Acta 2007;459:111–5.
Chadha R, Gupta S, Shukla G, Jain DVS, Pissurlenkar RRS, Coutinho EC. Interaction of artesunate with β cyclodextrins: Characterisation, thermodynamic parameters, molecular modelling, the effect of PEG on complexation and antimalarial activity. Results Pharma Sci 2011;1:38-48.
Grillo R, De Melo NFS, Morales Moraes C, De Limba R, Menezes CMS, Ferreira EI, et al. Study of the interaction between hydroxymethyl nitrofurazone and 2-hydroxy-β-cyclodextrin. J Pharm Biomed Anal 2008;47:295-302.
Kane RN, Kuchekar BS. Preparation, physicochemical characterization, dissolution and formulation studies of telmisartan cyclodextrin inclusion complexes. Asian J Pharm 2010;4:52-9.
Muankaew C, Jansook P, Sigurđsson HH, Loftsson T. Cyclodextrin-based telmisartan ophthalmic suspension: formulation development for water-insoluble drugs. Int J Pharm 2016;30:21-31.
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