Pharmaceutical Advances in Cyclodextrin Inclusion Complexes for Improved Bioavailability of Poorly-Soluble Drugs

DOI:

https://doi.org/10.37285/ijpsn.2015.8.3.2

Authors

  • Ganesh Raosaheb Godge
  • Shivanand Hiremath
  • Bhakti Sonawale
  • Rani Shirsath

Abstract

Cyclodextrins (CDs) are commonly used in drug formulations as solubility enhancers because of their ability to form water-soluble inclusion complexes with poorly water-soluble drugs. Cyclodextrins are useful molecular chelating agents. The cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. Orally administered drugs completely absorb only when they show fair solubility in gastric medium and such drugs shows good bioavailability. The solubility and dissolution properties of drugs play an important role in the process of formulation development. The most common pharmaceutical application of cyclodextrin is to enhance the solubility, stability, safety and bioavailability of drug molecules. Cyclodextrins are cyclic oligosaccharides which have recently been recognized as useful pharmaceutical excipients. As a result of molecular complexation phenomena CDs are widely used in many industrial products, technologies and analytical methods. The negligible cytotoxic effects of CDs are an important attribute in applications such as drug carrier, food and flavors, cosmetics, packing, textiles, separation processes, environment protection, fermentation and catalysis. The objective of this review is to discuss and summarize some of the findings and applications of cyclodextrin and their derivatives indifferent areas of drug delivery. The paper also highlights important CD application in drug solubility and dissolution, bioavailability, safety and stability, their use as excipients in drug formulation, design of various novel delivery systems like liposome, microspheres, microcapsules, and nanoparticles. 

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Keywords:

Cyclodextrins, bioavailability, dissolution, solubility, pharmaceutical excipients

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Published

2015-08-30

How to Cite

1.
Godge GR, Hiremath S, Sonawale B, Shirsath R. Pharmaceutical Advances in Cyclodextrin Inclusion Complexes for Improved Bioavailability of Poorly-Soluble Drugs. Scopus Indexed [Internet]. 2015 Aug. 30 [cited 2024 Dec. 10];8(3):2894-905. Available from: https://www.ijpsnonline.com/index.php/ijpsn/article/view/781

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Section

Review Articles

References

Arima, H, Yunomae K, Miyake K, Irie T, Hirayama F and Uekama K (2001). Comparative Studies of the Enhancing effects of Cyclodextrins on the Solubility and oral Bioavailability of Tacrolimus in Rats. J Pharm Sci. 90: 690-701.

Arima H and Uekama K (2007). Cyclodextrins and other Enhancers in Rectal Delivery. Enhancement in Drug Delivery. Edited by Touitou, Elka; Barry, Brian W. CRC Press: BocaRaton, Fla. 147-172.

Badawy SIF, Ghorab MM and Adeyeye CM (1996). Bioavailability of Danazol hydroxypropyl-β-cyclodextrin Complex by different Routes of Administration. Int J Pharm. 145: 137-143.

Becket G, Schep LJ and Tan MY (1999). Improvement of the in vitro Dissolution of Praziquantal by Complexation with alpha, beta and gamma-cyclodextrins. Int J Pharm. 179: 65-71.

Behl CR, Pimplaskar HK, Sileno AP, Demeireles J and Romeo VD (1998). Effects of Physicochemical properties and other factors on Systemic Nasal Drug Delivery. Adv Drug Del Rev. 29: 89-116.

Brewster ME, Loftsson T, Estes KS, Lin JL and Frioriksdottir H (1992). Effects of various Cyclodextrins on Solution Stability and Dissolution rate of Doxorubicin Hydrochloride. Int J Pharm. 79: 289-299.

Brown GA, Martin ER, Roberts BS, Vukovich MD and King DS (2002). Acute Hormonal response to Sublingual Androstenediol in Young men. J Appl Physiol. 92: 142-146. PMid:11744653.

Carrier RL, Miller LA and Ahmed I (2007). The utility of Cyclodextrins for Enhancing Oral Bioavailability. J Contr Rel. 123: 78-99.

Challa R, Ahuja A, Ali J and Khar R (2005). Cyclodextrin in Drug Delivery: an updated review. AAPS Pharm Sci Tech. 6: 329-357.

Croyle MA, Cheng X and Wilson JM (2001). Development of Formulations that Enhance Physical Stability of Viral vectors for Gene therapy. Gene Ther. 8: 1281-1290.

Godge G and Hiremath S (2014). Development and Evaluation of Colon Targeted Drug Delivery System by using Natural Polysaccharides/Polymers. Dhaka University Journal of Pharmaceutical Science . 13(1): 105-113.

Godge G and Hiremath S (2012). Colonic Delivery of Film Coated Meloxicam Tablets using Natural Polysaccharide Polymer Mixture. International Current Pharmaceutical Journal 1(9): 264-271.

Godge G and Hiremath S (2014). An Investigation into the Characteristics of Natural Polysaccharide: Polymer Metoprolol Succinate Tablets for Colonic Drug Delivery. Mahidol University Journal of Pharmaceutical Sciences. 41(2): 7-21.

Godge G and Hiremath S (2014). Colon Targeted Drug Delivery System: A Review. Int J Pharm Drug Analysis. 2(1): 3-9

Harrs D and Robinson JR (1992). Drug delivery via the Mucous Membranes of the oral cavity. J Pharm Sci . 82: 1-10.

Hiremath S and Godge G (2013). Preparation and in-vitro Evaluation of Inclusion Complexes of Nelfinavir with Chemically Modified β-cyclodextrins. Dhaka University Journal of Pharmaceutical Sciences. 11(2): 107-116.

Hoon TJ, Dawood MY, Khan-Dawood FS, Ramos J and Batenhorst RL (1993). Bioequivalence of 17 β-Estradiol Hydroxypropyl-β-Cyclodextrin Complex in Postmenopausal women. J Clin Pharmacol . 33: 1116-1121.

Irie T and Uekama K (1997). Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation. J Pharm Sci. 86: 147-62.

Kang J, Kumar V, Yang D, Chowdhury PR and Hohl RJ (2002). Cyclodextrin Complexation: Influence on the Solubility, Stability and Cytotoxicity of Camptothecin, Anantineoplastic agent. Eur J Pharm Sci. 15: 163-170.

Lantz A, Rodriguez M, Wetterer S and Armstrong D (2006). Estimation of Association Constants between oral Malodor Components and Various native and derivatized. cyclodextrins. Anal Chim Acta. 557: 184-190.

Li J, Guo Y and Zografi G (2002). The solid-state Stability of Amorphous Quinapril in the presence of βCD. J Pharm Sci. 91: 229-243.

Loftsson T, Brewster ME and Masson M (2004). Role of Cyclodextrins in Improving Oral Drug Delivery. Am J Drug Deliv. 2: 261-275.

Loftsson T and Stefansson E (1997). Effect of Cyclodextrins on Topical Drug Delivery to the Eye. Drug Dev Ind Pharm. 23: 473-481.

Loftsson T and Stefansson E (2007). Cyclodextrins in Ocular Drug Delivery: Theoretical basis with Dexamethasone as a Sample Drug. J Drug Del Sci Tech. 17: 3-9.

Loftsson T, Frithriksdóttir H, Stefánsson E, Thórisdóttir S, Guthmundsson O and Sigthórsson T (1994). Topically Effective Ocular Hypotensive Acetazolamide and Ethoxyzolamide Formu-lations in Rabbits. J Pharm Pharmacol . 46: 503-504.

Loftsson T, Sigurdsson HH, Hreinsdottir D, Konradsdottir F and Stefansson E (2007). Dexamethasone delivery to Posterior Segment of the Eye. J Inclusion Phenom Macrocyclic Chem 57: 585-589.

Loftsson T and Masson M (2001). Cyclodextrins in Topical Drug Formulations: Theory and practice. Int J Pharm. 225: 15-30.

Loftsson T, Vogensen S, Brewster ME and Konraosdottir F (2007). Effects of Cyclodextrins on Drug delivery through biological Membranes. J Pharm Sci. 10: 2532-2546.

Londhe V and Nagarsenker M (1999). Comparision between Hydroxypropyl-β-cyclodextrin and Polyvinyl Pyrrolidine as Carriers for Carbamazepine Solid Dispersions. Indian J Pharm Sci . 61: 237-240.

Lutka A and Koziara J (2000). Interaction of Trimeprazine with Cyclodextrins in Aqueous Solution. Acta Pol Pharm . 57: 369-374.

Lutka A (2002). Investigation of Interaction of Promethazine with Cyclodextrins in Aqueous Solution. Acta Pol Pharm. 59: 45-51.

Marttin E, Romeijn SG, Verhoef JC and Merkus FW (1997). Nasal Absorption of Dihydroergotamine from Liquid and Powder Formulations in Rabbits. J Pharm Sci. 86: 802-807.

Mannila J, Jarvinen T and Lehtonen M (2003). Effects of RM-α-CD on bioavailability of THC. Proceedings of the AAPS annual Meeting and Exposition. Salt Palace Convention Center, Salt Lake City, USA.

Merkus FW, Verhoef J, Romeijn SG and Schipper NG (1991). Absorption Enhancing Effect of Cyclodextrins in Itranasally Administered Insulin in rats. Pharm Res 8: 588-592.

Miyake K, Arima H and Hiramaya F (2000). Improvement of Solubility and oral bioavailability of Rutin by Complexation with 2-hydroxypropylbetacyclodextrin. Pharm Dev Technol 5: 399-407.

Nagase Y, Hirata M and Wada K (2001). Improvement of some Pharmaceutical Properties of DY-9760e by Sulfobutyl Ether Beta-Cyclodextrin. Int J Pharm 229: 163-172.

Nicolazzi C, Venard V, Le Faou A and Finance C (2002). In vitro Antiviral activity of the gancyclovir Complexed with beta Cyclodextrin on Human Cytomegalovirus strains. Antiviral Res. 54: 121-127.

Qian L, Guan Y and Xiao H (2008). Preparation and Characteri-zation of inclusion Complexes of a Cationic-β-cyclodextrin polymer with butylparaben or triclosan. Int J Pharm. 357: 244-251.

Rajewski RA and Stella VJ (1996). Pharmaceutical Applications of Cyclodextrins in vivo Drug Delivery. J Pharm Sci. 85: 1142-1168.

Sortino S, Giuffrida S and De Guldi G (2001). The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin: Dramatic effect of the Microenvironment on the Nature and on the efficiency of the Photo Degradation Pathways. Photochem Photobiol . 73: 6-13.

Suhonen P, Jarvinen T, Lehmussaari K, Reunamaki T and Urtti A (1995). Ocular Absorption and Irritation of Pilocarpine Prodrug is modified with Buffer, Polymer, and Cyclodextrin in the Eyedrop. Pharm Res. 12: 529-533.

Szejtli J (1982). Cyclodextrins and their Inclusion Complexes. Akademiai Kiado, Budapest.

Szente L, Szejtli J and Kis GL (1998). Spontaneous Opalescence of Aqueous β-cyclodextrin Solutions: Complex Formation or self-Aggregation. J Pharm Sci. 87: 778-781.

Tasic LM, Jovanovich MD and Djuric ZR (1992). The influence of beta-cyclodextrin on the Solubility and Dissolution rate of Paracetamol Solid Dispersions. J Pharm Pharmacol. 44: 52-55.

Thompson DO (1997). Cyclodextrins-enabling Excipients: Their present and future use in Pharmaceuticals. Crit Rev Ther Drug Carrier Syst. 14: 1-104.

Totterman AM, Schipper NG, Thompson DO and Mannermaa JP (1997). Intestinal safety of water-soluble _-cyclodextrins in Paediatric oral solutions of Spironolactone: effects on Human Intestinal Epithelial Caco-2cells. J Pharm Pharmacol 49: 43-8.

Uekama K (2004). Design and Evaluation of Cyclodextrin based Drug Formulation. Chem Pharm Bull. 8: 900-915.

Uekama K, Fujinaga T, Hirayama F, Otagiri M, Yamasaki M, Seo H, Hashimoto T and Tsuruoka M (1983). Improvement of the oral Bioavailability of Digitalis Glycosides by Cyclodextrin Complexation. J Pharm Sci. 72: 1338-1341.

Uekama K, Hirayama F and Irie T (1998). Cyclodextrin Drug Carrier Systems. Chem Rev. 98: 2045-2076.

Ueda H, Ou D, Endo T, Nagase H, Tomono K and Nagai T (1998). Evaluation of a Sulfobutyl Ether beta-cyclodextrin as a solubilizing/Stabilizing Agent for Several Drugs. Drug Dev Ind Pharm. 24: 863-867.

Uekama K and Otagiri M (1987). Drug Carrier System – A Review. Crit Rev Ther Drug Car Sys. 3: 1-12.

Uekama K, Ikegami K, Wang Z, Horiuchi Y and Hirayama F (1992). Inhibitory Effect of 2-hydroxypropyl-β-cyclodextrin on Crystal-Growth of Nifedipine during Storage: Superior Issolution and oral Bioavailability compared with Polyvinylpyrrolidone K-30. J Pharm Pharmacol. 44: 73-78.

Uekama K, Horiuchi Y, Kikuchi M and Hirayama F (1988). Enhanced Dissolution and oral bioavailability of α-tocopheryl esters by dimethyl-β-cyclodextrin complexation. J Incl Phenom. 6: 167-174.

Van Dorne H (1993). Interaction between Cyclodextrins and Ophthalmic Drugs. Eur J Pharm Biopharm. 39: 133-139.

Yoo SD, Yoon BM, Lee HS and Lee KC (1999). Increased Bioavailability of Clomipramine after Sublingual Administration in Rats. J Pharm Sci. 88: 1119-1121.