Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

New Technological Approach for Glycyrrethic Acid Oral and Topical Administration

Author(s): Cinzia Pagano*, Luana Perioli, Paola Calarco, Alessandro Di Michele, Maria C. Tiralti and Maurizio Ricci

Volume 26, Issue 6, 2020

Page: [664 - 674] Pages: 11

DOI: 10.2174/1381612826666191226112249

Price: $65

conference banner
Abstract

Background: 18β- glycyrrhetinic acid (Gly) is the major bioactive component of licorice roots and rhizomes of the Glycyrrhiza glabra species. It shows many activities such as antiviral, anti-inflammatory, antioxidant, antimicrobial, and antifungal, however, its use in the health field is very limited due to the low water solubility.

Methods: This paper deals with the development of a new technological approach for Gly dissolution rate enhancement. It consists of Gly intercalation (guest) in the interlamellar spaces between the inorganic spaces (host) of the anionic clays “hydrotalcites” (HTlc) to obtain hybrids MgAl-HTlc-Gly and ZnAl-HTlc-Gly. Gly can find applications in both systemic and local therapies, thus advantages of the use of the hybrids in these two fields were investigated.

Results: Gly dissolution rate from hybrids in the intestinal environment, site in which it is preferentially absorbed, resulted enhanced (ZnAl-HTlc-Gly > MgAl-HTlc-Gly) compared to the crystalline form, thereby, making them suitable for oral administration as dry powder in hard capsules.

For a local therapy, bioadhesive, vaginal emulgels loaded with the hybrids were developed. These showed suitable mucoadhesive property to the vaginal mucosa, necessary to prolong the residence time in the application site. The emulgel containing ZnAl-HTlc-Gly showed a faster and higher release profile than that containing MgAl- HTlc-Gly.

Conclusion: The obtained results suggest that Gly intercalation into HTlc, especially in ZnAl-HTlc, allows to enhance Gly dissolution when the hybrids are formulated both as oral or topical products.

Keywords: 18β- glycyrrhetinic acid, hydrotalcite, solubility, oral powder, vaginal emulgel, Gly intercalation.

« Previous Next »
[1]
Andersen FA. Cosmetic Ingredient Review Expert Panel. Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. Int J Toxicol 2007; 26(Suppl. 2): 79-112.
[http://dx.doi.org/10.1080/10915810701351228] [PMID: 17613133]
[2]
Mamedov NA, Egamberdieva D. Phytochemical constituents and pharmacological effects of licorice: a review plant hum heal. cham. Springer International Publishing 2019; Vol.3: 1-21.
[http://dx.doi.org/10.1007/978-3-030-04408-4_1]
[3]
Ming LJ, Yin ACY. Therapeutic effects of glycyrrhizic acid. Nat Prod Commun 2013; 8(3): 415-8.
[http://dx.doi.org/10.1177/1934578X1300800335] [PMID: 23678825]
[4]
Langer D, Czarczynska-Goslinska B, Goslinski T. Glycyrrhetinic acid and its derivatives in infectious diseases. Curr Issues Pharm Med Sci 2016; 29: 118-23.
[http://dx.doi.org/10.1515/cipms-2016-0024]
[5]
Yang R, Wang LQ, Yuan BC, Liu Y. The Pharmacological activities of licorice. Planta Med 2015; 81(18): 1654-69.
[http://dx.doi.org/10.1055/s-0035-1557893] [PMID: 26366756]
[6]
Oyama K, Kawada-Matsuo M, Oogai Y, Hayashi T, Nakamura N, Komatsuzawa H. Antibacterial effects of glycyrrhetinic acid and its derivatives on Staphylococcus aureus. PLoS One 2016; 11(11)e0165831
[http://dx.doi.org/10.1371/journal.pone.0165831] [PMID: 27820854]
[7]
de Breij A, Karnaoukh TG, Schrumpf J, et al. The licorice pentacyclic triterpenoid component 18β-glycyrrhetinic acid enhances the activity of antibiotics against strains of methicillin-resistant Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 2016; 35(4): 555-62.
[http://dx.doi.org/10.1007/s10096-015-2570-z] [PMID: 26780691]
[8]
Pellati D, Fiore C, Armanini D, Rassu M, Bertoloni G. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans. Phytother Res 2009; 23(4): 572-4.
[http://dx.doi.org/10.1002/ptr.2693] [PMID: 19067381]
[9]
Li G, Nikolic D, van Breemen RB. Identification and chemical standardization of licorice raw materials and dietary supplements using UHPLC-MS/MS. J Agric Food Chem 2016; 64(42): 8062-70.
[http://dx.doi.org/10.1021/acs.jafc.6b02954] [PMID: 27696846]
[10]
Nakamura T, Nishibu A, Yoshida N, et al. Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin-1. Exp Dermatol 2016; 25(4): 299-304.
[http://dx.doi.org/10.1111/exd.12931] [PMID: 26739065]
[11]
Barceloux DG. Medical toxicology of natural substances. Hoboken, NJ, USA: John Wiley & Sons, Inc. 2008.
[http://dx.doi.org/10.1002/9780470330319]
[12]
Shen Z, Qin Q, Liao X, Yang B. Host-guest inclusion system of glycyrrhetic acid with polyamine-β-cyclodextrin: preparation, characterization, and anticancer activity. J Mol Struct 2017; 1149: 155-61.
[http://dx.doi.org/10.1016/j.molstruc.2017.07.104]
[13]
Liang S, Li M, Yu X, et al. Synthesis and structure-activity relationship studies of water-soluble β-cyclodextrin-glycyrrhetinic acid conjugates as potential anti-influenza virus agents. Eur J Med Chem 2019; 166: 328-38.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.074] [PMID: 30731401]
[14]
Puglia C, Rizza L, Drechsler M, Bonina F. Nanoemulsions as vehicles for topical administration of glycyrrhetic acid: characterization and in vitro and in vivo evaluation. Drug Deliv 2010; 17(3): 123-9.
[http://dx.doi.org/10.3109/10717540903581679] [PMID: 20136625]
[15]
Sui X, Wei W, Yang L, et al. Preparation, characterization and in vivo assessment of the bioavailability of glycyrrhizic acid microparticles by supercritical anti-solvent process. Int J Pharm 2012; 423(2): 471-9.
[http://dx.doi.org/10.1016/j.ijpharm.2011.12.007] [PMID: 22183131]
[16]
Darvishi B, Manoochehri S, Kamalinia G, et al. Preparation and antibacterial activity evaluation of 18-β-glycyrrhetinic acid loaded PLGA nanoparticles. Iran J Pharm Res 2015; 14(2): 373-83.
[PMID: 25901144]
[17]
Tian Q, Wang W, He X, et al. Glycyrrhetinic acid-modified nanoparticles for drug delivery: preparation and characterization. Chin Sci Bull 2009; 54: 3121-6.
[http://dx.doi.org/10.1007/s11434-009-0249-5]
[18]
Feng R, Deng P, Song Z, et al. Glycyrrhetinic acid-modified PEG-PCL copolymeric micelles for the delivery of curcumin. React Funct Polym 2017; 111: 30-7.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2016.12.011]
[19]
Rives V, del Arco M, Martín C. Intercalation of drugs in layered double hydroxides and their controlled release: a review. Appl Clay Sci 2014; 88–89: 239-69.
[http://dx.doi.org/10.1016/j.clay.2013.12.002]
[20]
Perioli L, Ambrogi V, Nocchetti M, Sisani M, Pagano C. Preformulation studies on host-guest composites for oral administration of BCS class IV drugs: HTlc and furosemide. Appl Clay Sci 2011; 53: 696-703.
[http://dx.doi.org/10.1016/j.clay.2011.06.006]
[21]
Pagano C, Tiralti MC, Perioli L. Nanostructured hybrids for the improvement of folic acid biopharmaceutical properties. J Pharm Pharmacol 2016; 68(11): 1384-95.
[http://dx.doi.org/10.1111/jphp.12634] [PMID: 27734495]
[22]
Perioli L, Pagano C. Inorganic matrices: an answer to low drug solubility problem. Expert Opin Drug Deliv 2012; 9(12): 1559-72.
[http://dx.doi.org/10.1517/17425247.2012.733693] [PMID: 23061519]
[23]
Hydrotalcite BN. Resonance 2001; 6: 57-61.
[24]
Ballarin B, Mignani A, Mogavero F, Gabbanini S, Morigi M. Hybrid material based on ZnAl hydrotalcite and silver nanoparticles for deodorant formulation. Appl Clay Sci 2015; 114: 303-8.
[http://dx.doi.org/10.1016/j.clay.2015.06.014]
[25]
Li Y, Bi H, Zhou C. Effects of Mg: Al molar ratio on the rheology of aqueous suspensions containing cationic starch and Mg/Al-hydrotalcite-like compounds. Russ Chem Bull 2015; 64: 2422-6.
[http://dx.doi.org/10.1007/s11172-015-1172-3]
[26]
Perioli L, Pagano C, Nocchetti M, Latterini L. Development of smart semisolid formulations to enhance retinoic acid topical application. J Pharm Sci 2015; 104(11): 3904-12.
[http://dx.doi.org/10.1002/jps.24612] [PMID: 26280093]
[27]
Khurana IS, Kaur S, Kaur H, Khurana RK. Multifaceted role of clay minerals in pharmaceuticals. Future Sci OA 2015; 1(3): FSO6.
[http://dx.doi.org/10.4155/fso.15.6]
[28]
Pagano C, Ceccarini B, Ricci P. Development and characterization of new topical hydrogels based on alpha lipoic acid-hydrotalcite hybrids. Cosmetics 2019; 6: 35.
[http://dx.doi.org/10.3390/cosmetics6020035]
[29]
Pagano C, Perioli L, Blasi F, Bastianini M, Chiesi C, Cossignani L. Optimisation of phenol extraction from wine using layered double hydroxides and technological evaluation of the bioactive-rich powder. Int J Food Sci Technol 2017; 52: 2582-8.
[http://dx.doi.org/10.1111/ijfs.13544]
[30]
Costantino U, Marmottini F, Nocchetti M, Vivani R. New synthetic routes to hydrotalcite-like compounds - characterisation and properties of the obtained materials. Eur J Inorg Chem 1998; 1998: 1439-46.
[http://dx.doi.org/10.1002/(SICI)1099-0682(199810)1998:10<1439:AID-EJIC1439>3.0.CO;2-1]
[31]
Santamaria P. Nitrate in vegetables: toxicity, content, intake and EC regulation. J Sci Food Agric 2006; 86: 10-7.
[http://dx.doi.org/10.1002/jsfa.2351]
[32]
Lei Y, Kong Y, Sui H, Feng J, Zhu R, Wang W. Enhanced oral bioavailability of glycyrrhetinic acid via nanocrystal formulation. Drug Deliv Transl Res 2016; 6(5): 519-25.
[http://dx.doi.org/10.1007/s13346-016-0300-4] [PMID: 27206446]
[33]
Perioli L, D’Alba G, Pagano C. New oral solid dosage form for furosemide oral administration. Eur J Pharm Biopharm 2012; 80(3): 621-9.
[http://dx.doi.org/10.1016/j.ejpb.2011.12.011] [PMID: 22230797]
[34]
Pagano C, Marmottini F, Nocchetti M, Ramella D, Perioli L. Effects of different milling techniques on the layered double hydroxides final properties. Appl Clay Sci 2018; 151: 124-33.
[http://dx.doi.org/10.1016/j.clay.2017.10.030]
[35]
Akao T, Hayashi T, Kobashi K, et al. Intestinal bacterial hydrolysis is indispensable to absorption of 18 β-glycyrrhetic acid after oral administration of glycyrrhizin in rats. J Pharm Pharmacol 1994; 46(2): 135-7.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb03756.x] [PMID: 8021802]
[36]
Bauer BA. Licorice Glycirrhiza spp.Brinckmann JA, Wollschlaeger B, Eds The ABC Clinical Guide to Herbs. Austin, TX: American Botanical Council 2003; pp. 273-83.
[37]
Murray MT. Glycyrrhiza glabra (Licorice) Textb Nat Med. Elsevier 2013; 804-12.
[38]
Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review 2018; 18. e339-347
[http://dx.doi.org/10.1016/S1473-3099(18)30103-8]
[39]
Sherry L, Kean R, McKloud E, et al. Biofilms formed by isolates from recurrent vulvovaginal candidiasis patients are heterogeneous and insensitive to fluconazole. Antimicrob Agents Chemother 2017; 61(9): e01065-17.
[http://dx.doi.org/10.1128/AAC.01065-17] [PMID: 28696240]
[40]
de Oliveira JR, Vilela PDGF, de Oliveira FE, et al. Antifungal effect of plant extracts on Candida albicans biofilm on acrylic resin. Braz Dent Sci 2013; 16(3): 77-83.
[http://dx.doi.org/10.14295/bds.2013.v16i3.909]
[41]
Shokri J, Adibki K. Application of cellulose and cellulose derivatives in pharmaceutical industries In. Cellulose - Medical, Pharmaceutical and Electronic Applications, InTech 2013; pp. 47-66.
[http://dx.doi.org/10.5772/55178]
[42]
Keshavarz M, Kaffashi B. The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives. Pharm Dev Technol 2014; 19(8): 952-9.
[http://dx.doi.org/10.3109/10837450.2013.846371] [PMID: 24160773]
[43]
Roy S, Pal K, Anis A, Pramanik K, Prabhakar B. Polymers in mucoadhesive drug-delivery systems: a brief note. Des Monomers Polym 2009; 12: 483-95.
[http://dx.doi.org/10.1163/138577209X12478283327236]
[44]
Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 1987; 5: 37-42.
[http://dx.doi.org/10.1016/0168-3659(87)90035-6]
[45]
Bhaskar R, Murthy RSR, Miglani BD, Viswanathan K. Novel method to evaluate diffusion controlled release of drug from resinate. Int J Pharm 1986; 28: 59-66.
[http://dx.doi.org/10.1016/0378-5173(86)90147-X]

Rights & Permissions Print Cite
Article Metrics
20
1
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy