Comparison of Doxycycline Hyclate Release from Beta-Cyclodextrin Based In Situ Forming Systems for Periodontal Pocket Targeting

Abstract:

The release behavior of doxycycline hyclate (DH) from beta-cyclodextrin (β-CD) in situ gels (ISG) and in situ microparticles (ISM) was investigated using dialysis tube method and direct contact method compared to that from DH solution. From dialysis tube method, DH released completely from solution within 8 h, while it released with more sustainable from ISM and ISG completely at 12 h and 28 h, respectively. The release pattern of them was similar when tested using direct contact method (released completely at 9 days). The DH release from dialysis tube method of all systems was a first order kinetic. DH release from ISM using direct contact method fitted well with a Higuchi’s equation. The dialysis tube method was suitable for determining formula factors affecting the drug release behavior. However, to simulate the pocket condition with contact area is limited, the drug release test with direct contact method was preferred than dialysis tube method.

• Periodical: Key Engineering Materials (Volume 859)
• Pages: 120-124
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.859.120
• Online since: August 2020
• Authors: Sarun Tuntarawongsa*, Jongjan Mahadlek, Nutdanai Lertsuphotvanit, Thawatchai Phaechamud
• Keywords: Beta-Cyclodextrin, In Situ Forming System, Non-Aqueous in Oil Emulsion, Release Behavior

References

[1] V. Deo, S. Ansari, S. Mandia, M. Bhongade, Therapeutic efficacy of subgingivally delivered doxycycline hyclate as an adjunct to non-surgical treatment of chronic periodontitis, J. Oral. Maxillofac. Res. 2 (2011) e3.

DOI: 10.5037/jomr.2011.2103

[2] M. Kouchak, In situ gelling systems for drug delivery, Jundishapur. J. Nat. Pharm. Prod. 9 (2014) e20126.

DOI: 10.17795/jjnpp-20126

[3] M. Parent, C. Nouvel, M. Koerber, A. Sapin, P. Maincent, A. Boudier, PLGA in situ implants formed by phase inversion: Critical physicochemical parameters to modulate drug release, J. Control. Release. 172 (2013) 292-304.

DOI: 10.1016/j.jconrel.2013.08.024

[4] W. Rungseevijitprapa, R. Bodmeier, Injectability of biodegradable in situ forming microparticle systems (ISM), Eur. J. Pharm. Sci. 36 (2009) 524-531.

DOI: 10.1016/j.ejps.2008.12.003

[5] V.B.D. Mohanty, N. Simharaju, M.A. Haque, C.K. Sahoo, A review on in situ gel: a novel drug delivery system, Int. J. Pharm. Sci. Rev. Res. 50 (2018) 175-181.

[6] C. Bode, H. Kranz, F. Siepmann, J. Siepmann, In-situ forming PLGA implants for intraocular dexamethasone delivery, Int. J. Pharm. 548 (2018) 337-348.

DOI: 10.1016/j.ijpharm.2018.07.013

[7] L.N. Turino, R.N. Mariano, S. Boimvaser, J.A. Luna, In situ-formed microparticles of PLGA from O/W emulsions stabilized with PVA: encapsulation and controlled release of progesterone, J. Pharm. Innov. 9 (2014) 132-140.

DOI: 10.1007/s12247-014-9180-7

[8] M. Parent, A. Boudier, J. Perrin, C. Vigneron, P. Maincent, N. Violle, et al., In situ microparticles loaded with s-nitrosoglutathione protect from stroke, PLoS One. 10 (2015) e0144659.

DOI: 10.1371/journal.pone.0144659

[9] X. Luan, R. Bodmeier, In situ forming microparticle system for controlled delivery of leuprolide acetate: Influence of the formulation and processing parameters, Eur. J. Pharm. Sci. 27 (2006) 143-149.

DOI: 10.1016/j.ejps.2005.09.002

[10] G. Tiwari, R. Tiwari, A.K. Rai, Cyclodextrins in delivery systems: applications, J. Pharm. Bioallied. Sci. 2 (2010) 72-79.

DOI: 10.4103/0975-7406.67003

[11] N. Lertsuphotvanit, P. Chaiya, T. Phaechamud, Matrix forming behavior of doxycycline hyclate-loaded beta-cyclodextrin in situ forming matrix and microparticle, Key Eng. Mater. 819 (2019) 221-226.

DOI: 10.4028/www.scientific.net/kem.819.221

[12] S. Tuntarawongsa, N. Lertsuphovanit, J. Mahadlek, T. Phaechamud, Transformation of beta-cyclodextrin loaded oil/oil emulsion into microparticle for drug delivery system, Thai J. Pharm. Sci. 42 (2018) 202-205.

[13] M.V.S. Varma, A.M. Kaushal, A. Garg, S. Garg, Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems, Am. J. Adv. Drug Deliv. 2 (2004) 43-57.

DOI: 10.2165/00137696-200402010-00003

[14] 5 - Mathematical models of drug release. in: M.L. Bruschi (Eds.), Strategies to modify the drug release from pharmaceutical systems, Woodhead Publishing, Cambridge, 2015, pp.63-86.

DOI: 10.1016/b978-0-08-100092-2.00005-9

[15] N.P. Lang, J. Lindhe, Clinical Periodontology and Implant Dentistry, 2 Volume Set. Wiley, (2015).

[16] T.A. Ahmed, H.M. Ibrahim, A.M. Samy, A. Kaseem, M.T. Nutan, M.D. Hussain. Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability. AAPS PharmSciTech. 15 (2014) 772–780.

DOI: 10.1208/s12249-014-0101-3

[17] Y. Fu, W.J. Kao, Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems, Expert. Opin. Drug. Deliv. 7 (2010) 429-444.

DOI: 10.1517/17425241003602259

[18] C.S. Amarachi, G. Onunkwo, I. Onyishi, Kinetics and mechanisms of drug release from swellable and non swellable matrices: a review, Res. J. Pharm., Biol. Chem. Sci. 4 (2013) 97-103.