Role of clove oil in solvent exchange-induced doxycycline hyclate-loaded Eudragit RS in situ forming gel

Graphical Abstract

Doxycycline hyclate (DH) loaded Eudragit RS (ERS) ISG comprising clove oil (CO) could transform into matrix depot after exposure to the simulated crevicular fluid, minimize DH burst release with sustainable manner and inhibit against S. aureus, E. coli, S. mutans and P. gingivalis which this activity depended on the ratio of CO and N-methyl pyrrolidone (NMP).

Highlights

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  Role of clove oil (CO) in doxycycline hyclate (DH)-loaded Eudragit RS (ERS) in situ forming gel (ISG) was investigated.

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  CO could solubilize ERS and increase the viscosity of ISG and also minimize DH burst release with sustainable DH release.

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  ISGs comprising CO could expel through the 27-gauge needle and transform into matrix depot in simulated crevicular fluid.

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  Antimicrobial activities against all test bacterias were increased when increasing CO and N-methyl pyrrolidone (NMP) ratio.

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  DH-loaded ERS ISG comprising CO could be used as a local drug delivery system for periodontitis treatment.

Abstract

Solvent exchange induced in situ forming gel (ISG) is the promising drug delivery system for periodontitis treatment owing to the prospect of maintaining an effective high drug level in the gingival crevicular fluid. In the present study, the influence of clove oil (CO) on the characteristics of doxycycline hyclate (DH)-loaded ISG comprising Eudragit RS (ERS) was investigated including viscosity/rheology, syringeability, in vitro gel formation/drug release, matrix formation/solvent diffusion and antimicrobial activities. CO could dissolve ERS and increase the viscosity of ISG and its hydrophobicity could also retard the diffusion of solvent and hinder the drug diffusion; thus, the minimization of burst effect and sustained drug release were achieved effectively. All the prepared ISGs comprising CO could expel through the 27-gauge needle for administration by injection and transform into matrix depot after exposure to the simulated gingival crevicular fluid. The antimicrobial activities against Staphylococcus aureus, Escherichia coli, Streptococcus mutans and Porphyromonas gingivalis were increased when the ratio of CO and N-methyl pyrrolidone (NMP) was decreased from 1:1 to 1:10 owing to higher diffusion of DH except that for C. albicans was increased as CO amount was higher. Therefore, CO could minimize the burst while prolonging the drug release of DH-loaded ERS ISG for use as a local drug delivery system for periodontitis treatment.