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

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.

Physicochemical properties of ß-cyclodextrin solutions and precipitates prepared from injectable vehicles.

ß-Cyclodextrin (ß-CyD) is cyclic oligosaccharide of a glucopyranose, containing a relatively hydrophobic central cavity and hydrophilic outer surface. However, the usefulness of ß-CyD is limited owing to its low aqueous solubility whereas we found that its apparent high solubility was evident in some injectable solvents including 2-pyrrolidone (PYR), N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). Therefore, in the present study, the physicochemical properties of the 30-60% w/w ß-CyD in PYR, NMP and DMSO were investigated such as viscosity, water resistant, matrix formation rate and syringeability. The higher the concentration of ß-CyD resulted in the increased viscosity and the higher force and energy of syringeability. ß-CyD in PYR gave the highest viscosity which contributed to the lowest syringeability while ß-CyD in DMSO exhibited the highest syringeability. The ß-CyD in DMSO and NMP exhibited the higher rate of matrix formation. ß-CyD in PYR showed the highest water resistant for phase separation while ß-CyD in NMP gave the faster de-mixing rate compared to that from PYR. The difference in physicochemical properties of ß-CyD dried ppts studied by scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) revealed that there was partial complexation of ß-CyD with respective solvents. Both solution and precipitate characteristic properties will be useful for using ß-CyD in further investigation as matrix material dissolved in the injectable vehicles as the in situ forming gel for periodontitis treatment.