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Thawatchai Phaechamud,Jongjan Mahadlek,Sarun Tuntarawongsa 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.4
Antibiotic-loaded in situ forming gels are particularly attractive for periodontitis treatment. They are in a sol form and gradually alter to a solid-like depot after administration into a periodontal pocket to deliver and maintain the effective high level of drug in the gingival crevicular fluid. Solvent-inducing in situ forming gel mostly exhibits the burst drug release owing to rapid diffusion of solvent. This study incorporated peppermint oil to modulate the drug release and the gel characteristics of doxycycline hyclate-loaded Eudragit RS in situ forming gel systems. Peppermint oil increased the viscosity and syringeability of the Eudragit RS solution comprising NMP as solvent and retarded the water penetration. Therefore the diminishment of burst liberation and the prolongation of drug release with an addition of peppermint oil were attained with concentration dependence mainly following Fickian diffusion mechanism. The drug release from the membrane-less diffusion method was apparently slower than that from the dialysis method because the rapid phase separation into solid-like matrix through a direct contact with dissolution medium generated a hard surrounding shell. These solvent exchange-inducing in situ forming gels comprising peppermint oil effectively inhibited Staphylococcus aureus, Escherichia coli, Streptococcus mutans and Porphyrommonas gingivalis; therefore, they exhibited the potential use as localized delivery systems for periodontitis treatment.
Wai Wai Lwin,Napaphol Puyathorn,Setthapong Senarat,Jongjan Mahadlek,Thawatchai Phaechamud 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.1
Phase separation with solvent exchange induced-in situ forming gel (ISG) is an attractive delivery system for periodontitis treatment. Eudragit ® RS-PO (ERS) in N-methyl pyrrolidone (NMP) was used as polymer matrix for doxycycline hyclate (DH)-loaded solvent-exchanged ISG; however, a high burst drug release was evident. The present study revealed the role of PEG 1500 on physicochemical properties and modification of a burst release for DH-loaded ISG. DH-loaded ISG system comprising PEG 1500 exhibited the Newtonian flow with acceptable injectability with PEG 1500 concentration dependence and high in vitro degradation owing to NMP and PEG 1500 liberation. Solvent exchange between NMP with PBS pH 6.8 conveyed the rapid phase separation of ERS/PEG 1500 as a matrix which the entrapped DH diffused out gradually. Both dialysis membrane and membrane-less methods proved the slower drug release of DH-loaded ERS ISG comprising PEG than PEG 1500-free ISG. SEM revealed the porous matrix topography from polymeric phase separation especially for higher PEG 1500 loading. PEG 1500 incorporation significantly decreased the inhibition diameter against S. aureus, E. coli and S. mutans (P < 0.05) indicating the retardation of drug release owing to the high viscosity of the PEG 1500. PEG 1500-incorporated DH-loaded ERS ISG exhibited the potential use for periodontitis treatment.