期刊
JOURNAL OF PHARMACEUTICAL INVESTIGATION
卷 50, 期 1, 页码 81-94出版社
SPRINGERNATURE
DOI: 10.1007/s40005-019-00430-6
关键词
In situ forming gel; Solid-like matrix; PEG 1500; Eudragit RS; Doxycycline hyclate; Burst release
资金
- Research and Development Institute, Silpakorn University [SURDI 57/01/42]
Phase separation with solvent exchange induced-in situ forming gel (ISG) is an attractive delivery system for periodontitis treatment. Eudragit (R) 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. Graphical abstract PEG loading into solvent induced ERS in situ forming gel for doxycycline hyclate periodontal pocket delivery. [GRAPHICS] .
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