Emerging role of polyethylene glycol on doxycycline hyclate-incorporated Eudragit RS in situ forming gel for periodontitis treatment

  • Wai Wai Lwin
  • Napaphol Puyathorn
  • Setthapong Senarat
  • Jongjan Mahadlek
  • Thawatchai PhaechamudEmail author
Original Article


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.

Graphical abstract

PEG loading into solvent induced ERS in situ forming gel for doxycycline hyclate periodontal pocket delivery.


In situ forming gel Solid-like matrix PEG 1500 Eudragit RS Doxycycline hyclate Burst release 



This research work was supported by the Research and Development Institute, Silpakorn University (Grant no. SURDI 57/01/42). This research work was also facilitated by the Faculty of Pharmacy, Silpakorn University, Thailand. We also would like to thank Anthony Phonpituck for valuable comments and help.

Compliance with ethical standards

Conflict of interest

Authors declare that there is no conflict of interest regarding the publication of this article.

Statement of human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  • Wai Wai Lwin
    • 1
  • Napaphol Puyathorn
    • 2
  • Setthapong Senarat
    • 2
  • Jongjan Mahadlek
    • 3
  • Thawatchai Phaechamud
    • 2
    Email author
  1. 1.Department of PharmaceuticsUniversity of PharmacyMandalayMyanmar
  2. 2.Department of Pharmaceutical Technology, Faculty of PharmacySilpakorn UniversityNakhon PathomThailand
  3. 3.Pharmaceutical Intelligence Unit Prachote Plengwittaya, Faculty of PharmacySilpakorn UniversityNakhon PathomThailand

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