Vol.:(0123456789) 1 3
Journal of Pharmaceutical Investigation
https://doi.org/10.1007/s40005-019-00430-6
ORIGINAL ARTICLE
Emerging role of polyethylene glycol on doxycycline hyclate-
incorporated Eudragit RS in situ forming gel for periodontitis
treatment
Wai Wai Lwin
1
· Napaphol Puyathorn
2
· Setthapong Senarat
2
· Jongjan Mahadlek
3
· Thawatchai Phaechamud
2
Received: 15 October 2018 / Accepted: 7 February 2019
© The Korean Society of Pharmaceutical Sciences and Technology 2019
Abstract
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 modifcation of a burst release for DH-loaded ISG. DH-loaded ISG system
comprising PEG 1500 exhibited the Newtonian fow 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 difused 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 signifcantly 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-incor-
porated 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.
Keywords In situ forming gel · Solid-like matrix · PEG 1500 · Eudragit RS · Doxycycline hyclate · Burst release
Online ISSN 2093-6214
Print ISSN 2093-5552
* Thawatchai Phaechamud
thawatchaienator@gmail.com; tphaechamud011@yahoo.com
Wai Wai Lwin
waiwailwinkyiphyusin@gmail.com
Napaphol Puyathorn
puyathorn_n@silpakorn.edu
Setthapong Senarat
senarat_s@silpakorn.edu
Jongjan Mahadlek
mahadlek_j@su.ac.th
1
Department of Pharmaceutics, University of Pharmacy,
Mandalay, Myanmar
2
Department of Pharmaceutical Technology, Faculty
of Pharmacy, Silpakorn University, Nakhon Pathom 73000,
Thailand
3
Pharmaceutical Intelligence Unit Prachote Plengwittaya,
Faculty of Pharmacy, Silpakorn University,
Nakhon Pathom 73000, Thailand