Article
  • Formulation Design of pH Adjusted Rebamipide Solid Dispersions for Improved Solubility

  • Byungkwan Moon*,#, Youngjun Son**,#, Seung Jae Kim**, Sunjae Park**, Won Kyung Kim**, Jeong Eun Song**, and Gilson Khang*, **, ***,†

  • *Department of PolymerNano Science & Technology, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea
    **Department of Bionanotechnology and Bio-Convergence Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea
    ***Polymer Materials Fusion Research Center, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea

  • 용해도 개선을 위한 pH가 조절된 레바미피드 고체분산체의 제형 설계

  • 문병관*,# · 손영준**,# · 김승재** · 박선재** · 김원경** · 송정은** · 강길선*, **, ***,†

  • *전북대학교 고분자나노공학과, **전북대학교 바이오나노융합공학과, ***전북대학교 고분자융합소재연구소

  • Reproduction, stored in a retrieval system, or transmitted in any form of any part of this publication is permitted only by written permission from the Polymer Society of Korea.

Abstract

Rebamipide is a drug mainly used for gastric protection. However, due to low solubility and bioavailability, it is classified as Biopharmaceutical Classification System IV. In this study, to improve the solubility and bioavailability of rebamipide, a solid dispersion was prepared by encapsulating the drug in HPMC, a hydrophilic polymer, using a spray drying method. In addition, the pH-dependent solubility of rebamipide was improved by adjusting the pH of the solid dispersion and adding various surfactants. Chemical changes in the drug were confirmed through Fourier transform infrared spectroscopy, morphological changes were confirmed through scanning electron microscopy and crystallinity and saturation of the drug were confirmed through differential scanning calorimetry and X-ray diffractometer. Lastly, the release behavior of the drug was confirmed through solubility evaluation of the solid dispersion and dissolution test of the formulation, confirming the possibility of developing a formulation with improved solubility.


레바미피드는 위장 보호 작용을 촉진하여 위궤양을 완화하는데 주로 사용되는 약물이다. 하지만 낮은 용해도 및 생체 이용률로 인해 생물약제학적 분류체계 IV로 분류된다. 본 연구에서는 레바미피드의 용해도 및 생체 이용율을 개선하기 위해서 분무건조법을 이용하여 약물을 친수성 고분자인 하이드록시프로필 메틸셀룰로오스(hydroxypropyl methylcellulose, HPMC)에 포접시켜 고체 분산체를 제조하였다. 또한, pH의존적인 레바미피드의 용해도를 개선하기 위해 고체 분산액의 pH를 조절하고 다양한 계면활성제를 첨가하였다. 제조된 약물의 화학적 구조 변화는 퓨리에변환 적외선 분광법을 통해 확인하였고, 주사전자현미경을 통해 상전환에 의한 형태학적 변화를 확인하고 시차 주사 열량법, X-선 회절 분석을 통해 약물의 결정성 및 포접여부를 확인하였다. 최종적으로 고체분산체의 가용화도 평가와 제형의 용출시험을 통해 약물의 방출 거동을 확인하여 용해도가 개선된 제형의 개발 가능성을 확인하였다.


Keywords: rebamipide, solid dispersion, solubilization, pH adjuster, surfactant.

  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2023 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2024; 48(3): 299-304

    Published online May 25, 2024

  • 10.7317/pk.2024.48.3.299
  • Received on Nov 30, 2023
  • Revised on Feb 23, 2024
  • Accepted on Mar 11, 2024

Correspondence to

  • Gilson Khang

  • *Department of PolymerNano Science & Technology, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea
    **Department of Bionanotechnology and Bio-Convergence Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea
    ***Polymer Materials Fusion Research Center, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Korea

  • E-mail: gskhang@jbnu.ac.kr