Effect of Oily Ingredients and Solid Adsorbents on the Chemical Stability of a Solid Dosage Form of Lubiprostone

• Published in: Bulletin of the Korean Chemical Society Vol. 41; no. 2; pp. 156 - 161
• Main Authors: Kim, Hyung Tae, Won, Dong Han, Ho, Myoung Jin, Hwang, Hyung Don, Jang, Sun Woo, Kim, Min‐Soo, Kang, Myung Joo
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley‐VCH Verlag GmbH & Co. KGaA 01.02.2020; 대한화학회
• Subjects: liquid chromatography‐tandem mass spectrometry/tandem mass spectrometry; Lubiprostone; Oily ingredient; Porous carrier; Stability; 화학
• ISSN: 1229-5949; 0253-2964; 1229-5949
• DOI: 10.1002/bkcs.11940

Lubiprostone (LPT), a novel laxative, is commercially available as a soft gelatin capsule with oily ingredient, complementing its poor water‐solubility and oxygen‐labile property. In the present study, in order to address drawbacks associated with soft capsule formulations such as difficulty in process control or high production costs, conversion of the drug‐loaded oil solution into powder dosage form was attempted using several oily ingredients and porous solid carriers. Drug solubilization in medium chain triglycerides (MCT) drastically improved the drug stability compared to that in powder or other oily ingredients, exhibiting over 95% of the drug remaining after 5 days of storage at 60 °C. However, conversion of drug‐loaded MCT into a free‐flowing powder using porous carriers markedly deteriorated drug stability. Although the drug stability in the solidified formulations prepared using Avicel PH 102 or Aerosil 200 were relatively higher than those prepared using metallic adsorbents (Florite, DCP A/T, and Neusilin US2), they were less stable than in the intact oil solution under stress and accelerated condition. This implied that the decreased thickness of the oily barrier in the solidified formula failed to inhibit the exposure of the labile compound to oxygen and/or moisture, thereby accelerating drug degradation. In vitro drug release from the adsorbent progressed rapidly, providing complete drug release within 15 min, under sink condition. This study suggests that the kind of oily vehicle and the thickness of the barrier are important factors for ensuring the stability of LPT, an oxygen‐labile compound, and additional pharmaceutical approaches are required for the construction of stable solid preparations. Effect of pharmaceutical excipients on chemical stability of lubiprostone.