Pharmaceutical Studies of Levothyroxine Sodium Hydrate Suppository Provided as a Hospital Preparation

• Published in: Biological & pharmaceutical bulletin 2015/04/01, Vol.38(4), pp.625-628
• Main Authors: Hamada, Yuhei, Masuda, Kazushi, Okubo, Masato, Nakasa, Hiromitsu, Sekine, Yuko, Ishii, Itsuko
• Format: Article
• Language: English
• Subjects: Drug Compounding; Drug Liberation; Drug Stability; Drug Storage; hospital preparation; hypothyroidism; levothyroxine sodium hydrate; Light; pharmaceutical study; Pharmacy Service, Hospital; Suppositories; suppository; Temperature; thyroid gland hormone replacement therapy; Thyroxine - analysis; Thyroxine - chemistry; Triglycerides - chemistry
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00721

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital’s protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4°C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.