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

Abstract

The levothyroxine sodium hydrate suppository (L-T 4 -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-T 4 ) 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-T 4 in the L-T 4 -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-T 4 -suppository were investigated. Suppositories containing 300 µg L-T 4 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-T 4 -suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T 4 -suppository was stored at 4°C and protected from light. The release rate of L-T 4 increased as pH increased. However, no L-T 4 was released below pH 7.2. The release rate of L-T 4 decreased as temperature decreased. These findings suggest that the low level of release of L-T 4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T 4 -suppository administration.

Successful Management of Hypothyroidism in Gastric Outlet Obstruction Using Levothyroxine Rectal Enemas: A Case Report

“…A study evaluating the efficacy and pharmacokinetics of LT4 in human subjects with hypothyroidism demonstrated that LT4 suppositories had lower bioavailability and efficacy compared to oral LT4, even though T4 levels can be maintained in patients with hypothyroidism by administering LT4 suppositories at approximately twice the oral dose [ 5 ]. The lower bioavailability of rectal LT4 compared to its oral counterpart has been attributed to the low level of release LT4 in the rectum [ 6 ]. The rectal route seemed appealing, but LT4 suppositories were also not available.…”

Levothyroxine: Conventional and Novel Drug Delivery Formulations

“…On the one hand, rectal pH impairs the absorption of LT4. Hamada et al demonstrated that although LT4 suppository content was uniform and stable over 90 days, its release rate correlated directly with rectal pH ( 259 ). A 240-minute in vitro experiment showed an ∼20% release at pH 8.2 and undetectable release at pH <7.2.…”

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

“…Several recent publications investigated the stability of levothyroxine, and the development of new formulations with better stability [6,[8][9][10][11][12][13][14][15][16][17][18][19]. The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets was studied by Gupta et al and reported in 1990 [20] and aimed towards the transformations that took place in a solid formulation containing LTSS along with excipients that act as a catalyst to decomposition of API, leading to a shorter shelf-life of the product than the one mentioned by the manufacturer.…”