Stability of Oral Suspensions of Ursodiol Made From Tablets
Ursodiol (ursodeoxycholic acid) is a nontoxic, naturally occurring bile acid that constitutes 1-2% of human bile. It suppresses hepatic synthesis of cholesterol and aids in the desaturation of biliary cholesterol and dissolution of cholesterol gallstones. Ursodiol is indicated for the treatment of primary biliary cirrhosis and cholesterol gallstones in patients who cannot or will not undergo cholecystectomy. It is also used to treat many other hepatobiliary disorders.

FDA-approved package labeling does not include an indication for ursodiol use in children, but such use has been described in the treatment of cholestasis associated with cystic fibrosis, total parenteral nutrition, Alagille syndrome, Byler disease, and biliary atresia. Defective bile acid elimination may be responsible for the cholestasis associated with these disorders, causing accumulation of toxic bile acids in the liver, systemic circulation, and peripheral tissues. Ursodiol dissolves in the small intestine and is delivered to hepatocytes in portal blood where it displaces the toxic bile acids, protecting the liver and promoting bile flow. The recommended dosage in pediatric patients with primary biliary cirrhosis ranges from 15 to 30 mg/kg given once daily.

There are two commercial formulations of ursodiol available: a 300- mg capsule and a 250-mg tablet. However, no commercially available liquid preparations of ursodiol exist for patients who are unable to take tablets and capsules. Two reports about the stability of extemporaneously compounded liquid preparations of ursodiol have been published. High-performance liquid chromatography (HPLC) analysis of a 60-mg/mL formulation performed by Johnson and Nesbitt showed that the preparation was stable for 35 days while refrigerated, and a 25-mg/ mL formulation studied by Mallett et al. was stable for 60 days at room temperature or while refrigerated. Both preparations were formulated with the 300-mg ursodiol capsule. Although there are currently no published reports describing the stability of a sugar-free oral liquid formulation of ursodiol, this product would be beneficial for children receiving a ketogenic, diabetic, or oral liquid diet or having other dietary restrictions. The purpose of this study was to prepare an oral liquid formulation of ursodiol from commercially available tablets in both syrup and a sugar-free vehicle and to determine the shortterm stability of these formulations over a 90-day period.