Stability of Betaine Capsules

Betaine is used to treat homocystinuria and is not available in Canada as a formulated drug. In order to facilitate the administration of this compound to patients, a capsule formulation and an evaluation of its stability were required. Capsule formulations of betaine were developed (160？mg and 625？mg of betaine per capsule). As betaine has no chromophore, an HPLC-ELSD analytical method was also developed. The critical quality attributes of these formulations were evaluated (content assay, content uniformity, and dissolution) as well as their stability. Capsules with acceptable quality attributes were produced. These capsules remained stable for 1 year when stored in airtight containers at controlled room temperature. However, shelf life decreased dramatically in nonairtight containers at 30°C (3 months for the lactose-containing capsules of 160？mg and 6 months for the capsules of 625？mg). 1. Introduction Homocystinuria is a metabolic disorder that appears in early childhood and is characterized by homocysteine excess in the blood stream. Symptoms of homocystinuria are multiple and include severe growth and bone impairments. Patients must have lifetime follow-ups by healthcare providers in order to keep their condition under control [1–4]. Betaine is used to treat homocystinuria and is commercialized as a white granulated powder that can be dissolved in 120 to 180？mL of water, juice or milk and administered immediately [1–5]. The dosage of betaine should be between 100 and 150？mg/kg/day in 2, 3, or 4 doses. The exact dose is calculated from the concentration of homocysteine in the blood. Betaine doses required to treat each patient must therefore be individualized [1]. Betaine in gelatin capsules facilitates administration by preventing patients from having to measure or weigh their medication. They can either swallow the capsule or open it and dissolve its content in the appropriate vehicle. Although betaine in capsule compounded formulations are prepared by hospital pharmacists in Canada, the stability of this preparation has not been previously reported. Betaine, also known as betaine oxyneurine, or trimethylglycine, is an inner salt formed from a quaternary ammonium and a carboxylate (Figure 1). This crystalline powder is very soluble in water (160？g/100？g of water) and is also hygroscopic [6]. Based on the chemical structure of this compound, chemical stability is not expected to be problematic under nonenzymatic conditions. However, a monohydrated form has been reported, and therefore solubility could be affected by changes in the solid phase [6].