Development and Optimization of Gastroretentive Floating Tablets of Carbimazole

Abstract

Carbimazole, is a prodrug which is converted to the active form, methimazole, after absorption, used in the treatment of hyperthyroidism. Methimazole, hence preventing thyroid peroxidase enzyme from iodinating and coupling the tyrosine residues on thyroglobulin, reducing the production of the thyroid hormones T3 and T4 (thryoxine). The onset of anti-thyroid effect is rapid but the onset of clinical effects on thyroid hormone levels in the blood is much slower. This is because the large store of pre-formed T3 and T4 in the thyroid gland and bound to thyroid binding globulin (99% bound) has to be depleted before any beneficial clinical effect occurs. In this research work, the gastroretentive floating tablets of carbimazole (300 mg) were formulated through direct compression method by employing Hydroxy Propyl Methyl Cellulose K4M as matrix forming polymer along with sodium bicarbonate and citric acid as gas generating agent, maize starch as floating enhancers, talc as glidant and magnesium stearate as a lubricant. The reported duration of antithyroid action for a single oral dose of carbimazole is only 6 - 8 hrs. The clinical daily dose is 15 - 60 mg twice a day with stability at pH 1.2 and as the pH increases, it becomes unstable and undergoes a degradation reaction. The optimization of carbimazole gastroretentive floating tablets is carried out by central composite design. The two factors are selected for the central composite design i.e., concentration of polymer (A) and concentration of sodium bicarbonate (B). The prepared optimized formulation of carbimazole gastroretentive floating tablets were evaluated for several precompression parameters viz., angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio as well post compression parameters i.e., drug content, hardness, friability, floating lag time, total floating time, buoyancy studies, swelling studies and in-vitro drug release characteristics. The in-vitro release studies of optimized gastroretentive floating tablets of carbimazole were carried out in 0.1 N HCl (pH 1.2) as dissolution media by using paddle apparatus at 50 RPM and 37 ℃ ± 0.5. The optimized formulation exhibited acceptable values of tested parameters and was found stable at room temperature.