Background : The Belladonna alkaloids Atropine Sulfate and Hyoscyamine Sulfate have identical molecular formulas but different stereo configurations. Hyoscyamine sulfate is considered to possess greater anticholinergic activity because it is composed almost entirely of the levo isomer. Current official methods for the analysis of tablets containing one or both of these alkaloids do not include dissolution testing.

Method : In this proposed procedure , dissolution testing is carried out with USP Apparatus 2 (paddles) at a speed of 100 rpm using 500 mL of water at 37 C as dissolution medium. Analytical determinations were made by HPLC with a 7.5 cm long C18 column. The mobile phase is prepared as indicated ; 2.5 g of 1-octanesulfonic acid , sodium salt is dissolved in 1000 mL of water already containing 2.5 mL of phosphoric acid ; 500 mL of this solutions is mixed with 500 mL of methanol. Injection volume is 200 uL , detection by UV absorbance at 220 nm. Reference solutions of appropriate strength are prepared in water.

Results : For a sample of Atropine sulfate tablets labeled to contain 0.4 mg per unit , testing was done after 30 minutes. Average % dissolution for 6 tablets was 95.1. For a sample of extended release Hyoscyamine Sulfate tablets labeled to contain 0.375 mg per unit , testing was done after 1 , 3 , 6 and 8 hours.  Average % dissolution for 6 tablets were 23.6 after 1 hour , 42.8 after 3 hours , 75.4 after 6 hours and 85.1 after 8 hours. A similar testing scheme was used with a sample of Hyoscyamine Sulfate capsules labeled to contain 0.375 mg per unit. Average % dissolution for 6 capsules were 26.3 after 1 hour, 52.7 after 3 hours , 76.9 after 6 hours and 91.9 after 8 hours.

Conclusions : The proposed method appears to be very appropriate for dissolution testing of Atropine Sulfate and Hyoscyamine sulfate tablets . It is recommended that more products be tested.