| Summary: | Vitamin D3 (cholecalciferol) (Vit D3) is a form of vitamin D (Vit D) that is essential for normal body function in humans. Vit D is a fat-soluble vitamin used to prevent osteoporosis in adults, prevent rickets in children, and supplement Vit D deficiencies which are seen worldwide. Physicians usually recommend 2,000 International Units (IU) Vit D3 for these deficiencies, but due to the poor aqueous solubility of Vit D3, this dose can be insufficient for patients. It would be more beneficial to recommend 5,000 IU. In 1994, the Dietary Supplement Health and Education Act was passed defining vitamins as “dietary supplements” and no longer required FDA registration prior to marketing. Dissolution results are expressed as the percent of the content released into solution, with a target of 85 to 125%. There is not an effective dissolution test existing for Vit D3 product evaluation, so an optimized dissolution test for Vit D3 was developed and used to evaluate non-prescription Vit D3 products. The current FDA guideline for Vit D3 dissolution is USP Apparatus II with 500 mL of 0.3% sodium dodecyl sulfate (SDS) in water. Since Vit D3 is not very water soluble, a surfactant is required for it to go into solution. The research was started with a larger volume (1 L) and with commonly used pharmaceutical grade surfactants: Triton X-100, Tween 80, Span 20, and sodium lauryl sulfate (SLS). SDS was eliminated due to interference with the HPLC analysis. Using two Vit D3 test products, which previous research found to have consistent drug content, each of these surfactants were tested at 0.8%. After evaluating the HPLC results, Triton and Tween were eliminated due to too much interference with the analysis process. The interference consisted of a large initial solvent front peak, elevated baseline, overlap with the drug peak, and required significant decrease in the mobile phase flow rate. Changing the mobile phase to 50/50 methanol/1-propanol solved the flow rate issue and peak separation overlap, but not the large solvent peak or elevated baseline. Dissolution testing continued using SLS and Span using 0.6%. Dissolution of the two test products, designated A and B, with 2 representing 2000 IU and 5 being 5000 IU, yielded higher values using SLS (A2 75.5%; A5 152.8%; B2 30.9%; B5 36.6%) compared to Span (A2 15%; A5 136%; B2 20.3%; B5 63%). Additional work continued to determine the best concentration of SLS. Better dissolution results were obtained using 1.2% (A2 88.1%; A5 156.7%) when compared to 0.3% (A2 87.4%; A5 153.2%), 0.6% (A2 70.7%; A5 132.2%), and 0.9% (A2 79.7%; A5 150.5%). Use of 1.5% did not yield a significant improvement (A2 84% vs 86.8%; A5 146.4% vs 144.6%), so 1.2% was chosen as this would minimize the amount of surfactant in the samples. The final dissolution method was created using a USP Apparatus II in 1000 mL containing 1.2% SLS in water. Based upon these characteristics, SLS 1.2% gave a good balance of minimizing surfactant concentration and analytical interference while maximizing Vit D3 dissolution.
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