Development and Characterization of Omega-3 Tablets - a new administration form for omega-3

Omega-3 fatty acids are used in both nutraceuticals and pharmaceuticals in the form of triglycerides and ethyl esters. Administration forms available for omega-3 oil include bulk oil, soft gel capsules, emulsions and some powder compositions. However, the niche omega- 3 tablets have so far remained unexplored. In the present work direct compaction grade powders comprising omega-3 oil as triglycerides or ethyl esters were prepared utilizing ß-cyclodextrin as encapsulating agent. Powders with omega-3 oil load ranging from 10-40% (w/w) have been prepared by vacuum drying, freeze drying or spray granulation of aqueous mixtures of omega-3 oil and ß- cyclodextrin. Spray granulation proved to be the superior drying method for the preparation of compactible powders. Powder X-ray diffractograms of the powders and crushed tablets show evidence of formation of new crystalline phases not present in pure ß-cyclodextrin, indicating true complexation of ethyl ester and triglycerides. 1H NMR data confirmed presence of ethyl ester:ß-CD inclusion complexes. The compactibility of the powders was explored by the preparation of tablets containing 20-40% (w/w) omega-3 oil as triglycerides or ethyl esters. It was found that powders with up to 35% (w/w) triglyceride oil and 30% (w/w) ethyl ester oil, respectively, could be directly compressed to tablets of good quality. Recent years focus on the health benefits from omega-3 fatty acids has caused foundation for a diverse assortment of omega-3 supplements concerning quality. The discovery of a relatively extended sale of low quality products in several markets has resulted in an increased focus on essential properties of omega-3 products, like bioavailability of the omega-3 fatty acids from the formulation and oxidative stability through shelf-life. The present work demonstrates that direct compaction grade powders based on spray granulated triglyceride oil and ß-cyclodextrin, the corresponding tablet cores and coated tablets can be prepared with sufficiently low oxidation values to satisfy relevant monographs for omega-3 products, i.e. with initial totox values of the respective formulations < 10. Increasing levels of ascorbic acid in the formulation was correlated with lower totox values; however, the combination with EDTA as processing agent proved necessary to ensure sufficient oxidative stability of triglyceride powders. Spray granulating under nitrogen atmosphere contributed to significantly decreased totox levels in powders after eight months of storage at accelerated temperature (37oC), compared to spray granulation in air. In longterm stability studies, it was confirmed that coated triglyceride tablets remained at totox level < 10 after one year of storage at ambient temperature. The bioavailability of EPA and DHA from the triglyceride tablets comprising 30% (w/w) triglyceride oil was established. It was found that the bioavailability, measured as relative levels of EPA and DHA in serum, was comparable to soft-gel capsules. It was further observed that time for maximum concentration of EPA and DHA in serum was significantly shorter administered as tablets compared to as soft-gels