Absorption of Vitamin K2 by Dogs after Oral Administration of a Soft Gelatin Capsule Formulation Containing a New Emulsion-type Vehicle

• Published in: Journal of pharmacy and pharmacology 1999-12, Vol.51 (12), p.1375-1380
• Main Authors: AMEMIYA, TOHRU, MIZUNO, SATOSHI, HAYASHI, YAYOI, YUASA, HIROAKI, WATANABE, JUN
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Cetomacrogol; Dogs; Emulsions; General and cellular metabolism. Vitamins; Intestinal Absorption; Male; Medical sciences; Microspheres; Pharmaceutical Vehicles; Pharmacology. Drug treatments; Surface-Active Agents; Vitamin K - administration & dosage; Vitamin K - blood; Vitamin K - pharmacokinetics
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357991777191

This study has evaluated the performance of a newly developed vehicle for administration of a drug in a soft gelatin capsule. The absorption of vitamin K2 in dogs after oral administration of the vitamin in a soft gelatin capsule containing the newly developed vehicle was compared with absorption after administration of a control formulation prepared by encapsulating the contents of a commercially available vitamin K2 capsule (Glakay capsules 15 mg) in the same type of soft gelatin. Under non‐fasted conditions the profile of the plasma concentration of vitamin K2 against time for the test formulation was comparable with that for the control formulation in non‐fasted dogs. Under fasted conditions, however, both the maximum concentration (Cmax) and the area under the plot of concentration against time (AUC) were significantly smaller for the test formulation than for the control formulation. The Cmax and AUC for the test formulation were about 10 times larger for non‐fasted dogs than for fasted dogs whereas values for the control formulation were about twice as large. These results suggest that both formulations might require the presence of food or digestive fluid components, or both, for better absorption of vitamin K2. It seems that although the performances of the test and control formulations were comparable in the presence of these components, the control formulation works better in their absence. It should be also noted that, in contrast with the results from the absorption tests, the dispersibility of the test vehicle in water was much better than that of the control vehicle. This suggests that dispersibility does not significantly affect vitamin K2 absorption. In conclusion, although the new vehicle did not perform better than the control vehicle in terms of vitamin K2 absorption, the performance of the control formulation was comparable for non‐fasted dogs. Because the new vehicle contains considerably less surfactant than the vehicles currently used in soft gelatin capsules, it could be a safer alternative for use under non‐fasted conditions.