INDSTRIALIZATION OF CHEWABLE SUGAR COATED TABLETS OF PHYTOMENADIONE- Î’ CYYCLODEXTRIN COMPLEXS

Abstract

Vitamin k1 (phytomenadione) is a procoagulant factor, used in cases of hemorrhage or risk of hemorrhage. Being a component of hepatic carboxylase system, phytomenadione is involved in carboxylation of clotting factors II (prothrombin), VII, IX and X, and of clotting inhibitors protein C and protein S in the postribosomal phase. Yet, orally ingested phytomenadione is absorbed primarily in the middle portions of the small intestine. Moreover, optimum absorption is possible only in the presence of bile and pancreatic juice. Thus, Systemic availability after oral dosing is only approximately 50%, with large interindividual differences due to its limited aqueous solubility. Since aqueous solubility of a drug could be regarded as a key factor responsible for low oral bioavailability of poor water soluble drugs, thereby limiting their therapeutic potential. Consequently, the rationale of this study was to improve the biological performance of Phytomenadione by forming inclusion complexes with β cyclodextrin to enhance its solubility, dissolution rate, and stability. Furthermore, to enhance the solubilization power of the complexation, it was investigated in the presence and absence of PEG 4000 and 6000 as water soluble polymers and the formed binary and ternary systems were then incorporated into chewable sugar coated tablets (CSCT). Stability studies were performed on the prepared CSCT to confirm the enhancement of chemical stability. The best chosen formula was manufactured and distributed by Nile Company under the proprietary name of Vitadione.