Combination of β-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique

Abstract

In the present study, we prepared an inclusion complex of methotrexate (MTX) with β-cyclodextrin (β-CD) in order to decrease its photosensitivity and enhance its aqueous solubility. Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability. The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/β-CD was found to be of 1:7, and the water-solubility of MTX was increased in an average of 10-fold. The photostability studies showed that the MTX became stable on exposure to light. Construction of pseudoternary diagrams were investigated to prepare a MTX/β-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential. The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39.42 nm. In vitro drug release in different pH media showed that the release profile of MTX from the MTX/β-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile. Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/β-CD loaded SMEDDS form of 1.57-fold. We concluded that the β-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.

Formation of the Ternary Inclusion Complex of Limaprost with α- and β-Cyclodextrins in Aqueous Solution

“…The significant downfield shifts were observed for 17-20 carbons of the ω-chain as the α-CD concentration increased. In addition, as shown in Table 2(B), the shift changes of the ω-chain (C18, 19,20) in the binary PGF 2α /α-CD system were similar to those in the ternary PGF 2α /α-CD/β-CD system. This suggests that α-CD interacts preferentially with the ω-chain and the pre-existing β-CD does not significantly interfere with the interaction of α-CD with the ω-chain.…”

“…5A). When α-CD was added, the additional correlation peaks ap- peared between the ω-chain protons (H17, 18,19,20) of PGF 2α and the H3′ and H5′ protons of α-CD (Fig. 5B).…”

“…Because CDs form inclusion complexes by encapsulating other compounds into their hydrophobic cavity, natural and chemically modified CDs are widely used as pharmaceutical and food additives. Many studies of CD inclusion complex formations have been conducted to improve physicochemical properties of drugs, such as poor water solubility, [7][8][9][10] degradation upon heating [11][12][13][14][15] or by light irradiation, [16][17][18][19] and oxidation. 20) However, most of these studies have examined the effect of a single type of CD.…”

Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation

“…These systems are thermally more stable when compared to conventional complex systems, eg, solid dispersions and inclusion complexes, meaning that hydrogel microparticulate systems prevent rapid drug polymer decomplexation and rapid release and improve solubility to a greater extent while having weak interactions, eg, van der Waal forces and hydrogen bonding that promote fast dissociation and release of drug. 18 , 20 …”

Preparation, Characterization and Stability Studies of Solid Self Emulsifying Drug Delivery System of Nifedipine

“…The dissolution of each formulation was performed in triplicate times. The dissolution profile of stable formulations was prepared and compared with the dissolution profile of the pure drug [20,21].…”