Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Abstract

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and L-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:L-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50 rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.

Optimization of spray drying process for formulation of solid dispersion containing polypeptide-k powder through quality by design approach

“…On the other hand, a welldesigned drying protocol also helps in improving the interaction of poorly soluble drug with the inert carriers, which ultimately results in increased solubility and better flow property of the drug. The drying processes routinely used are: rotary evaporation, freeze drying and spray A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 drying. Amongst these, spray and freeze drying processes have shown better performance in terms of product yield and ease of scale up.…”

Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

“…This can be considered as the equilibrium solubility value also in the presence of the different formulation components, as SER has been previously found not to solubilize GBC when physically mixed with the drug [8]. It has been reported that ARG can solubilize GBC at a 1:0.5 molar ratio [25]. However, in the current study, the maximum concentrations of ARG in the donor cell were always less than 0.1% (m/V), and we have found that at concentrations less than 1% (m/V), ARG was not able to increase the equilibrium solubility of GBC (results not shown).…”

“…Amorphous GBC, coamorphous GBC-SER at a 1:1 molar ratio, GBC-l-arginine (ARG) at a 1:1 molar ratio and all these three combined with sodium lauryl sulphate (SLS) were processed by cryomilling and used as model formulations. ARG was combined with GBC as previously it has been observed to enhance GBC dissolution [25]. SLS was incorporated into the co-amorphous formulations, since it is known to act as an absorption enhancer in vivo by modulating the cellular tight junctions below its critical micelle concentration (CMC, i.e.…”

Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system

“…Various strategies have been employed with the aim of improving the solubility and dissolution properties of orally administered glyburide, among which cyclodextrin complexation proved to be especially useful to improve the dissolution profiles of glyburide due to the enhanced solubility and wettability through the formation of inclusion complexes (Cirri et al, 2009;Singh et al, 2012b). Nevertheless, at present, there are no oral bioavailability improvements of glyburide in comparison with commercial micronised tablets via cyclodextrin complexation stategies.…”