Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with β-cyclodextrin

Abstract

The purpose of this study was to improve the solubility and dissolution rate of sulfamethoxazole (SMZ) with inclusion compound of β-cyclodextrin (β-CD). The interaction between SMZ and β-CD in solution was studied by the phase-solubility method. The phase-solubility studies revealed the formation of inclusion complexes with poor solubility with an inclusion complex of 1:1 molar ratio and a stability constant of 122.3 M(-1). The solid complexes of SMZ with β-CD were prepared by using kneading and coprecipitation methods. The physical mixture of these chemicals was also prepared for comparison. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycol 20000 and non-ionic surfactants i.e., polysorbate 20 on the complexation of SMZ with β-CD was also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. The formulation, that provided delivery of active material near to the target value in six healthy volunteers and in vivo tests, clearly revealed that the bioavailability of active material was found to be enhanced by preparing ternary mixtures.

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

“…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.…”

Miscibility of poly(acrylic acid)/poly(methyl vinyl ketone) blend and in vitro application as drug carrier system

“…Different researchers focused their investigations to enhance the solubility of this drug using different methods [63–65]. For example, the addition of β-cyclodextrin (β-CD) to the STX realized by Ozdemir et al [64] using the phase solubility method permitted to enhance a maximum solubility of 188 mg.L −1 at pH7 and 175 mg.L −1 at media pH4.5. These same investigators by adding of EG to the previous mixture obtained 406 and 377 mg.L −1 in media pH7 and 4.5, respectively.…”

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“…[66] Ozdemir and Erkin formulated the inclusion complexes of sulfamethoxazole with β-CD and in vivo studies on six healthy volunteers showed the higher bioavailability as compared to pure. [67] Holm et al studied the effect of cyclodextrin concentration on the oral bioavailability of danazol and cinnarizine in rats. Pharmacokinetic studies showed that bioavailability of danazol decreased with increase in the concentration of CD whereas there was no significant effect on bioavailability of cinnarizine with change in concentration of CD.…”

“…[76] The formation of inclusion complexes of catechin with β-CD s showed the higher storage stability and provided more protection against temperature, oxygen, and light. [51] Sulfamethoxazole β-CD Enhance bioavailability and dissolution rate [67] Eslicarbazepine acetate β-CD Faster onset of action and higher bioavailability [69] Polylactic acid β-CD Improve the thermal expansion stability [72] Chimonanthus praecox β-CD Enhancement of antioxidant activity and thermal stability [73] Famotidine Carboxymethyl β-CD Improvement of chemical stability, oral bioavailability, and bitter taste [75] Astaxanthin HP-β-CD Storage stability and antioxidant activity [76] Catechin β-CD Protection of antioxidants, higher storage stability against temperature, oxygen, and light [51] α-tocopherol β-CD Higher antioxidant activity and better UV-light stability.…”