Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

Abstract

Abstract. The aims of this study were to enhance the solubility and dissolution rate of nimodipine (ND) by preparing the inclusion complexes of ND with sulfobutylether-b-cyclodextrin (SBE-β-CD) and 2-hydroxypropyl-b-cyclodextrin (HP-β-CD) and to study the effect of the preparation method on the in vitro dissolution profile in different media (0.1 N HCl pH 1.2, phosphate buffer pH 7.4, and distilled water). Thus, the inclusion complexes were prepared by kneading, coprecipitation, and freeze-drying methods. Phase solubility studies were conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were investigated with differential scanning calorimetry (DSC), Xray diffractometry (X-RD), and Fourier transform infrared spectroscopy (FT-IR). Stable complexes of ND/SBE-β-CD and ND/HP-β-CD were formed in distilled water in a 1:1 stoichiometric inclusion complex as indicated by an A L -type diagram. The apparent stability constants (Ks) were 1334.4 and 464.1 M −1 for ND/SBE-β-CD and ND/HP-β-CD, respectively. The water-solubility of ND was significantly increased in an average of 22-and 8-fold for SBE-β-CD and HP-β-CD, respectively. DSC results showed the formation of true inclusion complexes between the drug and both SBE-β-CD and HP-β-CD prepared by the kneading method. In contrast, crystalline drug was detectable in all other products. The dissolution studies showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products.

Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

“…The presence of the butyl chain coupled with the repulsion of the negatively charged end group allows for an “extension” of the hydrophobic region of CD cavity. [ 40 ] De Chasteigner et al . findings in the year 1996 suggest that longer the hydrophobic chain linked to β-CD, the higher the association of drug within the complex.…”

“…findings in the year 1996 suggest that longer the hydrophobic chain linked to β-CD, the higher the association of drug within the complex. [ 40 41 ] Elbary et al . also observed solubility plots of AL type with solubility enhancing the potential of CDs decreasing in the order DMBCD > HPBCD > BCD and solubility constants of 567, 464.92 and 381.44 M −1 respectively.…”

Solubility enhancement of nimodipine through preparation of Soluplus® dispersions

“…4) showed many main peaks at; 3,297 cm −1 due to N-H stretching, 3,097 cm −1 due to C-H aromatic stretching, 2,933 cm −1 due to C-H aliphatic stretching, 1,695 cm −1 due to C = O stretching in ester, 1,648 cm −1 due to C = C stretching, 1,621 cm −1 due to C = C aromatic, 1,523 cm −1 due to −NO 2 , 1,381 cm −1 due to −C-CH 3 , and 1,134 cm −1 that can be related to −C-O-ester. All these bands were assigned as the fingerprints of nimodipine in the literature (Semcheddine et al, 2015).…”

Validation of a New RP-HPLC Method for Determination of Hydrocortisone Acetate Complexed with HPβCD in a Oral Liquid Pharmaceutical Preparation

“…CDs are capable of forming inclusion complexes with various types of lipophilic drugs with improve solubility, stability or other physicochemical properties [8]. Complexation of molecules to CDs occurs through a non-covalent interaction between the molecule and the CDs cavity [9].…”