The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7 ± 12.9 to 423 ± 15.9 nm while zeta potential values varied from -21.7 ± 0.90 to -22.7 ± 0.85 mV. The loading capacity varied from 17.9 ± 1.21 to 34.1 ± 1.16%. DSC, FT-IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p < .05) in total cholesterol, triglyceride, LDL-C and increased level of beneficial HDL-C along with improvement in the associated liver steatosis as confirmed through photomicrographs of liver sections. In this study, we confirmed that complexation of AC with NS would be a viable approach for improving oral bioavailability and in vivo performance of AC.

Drugs with low aqueous solubility show limited oral bioavaibility and dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization is a promising technique used to improve the oral solubility and dissolution rate of the drugs and hence their oral bioavailability. In general pharmaceutical co-crystals improve the physical properties such as crystallinity, solubility, wettability and dissolution behaviors of the drug without altering its pharmacological activity. The aim of this study was to enhance the solubility, dissolution rate and limited oral bioavailability of glimepiride (GLM) by cocrystallization with different carboxylic acid co-formers. Different co-crystal formulations were successfully prepared by ultrasound assisted suspension co-crystallization technique and then suspected to solubility study to choose the best formula to complete the study. Co-crystal of glimepiride -oxalic acid was characterized by X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and then further evaluated for dissolution behavior. The result showed that co-crystal could increase solubility and dissolution rate of glimepiride. The results of XRPD, FTIR and DSC indicating the presence of a new crystalline phase and formation of cocrystal while the SEM micrograph revealed the definite shape with crystalline composition of co-crystal. In vivo bioavailability study in rats showed higher Cmax , longer t1/2 el and MRT0-∞ and increased AUC0-∞ of 2.66 fold compared to the plain GLM. Therefore, co-crystallization technique can be expected to represent a promising tool for enhanced delivery of glimepiride.