Effect of hydrogen bond formation/replacement on solubility characteristics, gastric permeation and pharmacokinetics of curcumin by application of powder solution technology

Abstract

The present research aimed to improve the dissolution rate and bioavailability of curcumin using the potential of liquisolid technology. Twelve drug-loaded liquisolid systems (LS-1 to LS-12) were prepared using different vehicles (PEG 200, PEG 400 and Tween 80) and curcumin concentrations in vehicle (40%, 50%, 60% and 70%, w/w). The carrier [microcrystalline cellulose (MCC) PH102] to coat (Aerosil®) ratio was 20 in all formulations. The systems were screened for pre-compression properties before being compressed to liquisolid tablets (LT-1 to LT-12). Post compression tests and in vitro dissolution of LTs were conducted and the results compared with those obtained for a directly compressed tablet (DCT) made of curcumin, MCC PH102 and Aerosil®. LTs exhibited higher cumulative drug release (CDR) than the DCT and the optimum formulation, LT-9 (made using Tween 80), was studied by powder XRD, DSC, SEM and FTIR. Ex-vivo permeation of curcumin from LT-9 through goat gastrointestinal mucosa was significantly (P<0.05) enhanced and its oral bioavailability was increased 18.6-fold in New Zealand rabbits. In vitro cytotoxicity (IC50) of LT-9 towards NCL 87 cancer cells was 40.2 µmol/L substantiating its anticancer efficacy. Accelerated stability studies revealed insignificant effects of temperature and humidity on LT-9. In summary, solubility enhancement of curcumin in LTs produced significant improvements in its permeation and bioavailability.

Critical parameters dictating efficiency of membrane-mediated drug transfer using nanoparticles

“…(81.7 ± 6.7, 0.0005 ± 0.0003 and 2.44 ± 0.24 mg/ml, respectively), Supplementary Table 1. This could be attributed to the hydrogen bonding between the methoxy groups of PEG of T80 and the hydroxyl moieties of curcumin (Sharma and Pathak, 2016). To confirm this, the solubility of curcumin in PEG600 solvent was compared to that in triolein or monoolein.…”

Investigating Gastroprotective Potential of Liquisolid Curcumin against the Role of Endogenous Aggressive Factors and Oxidative Stress Markers

“…LSC with higher solubility than curcumin affected higher dissolution of the active and hence superior therapeutic efficacy. 16 The mucoprotective potential of LSC over is an indicative of amelioration. Curcumin also accelerates the ulcer healing phenomenon by inhibiting gastric acid secretion and anti-inflammatory activity preventing inducible TNF-α production at post-transcriptional level and affecting oxidative stress along with total antioxidant capacity, as well as by inhibiting IL-6 secretion and preventing apoptosis.…”

“…Obtained product was termed as Liquisolid Curcumin (LSC). All the LSC were subjected to pre and post compression studies 16 and the optimized liquisolid formulation was selected to be screened for its gastroprotective potential.…”

“…In vitro cytotoxicity against NCL 87 cancer cells substantiated its anticancer efficacy. 16 In continuation with the encouraging results, the present study was undertaken to comparatively investigate the antiulcer effect of optimized Liquisolid Curcumin (LSC) formulation against curcumin in ethanol induced gastric damage model. Additionally, the ulceroprotective activity was also assessed biochemically by monitoring various oxidative stress markers in Wistar rats.…”

Attempts and outcomes of liquisolid technology: An updated chronological compilation of innovative ideas and adjuvants in the field

“…Thus the process of dissolution can be attributed to the above discussed three mechanisms -(a) movement of dissolution media through pores of the carrier material, (b) movement of dissolution media by solubilisation of carrier material towards the core, and (c) dissolution/diffusion/transfer of dissolved drug molecules in the bulk (42). According to Sharma & Pathak the increment in drug concentration in liquid portion resulted in amount of drug beyond the solubility limit, thus by decreasing the fraction of dissolved drug in non-volatile solvent the release rate decreases (43). Interestingly, a remarkable difference in dissolution behavior of drug from liquisolid formulation was observed when compared to the saturation solubility of drug in nonvolatile solvents alone.…”