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

• Main Authors: Vijay Sharma, Kamla Pathak
• Format: Article
• Language: English
• Published: Elsevier 2016-10-01
• Series: Acta Pharmaceutica Sinica B
• Subjects: Liquisolid tablet; Powder solution technology; Curcumin; Hydrogen bond formation; Cytotoxicity; Gastric permeation; Bioavailability; Pharmacokinetics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211383515300630

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.