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

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%,/). 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 anddissolution 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.permeation of curcumin from LT-9 through goat gastrointestinal mucosa was significantly (<0.05) enhanced and its oral bioavailability was increased 18.6-fold in New Zealand rabbits.cytotoxicity (IC) 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.

Norfloxacin loaded pH triggered nanoparticulate in situ gel for extraocular bacterial infections: Optimization, ocular irritancy and corneal toxicity

In order to achieve prolong corneal contact time of norfloxacin[NFX] for treatment of extra ocular diseases, a pH triggered nanoparticulate in situ gelling system was designed to explore dual advantage of nanoparticles and in situ gelling system, for its ocular delivery. NFX loaded nanocarriers were developed by ionotropic gelation technique using chitosan as a matrix forming polymer, cross-linked by an anionic crosslinker sodium tripolyphosphate [TPP]. Optimization of nanoformulations was done by 32 full factorial design using chitosan and TPP concentration[s] as the independent variables and particle size,% entrapment efficiency and% cumulative drug release as the responses. The experimental design was validated by extra design check point formulation [N10]. The optimized formulation [N4] selected on the basis of highest desirability factor [0.895] was developed as in situ gelling system using carbapol934 and evaluated. The best in situ gelling formulation [N4G5] was sufficiently mucoadhesive, corneal toxicity, antibacterial activity and free from ocular irritancy

Preparation, characterization and pharmacodynamic evaluation of fused dispersions of simvastatin using PEO-PPO block copolymer

The solubility enhancement of poorly soluble compounds is an important task in pharmaceutical technology as it leads to better bioavailability and a more efficient application. Fused dispersions [FDs] of simvastatin [SIM] using PEO-PPO block copolymer were prepared which paved the way for the formation of an amorphous product with enhanced dissolution and bioavailability. The accumulative solubility of simvastatin [SIM] from PEO-PPO block copolymer [Lutrol NF 127 prill surfactant] was found to be superior to the drug alone which may be due to the increased oxyethylene content that played the major role in solubility enhancement. A 3[2] full factorial approach was used for optimization wherein the temperature to which the melt-drug mixture cooled [X[1]] and the drug-to-polymer ratio [X[2]] were selected as the independent variables and the time required for 90% drug dissolution [t[90%]] was selected as the dependent variable. A low level of X[1] and a high level of X[2] were suitable for obtaining higher dissolution of SIM from SIM FDs. On increasing melt to cool drug temperature, t[90%] increased thus improving dissolution rate of FD[2] batch with the maximum drug release [99.63%] in 120 min. The optimized FDs were characterized by saturation solubility study, drug content, in-vitro dissolution, fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, x-ray diffraction, [1]HNMR spectroscopy and pharmacodynamic evaluation. Capsules containing optimized FDs were prepared and compared with marketed brand [SIMVOTIN[registered]]. Finally, it can be concluded that the optimized FDs of SIM ameliorate the solubility and dissolution of drug with improved pharmacodynamic activity