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Impact of solid carriers and spray drying on pre/post-compression properties, dissolution rate and bioavailability of solid self-nanoemulsifying drug delivery system loaded with simvastatin

Sharma, Parth, Singh, Sachin Kumar, Pandey, Narendra Kumar, Rajesh, Sarvi Yadav, Bawa, Palak, Kumar, Bimlesh, Gulati, Monica, Singh, Saurabh, Verma, Surajpal, Yadav, Ankit Kumar, Wadhwa, Sheetu, Jain, Subheet Kumar, Gowthamarajan, Kuppusamy, Malik, Adil Hussain, Gupta, Suksham, Khursheed, Rubiya
Powder technology 2018 v.338 pp. 836-846
bioavailability, biopharmaceuticals, carboxymethylcellulose, differential scanning calorimetry, droplet size, drug delivery systems, ethanol, freeze-thaw cycles, hydrophilicity, hydrophobicity, lactose, nanoemulsions, pharmacokinetics, polyvinyl alcohol, powders, rats, scanning electron microscopes, spray drying, stearic acid, thermodynamics
In the present study, different solid self-nanoemulsifying drug delivery system (S-SNEDDS) was formulated by using porous hydrophilic and hydrophobic carriers to improve the dissolution rate and bioavailability of simvastatin (SIM). The prepared liquid-SNEDDS composed of Labrafil M 1944 CS/ Tween-80/ Ethanol (20% / 53.33%/26.67% v/v) with 0.1% SIM, resulted droplet size of 40.69 nm. The hydrophobic carriers used were Aerosil-200, Syloid 244FP, Syloid XDP 3150, Magnesium stearate, Micro Crystalline Cellulose PH102 and lactose and hydrophilic carriers used were Poly vinyl alcohol, Sodium carboxy methyl cellulose and hydroxypropyl-β-cyclodextrin. These S-SNEDDS were characterized through micromeritic, biopharmaceutical studies and stability studies. The spray dried S-SNEDDS prepared by using Aerosil 200 as hydrophobic carrier provided nanoemulsions with unchanged droplet size and drug release when subjected at different stress conditions such as thermodynamic stress and freeze thaw cycles. In vitro dissolution studies revealed that the L-SNEDDS and S-SNEDDS of Aerosil 200 were found to be remarkably superior over the unprocessed SIM and marketed SIM. Scanning electron microscope, Differential scanning calorimeter and Powder X-Ray Diffraction revealed crystalline SIM was present in a changed amorphous state in the SNEDDS formulations prepared with Aerosil 200 as carrier. Further, pharmacokinetic study carried out on rats revealed 0.5 h increase in time for maximal concentration (Tmax), 3.75 folds increase in maximal concentration (Cmax), 1.22 h increase in mean residence time, 1.54 folds increase in area under curve (AUC0-t), 2.10 folds increase in AUC0-∞ and 3.28 folds increase in bioavailability confirms that the developed S-SNEDDS were superior than that of marketed formulation. Hence, it can be safely concluded that Aerosil 200 based S-SNEDDS were able to provide improvement in dissolution rate and oral bioavailability of SIM.