title: Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent.
abstract: Atorvastatin calcium (ATRC) is a poor water soluble drug used for treatment of hypercholesterolemia. This research is aimed to improve solubility and dissolution rate of ATRC by formulating into solid self-nanoemulsifying drug delivery system (S-SNEDDS) using N-methyl pyrrolidone (NMP) as cosolvent. Solubility of ATRC was determined in various vehicles. Ternary phase diagrams were constructed to identify stable nanoemulsion region. SNEDDS formulations were evaluated for robustness to dilution, thermodynamic stability study, % transmittance, self-emulsification time, globule size and transmission electron microscopy. The optimized liquid SNEDDS showed robust to all dilutions exhibiting no signs of phase separation or precipitation for 24 h. Liquid SNEDDS was transformed into S-SNEDDS using different adsorbents. Differential scanning calorimetry and scanning electron microscopy studies unravel the transformation of native crystalline state to amorphous state/solubilized state. In vitro dissolution study of S-SNEDDS was found to be significantly higher in comparison to that from plain drug, irrespective of pH (p < 0.001). Furthermore, ex vivo permeation studies showed a 4.45-fold improvement in apparent permeability coefficient (Papp) from S-SNEDDS compared to plain drug. In conclusion, S-SNEDDS prepared using NMP as cosolvent provides an effective approach for improved oral delivery of ATRC.
authors: Cachet Pharmaceutical Pvt. Ltd, An ALKEM Group , Baddi, Solan , India and.
authors: Anuj G
authors: AG
authors: Agrawal
authors: Ashok
authors: A
authors: Kumar
authors: Paraag S
authors: PS
authors: Gide
mesh_terms: D000003:Abattoirs; D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006041:Goats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D044367:Phase Transition; D011136:Polysorbates / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry*
chemical_list: D004655:Emulsions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D011760:Pyrrolidinones; C000515:cremophor EL; D000069059:Atorvastatin; C038678:N-methylpyrrolidone; D005990:Glycerol
keywords: Atorvastatin calcium; SNEDDS; bioavailability; emulsion; oral drug delivery; permeability; solubility; surfactant