Development, optimization, and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers.
The present studies entail formulation development of novel solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of valsartan with improved oral bioavailability, and evaluation of their in vitro and in vivo performance. Preliminary solubility studies were carried out and pseudoternary phase diagrams were constructed using blends of oil (Capmul MCM), surfactant (Labrasol), and cosurfactant (Tween 20). The SNEDDS were systematically optimized by response surface methodology employing 3(3-)Box-Behnken design. The prepared SNEDDS were characterized for viscocity, refractive index, globule size, zeta potential, and TEM. Optimized liquid SNEDDS were formulated into free flowing granules by adsorption on the porous carriers like Aerosil 200, Sylysia (350, 550, and 730) and Neusilin US2, and compressed into tablets. In vitro dissolution studies of S-SNEDDS revealed 3-3.5-fold increased in dissolution rate of the drug due to enhanced solubility. In vivo pharmacodynamic studies in Wistar rats showed significant reduction in mean systolic BP by S-SNEDDS vis-à-vis oral suspension (p < 0.05) owing to the drug absorption through lymphatic pathways. Solid-state characterization of S-SNEDDS using FT-IR and powder XRD studies confirmed lack of any significant interaction of drug with lipidic excipients and porous carriers. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS are found to be stable without any change in physiochemical properties. Thus, the present studies demonstrated the bioavailability enhancement potential of porous carriers based S-SNEDDS for a BCS class II drug, valsartan.
Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Khodasingi, Berhampur, 760 010, Odisha, India.
Sarwar
S
Beg
Suryakanta
S
Swain
Harendra Pratap
HP
Singh
Ch Niranjan
ChN
Patra
M E Bhanoji
ME
Rao
D000042:Absorption; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry*; D005989:Glycerides; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000068756:Valsartan; D014783:Viscosity
D000959:Antihypertensive Agents; D004337:Drug Carriers; D045703:Emulsifying Agents; D005989:Glycerides; D009821:Oils; D009930:Organic Chemicals; D011136:Polysorbates; D013501:Surface-Active Agents; D013607:Tablets; D013777:Tetrazoles; C440220:Labrasol; D000068756:Valsartan; D014633:Valine