Formulation and Optimization of Fluvastatin Loaded Self-emulsifying Drug Delivery Systems

Abstract-Introduction: The current research is aimed at formulating and evaluating fluvastatin self-nanoemulsifying drug delivery system (SNEDDS).

Materials and Methods: Fluvastatin SNEDDS formulated using sefsol-218 (oil), Cremophor RH40 (surfactant), and propylene glycol (cosurfactant). The optimal concentration of excipients confirmed by self-emulsification region of pseudo-ternary phase diagram. Fluvastatin SNEDDS optimized by Box– Behnken design employing the study factors – the amount of sefsol-218 (a), Cremophor RH40 (b), and propylene glycol (c) and responses – droplet size (DS) (Y1), zeta potential (Y2), and cumulative percentage of drug release after 60 min (Y3).

Results: The results revealed that FVT8 comprising 30% sefsol-218, 50% Cremophor RH40, and 35% propylene glycol have close agreement between predicted and observed values. The optimized formulation FVT8 exhibited enhanced drug release with minimum DS of 22.1 nm and zeta potential of ‒6.7 mV and maximum drug release 98.62%. The Fourier transform infrared studies indicated no significant interaction among the drug and formulation excipients used; SEM data revealed that particle size is in nanometer range with a Zeta potential indicating higher absorption and stability.

Conclusion: Hence, the results revealed that the use of SNEDDS formulation for fluvastatin increased solubility, dissolution rate and has potential to enhance the bioavailability.

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Introduction
The majority of novel therapeutic moieties in recent years belong to BCS Classes II or IV that exhibit poor aqueous solubility which limit oral administration. Incomplete drug dissolution and precipitation in the gastrointestinal fluids are major factors responsible for the lower bioavailability of the drug. Such drugs are potential candidates for the lipid-based drug delivery system that enhances their oral bioavailability. Advancements in nanotechnology recommend the use of nano-based drug delivery systems to conquer these confines. These systems comprise polymeric nanoparticles, lipid-based systems, and noisome. Self-nanoemulsifying drug delivery system (SNEDDS) is one such approach that enhances the drug release and bioavailability. It is a lipid based system in which drug is carried in a lipid which is exclusively a medium chain triglyceride that spontaneously forms an emulsion on coming in contact with the body fluids, which is stabilized by surfactants that decrease the interfacial tension between the fluids and lipid enabling the drug to get disperse easily and more available for absorption, thus improving drug release and bioavailability. SNEDDS also exhibits long-term stability, higher patient compliance, palatability, reduced drug dosage, ease of formulation, and ease of scale-up which make them superior to other formulation techniques.

Fluvastatin is used to treat hypercholesterolemia and prevents cardiovascular disease, which belongs to Class II drug in BCS classification which suffers with low aqueous solubility. Fluvastatin belongs to statin class that reduces plasma cholesterol levels thus preventing from cardiovasculardisease. It is synthetic HMG-CoA reductase inhibitors that catalyze the conversion of HMG-CoA to mevalonic acid which is rate-limiting step in cholesterol biosynthesis. Continue reading here.

Materials
Fluvastatin, acrysol K140, acrysol EL135, acconon E, acconon CC400, acconon sorb20, Capmul GMO 50, Caprol PGE 860, Caprol ET, Cremophor EL, Cremophor RH40, Gelucire 44/14, Labrasol, Solutol HS15, tween 80, tween 20 and triton-9100, Capmul MCMC8, Lauroglycol 90, PEG 400, PG, EG, Plurol Oleique CC497, triacetin, Transcutol P, propylene Glycol, Capmul MCM, Captex 355, Capmul PG8, Capryol 90, Imwitor 742, IPM, Labrafil M2, Labrafac CC, Labrafac lipophile WL 1349, Maisine 35-1, Miglyol 812, Paceol, sefsol-218, olive oil, oleic acid and castor oil.