Formulation optimization and characterization of Nanosuspension of Acyclovir

Abstract

Oral administration has been the most favorable route of drug delivery. Nevertheless, many hydrophilic drugs, administered orally exhibit low oral bioavailability mainly due to low permeability. For such BCS class III drugs, gastrointestinal permeation is the rate-controlling step in the absorption process. Many approaches have been tried for improving permeability like Particulate Drug delivery System, Vesicular Drug Delivery System, Polymeric Micelles, Micro Emulsion/Nano Emulsion, SMEDDS/ SNEDDS, Nanosuspension etc. Nanosuspensions are submicron colloidal dispersions of nano sized drug particles stabilized by surfactants. Acyclovir, a class III drug shows only 20% bioavailability. It is having very low permeability (Log P is -1.56) Also, it is having very high onset of action (within 24 hours). Acyclovir is highly hydrophilic compound, so its absorption through intestinal membrane carries out via active transport. The oral cavity is highly vascularized but the surface epithelium is avascular, thus potentially reducing the bioavailability of drug absorbed from the gut to these regions. An interesting property of the oral mucosa is their ability to phagocytose particles, e.g., by Langerhans cells and epithelial cells. Direct nanoparticle uptake is one of the promising methods of improving the bioavailability of active ingredients, especially for compounds that are soluble in water but that have low permeability. Transcytosis of the nanoparticle takes place with the help of M cells, which are located in Peyer’s patches in the small intestine. But, the problem with this approach is that these M cells represent typically less than 1% of the total intestine area, which makes the selective delivery to these sites more difficult. So, surface modification technology was incorporated which includes the use of Eudragit coating. So, with the help of Emulsification Solvent evaporation method, the preparation of nanosuspension of Acyclovir was taking place, along with Eudragit EPO as Polymeric stabilizer and Tween 80 as Surfactant stabilizer. 32 full factorial design was applied for the optimization of the formulation parameters. Various evaluation parameters like Particle size and Zeta potential, % Entrapment efficiency, % Drug release, Ex vivo diffusion study, Differential scanning colorimetry (DSC), Transmission Electron Microscopy (TEM) study etc. were performed and the best batch was optimized.