Toxicity Study of a Self-nanoemulsifying Drug Delivery System Containing N-methyl pyrrolidone.

Recently within the lipid based formulation category, Self-nanoemulsifying drug delivery system (SNEDDS) has received considerable attention in the enhancement of bioavailability of poorly water-soluble drugs. Self-emulsifying formulation should have good solvent properties to allow appropriate solubility of the drug in the formulation. Drug incorporated in the formulation should also be readily dissolved as clear and monophasic liquid at ambient temperature when introduced to aqueous phase. N-methyl pyrrolidone (NMP) is one of the main pharmaceutical cosolvents and is a solubilizing excipient used in parenteral and oral medications. Marketed Leuprolide acetate (Sanofi-aventis, Quebec, Canada) is formulated as a solution composed of 55-66% NMP and 34-45% poly(DL-lactide-co-glycolide). Self-emulsifying oral formulation of fenofibrate containing NMP as solubilizer has been patented. Based on these reports we successfully developed SNEDDS formulation using NMP as cosolvent and found ~ 4 fold improvement in apparent permeability coefficient of model drug. To ensure the safety of the developed SNEDDS formulation, in the present study we further investigated its toxicity studies in mice and evaluated for various parameter. From the results it can be concluded that oral administration of SNEDDS formulation containing NMP did not exhibit significant toxicity in mice and further detail toxicity study is required so as to ensure the safety of this system in oral drug delivery.

Enhancement of transdermal penetration and bioavailability of poorly soluble acyclovir using solid lipid nanoparticles incorporated in gel cream.

The objective of this work was to increase the amount of acyclovir in the basal epidermis, site of herpes virus simplex infection, using the solid lipid nanoparticles loaded gel cream as carriers. Solid lipid nanoparticles were prepared by high pressure homogenisation method and incorporated in a semisolid submicron gel cream. Acyclovir distribution into rat skin after topical application of solid lipid nanoparticles loaded gel cream was determined by fabricated Franz diffusion cell. The results showed that, the quantity of the acyclovir in the basal epidermis with the solid lipid nanoparticles loaded submicron gel cream was two folds times more than marketed acyclovir gel cream. This type of carrier can improve acyclovir loaded therapy since it increases drug retention in the basal epidermis.

Topical delivery of aceclofenac from lecithin organogels: preformulation study.

The purpose of this research is to evaluate the suitability of lecithin organogels containing aceclofenac for topical application. The present article focuses on the preformulation part of the whole research work. Thin layer chromatography was carried out to determine lecithin's purity. The excipients for formulating lecithin organogel were screened. Lecithin organogels are thermo reversible in nature and hence gelation temperature study was carried out to determine the temperature where Sol-Gel and Gel-Sol transformation takes place. Partition coefficient of the drug was estimated. Drug solubility in plain oil and organogel containing reverse micelles was estimated. Effect of water added on the properties of lecithin organogels such as X-ray diffraction pattern, conductivity and viscosity were determined. Microscopy of the gel sample has been carried out at different magnifications. The pseudo ternary phase diagram has been constructed to determine the organogel existence region. The permeation study of aceclofenac from different concentrations of lecithin organogels [200 mM, 300 mM and 400 mM] has been determined using cellulose acetate membrane (0.45 micro) and excised rat skin. Lecithin organogel in ethyl oleate has desired stability and consistency. A single spot on the TLC plate confirms the purity of soy lecithin to be used in organogel formation. Aceclofenac solubility was found to be more in lecithin/oil reverse micellar system as compared to its solubility in oil. The X-ray diffraction pattern confirms the incorporation of water in micellar gel network. The physical properties of organogels are affected by water incorporated and concentration of gelator. The permeation of aceclofenac through artificial membrane and excised rat skin demonstrated the same trend and were in the following order 200 mM>300 mM>400 mM. The results showed that organogel exhibits useful pharmaceutical properties.