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Objectives Polymeric nanoparticles are a promising novel drug delivery system and have advantages in cancer therapy. Etoposide is an anticancer agent that is used in the treatment of a variety of malignancies. The aim of the present study was to prepare and evaluate novel polymeric nanoparticles containing etoposide. Materials and methods A 32 full factorial design was used to study the effect of Eudragit EPO and Pluronic F-68 on the characterization of nanoparticle suspensions. The polymeric nanoparticles were prepared by nanoprecipitation technique. The prepared nanoparticles was evaluated by percentage yield, drug polymer compatibility using fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetric (DSC) analysis, drug content, entrapment efficiency, zeta potential, particle size, scanning electron microscopy, X-ray diffraction, in vitro drug release studies, kinetic modeling, stability studies, and in vivo animal studies. Response surface plots were studied, which were generated using PCP dissolution software. Results Scanning electron microscopic studies confirmed their porous structure with a number of nanochannels. The FTIR spectra showed the stable character of etoposide in a mixture of polymers and revealed the absence of drug-polymer interactions. The DSC study revealed that the drug was involved in complexation with nanoparticles. The average particle size of etoposide nanoparticles was in the range of 114.4 nm to 136.7 nm. The zeta potential values were attained to ensure good stability of nanosuspensions. In vitro release of the drug from nanoparticles follows the Peppas model and showed controlled release behavior for a period of 24 h. The optimized nanoparticles were subjected to stability studies at 4°C in a refrigerator and the most suitable temperature for storage of etoposide nanoparticles found. The average targeting efficiency of drug-loaded nanoparticles was 41.88±0.030% of the injected dose in the liver, 25.66±0.320% in the spleen 13.82±0.090% in the lungs, 4.52±0.300% in the kidney, and 4.18±0.490% in the brain. Conclusion Etoposide loaded nanoparticles was found to be effective in sustained release.

Graphical Abstract An advanced third generation solid dispersion of TDL comprising polymer in combination with a Self Microemulsifying Composition of TDL (TDL-SMEC-SD) was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD exhibited rapid in-vitro release and bioenahcement with high relative bioavailability and improved therapy in pyelonephritis. Unlabelled image, Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDL-SMEC-SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml) in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w), exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation (globule size ~100 nm) in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMEC-SD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.

International audience; The purpose of this study was to develop a taste-masked quinine sulphate dosage form as a flexible pediatric formulation tool. Pellets were produced as they offer more flexibility to body weight dose adaptation and therefore represent an alternative to tablet breaking in pediatrics. Quinine sulphate pellets were produced via extrusion-spheronisation. Next pellets were coated using Eudragit E PO to obtain a taste-masked formulation. Using 15% dibutyl sebacate (based on polymer weight) as a plasticizer in the formulation caused rapid pellet agglomeration during storage at 40 degrees C and 75% relative humidity. Using stearic acid (15% based on polymer weight) as plasticizer yielded pellets which were less sensitive to sticking. Quinine sulphate release in water within the first 5 min of dissolution testing: 9.2%, 5.9% and 2.1% of the drug dose was released from pellets coated with 10%, 20% and 30% (w/w) Eudragit E PO, respectively. These observations correlated well with the bitterness score of the formulations determined via the Astree electronic tongue and its Bitterness Prediction Module, showing that 20% (w/w) Eudragit E PO was required to obtain a homogeneous film and to delay quinine sulphate release sufficiently to mask the bitterness after drug administration. In acid medium immediate quinine sulphate release was obtained.

Background The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. Results The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Conclusions Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics.