Colon delivery of 5 – Fluoro uracil using cross-linked chitosan microspheres coated with eudragit S 100

5-Fluorouracil though recommended as a chemotherapeutic agent for colorectal cancer, suffers from severe systemic toxicity and so needs site-specific delivery. Objective of present investigation is to design slow release enteric coated solid formulations to avoid drug release in stomach and upper small intestine but slowly to build up required drug concentration in the colon. Chitosan microspheres were prepared by emulsification method using gluteraldehyde as cross linking agent. The microspheres were then coated with Eudragit S – 100 by emulsion solvent evaporation method. The coated microspheres were characterized for particle size, entrapment efficiency and surface characteristics. In-vitro drug release profile was studied by changing pH media as per USP protocol and the data was subjected to kinetic interpretations. The optimized microspheres showed particle size in the range of 62 to 65 μm with 65 ± 2% drug entrapment. Eudragit coated chitosan microspheres showed particle size increase upto 390 ± 2 μm with nearly spherical shape and smooth surface. In vitro drug release profile of uncoated microspheres was typical like conventional dosage forms with 38 %, 62 % and 88 % drug release at the end of 2 hrs, 6 hrs and 10 hrs respectively. Coated microspheres showed no drug release in SGF (2hrs), negligible release (8 %) in 6hrs but substantial release of 95% in 24 hours in simulated colon media. Drug distribution in GI following oral administration of coated microspheres in wistar rats showed 84% of the drug accumulation in colon.Keywords: 5-FU; colon-targeting; chitosan; microspheres; Eudragit S-100

Development and validation of reversed-phase HPLC gradient method for the estimation of efavirenz in plasma.

Efavirenz is an anti-viral agent of non-nucleoside reverse transcriptase inhibitor category used as a part of highly active retroviral therapy for the treatment of infections of human immune deficiency virus type-1. A simple, sensitive and rapid reversed-phase high performance liquid chromatographic gradient method was developed and validated for the determination of efavirenz in plasma. The method was developed with high performance liquid chromatography using Waters X-Terra Shield, RP18 50 x 4.6 mm, 3.5 μm column and a mobile phase consisting of phosphate buffer pH 3.5 and Acetonitrile. The elute was monitored with the UV-Visible detector at 260 nm with a flow rate of 1.5 mL/min. Tenofovir disoproxil fumarate was used as internal standard. The method was validated for linearity, precision, accuracy, specificity, robustness and data obtained were statistically analyzed. Calibration curve was found to be linear over the concentration range of 1-300 μg/mL. The retention times of efavirenz and tenofovir disoproxil fumarate (internal standard) were 5.941 min and 4.356 min respectively. The regression coefficient value was found to be 0.999. The limit of detection and the limit of quantification obtained were 0.03 and 0.1 μg/mL respectively. The developed HPLC method can be useful for quantitative pharmacokinetic parameters determination of efavirenz in plasma

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients

Gradient program for the mobile phase during analytical method development.

<p>Gradient program for the mobile phase during analytical method development.</p

Chromatogram for specificity study.

<p>Chromatogram for specificity study.</p

Structure of efavirenz.

<p>Structure of efavirenz.</p

Representative chromatographic peaks obtained during analytical method development.

<p>Representative chromatographic peaks obtained during analytical method development.</p

Chromatogram for precision study.

<p>Chromatogram for precision study.</p