Arti Gupta

Chitosan–pectin polyelectrolyte complex as a carrier for colon targeted drug delivery

OBJECTIVE The objective of present work was to prepare a polyelectrolyte complex (PEC) between chitosan (polycation) & pectin (polyanion) and to develop enteric coated tablets for colon delivery using the PEC. METHODOLOGY The PECs were prepared using different concentrations of chitosan and pectin. Drug loaded enteric coated tablets were prepared by wet granulation method using PEC to sustain the release at colon and coating was done with Eudragit S 100 to prevent the early release of the drug in stomach and intestine. Two independent variable, % PEC (chitosan/pectin) and % coating were optimized by 3(2) full factorial design. Statistical model were also used to supplement the optimization. DSC was performed to confirm the interaction between the polyions. Developed formulations were evaluated for physical appearance, weight variation, thickness, hardness, friability, % swelling, assay, in-vitro and ex-vivo drug release studies to investigate the PECs ability to deliver the drug to colon. Ex-vivo release study using rat caecal content was also carried out on optimized formulation. RESULTS AND DISCUSSION DSC results confirmed chitosan/pectin interaction and subsequent formation of PEC. The optimized formulation containing 1.1% of PEC and 3% of coating showed highest swelling and release in alkaline pH mechanism of which was found to be microbial enzyme dependent degradation established by ex-vivo study using rat caecal content.

Determination of Quercetin a Biomarker in Hepatoprotective PolyherbalFormulation through High Performance Thin Layer Chromatography

Background: Quercetin was determined in bioactive fractions of Ocimum gratissimum, Butea monosperma, Bauhinia variegate and polyherbal hepatoprotective formulation by HPTLC method. Methods: Polyherbal hepatoprotective formulation was developed by using five bioactive fractionated extracts of three plants namely Butea monosperma, Bauhinia variegate and O. gratissimum. All three plants contain quercetin. Chromatographic separation was performed on aluminium foil plates coated with 200 μm silica gel 60F254 Linear ascending development with toluene:ethyl acetate:formic acid, 5:4:0.1 (v/v/v) was performed at room temperature (25 ± 2°C) in a twin-trough glass chamber saturated with mobile phase vapor. Compact bands (Rf=0.38) were obtained for quercetin. Spectro densitometric scanning was performed in fluorescence mode at 380 nm. The method was validated for precision, recovery, specificity, detection and quantification limits. Results: Linear regression analysis of the calibration plots showed a good linear relationship (R²=0.9843 ± 0.0001) between peak area and concentration in the range 0.5-2.5 μg/band, respectively. The limits of detection and quantification were 0.089 and 0.26 μ/band. The recovery of the method was 97.33-99.11%. Conclusion: The above method was a rapid and cost effective quality-control tool for routine analysis of quercetin in herbal extracts and in pharmaceutical dosage form.

Multiple response optimisation of processing and formulation parameters of pH sensitive sustained release pellets of capecitabine for targeting colon

Abstract Purpose: To optimise the Eudragit/Surelease®-coated pH-sensitive pellets for controlled and target drug delivery to the colon tissue and to avoid frequent high dosing and associated side effects which restrict its use in the colorectal-cancer therapy. Methods: The pellets were prepared using extrusion-spheronisation technique. Box–Behnken and 32 full factorial designs were applied to optimise the process parameters [extruder sieve size, spheroniser-speed, and spheroniser-time] and the coating levels [%w/v of Eudragit S100/Eudragit-L100 and Surelease®], respectively, to achieve the smooth optimised size pellets with sustained drug delivery without prior drug release in upper gastrointestinal tract (GIT). Results: The design proposed the optimised batch by selecting independent variables at; extruder sieve size (X1 = 1 mm), spheroniser speed (X2 = 900 revolutions per minute, rpm), and spheroniser time (X3 = 15 min) to achieve pellet size of 0.96 mm, aspect ratio of 0.98, and roundness 97.42%. The 16%w/v coating strength of Surelease® and 13%w/v coating strength of Eudragit showed pH-dependent sustained release up to 22.35 h (t99%). The organ distribution study showed the absence of the drug in the upper part of GIT tissue and the presence of high level of capecitabine in the caecum and colon tissue. Thus, the presence of Eudragit coat prevent the release of drug in stomach and the inner Surelease® coat showed sustained drug release in the colon tissue. Conclusion: The study demonstrates the potential of optimised Eudragit/Surelease®-coated capecitabine-pellets for effective colon-targeted delivery system to avoid frequent high dosing and associated systemic side effects of drug.

Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology

BACKGROUND In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. OBJECTIVES Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. METHODS Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. RESULTS The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. CONCLUSION The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide.

Cell Line and Augument Cellular Uptake Study of statistically optimized sustained release capecitabine loaded Eudragit S100/PLGA(poly(lactic-co-glycolic acid)) Nanoparticles for colon targeting

BACKGROUND Capecitabine, an anti cancer drug, has a very short drug elimination half-life (0.49 to 0.89 h). High doses and absence of targeting ability in the colon region may lead to more side effects to the patients with colon cancer. PURPOSE To develop and optimize sustained release nanoparticles for effective treatment of colon cancer. METHODS Eudragit S100-PLGA(poly (lactic-co-glycolic acid)) nanoparticles were prepared by a double emulsification, solvent evaporation method followed by high-pressure homogenisation evaluated and the particles were evaluated for surface morphology, particle size analysis, polydispersity index, drug content, % entrapment efficiency and in vitro drug release. To optimize the batch a 32 full factorial design was applied. The optimized batch was evaluated for cytotoxicity and cellular uptake study. RESULTS AND DISCUSSION The optimized formulation exhibited 179.25 nm mean particle size, 71.27% of drug entrapment efficiency and 81.824% drug release up to 72 h. When the concentration of capecitabine was increased from 50-500 μg/ml, the % cytotoxicity of nanoparticles and capecitabine (pure drug) increased from 8.5 to 97.70% and 2.7 to 82.23%, respectively. As per a cellular uptake study, the optimized nanoparticles were completely uptaken by HT 29 adenocarcinoma cells within 2 to 4 h. CONCLUSION Optimized Eudragit S100-PLGA nanoparticles are a promising delivery system for colon targeting.