Rat Caecal Contents Research Articles

Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol.

Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of -19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH.

Polysaccharide, fecal microbiota, and curcumin-based novel oral colon-targeted solid self-nanoemulsifying delivery system: formulation, characterization, and in-vitro anticancer evaluation

The use of polysaccharides in preparation of microbially triggered colon-targeted delivery system has been explored extensively to deliver drugs at the colonic site. This type of targeting is attributed to inherent property of polysaccharides by virtue of which they are digested in the gut only by the colonic microflora. In last two decades, the use of fecal microbiota transplantation (FMT) has been reported widely to treat colonic diseases such as Crohn's disease, irritable bowel syndrome, and recurrent Clostridium difficile infection. It has been established that FMT downregulates inflammatory proliferation and pro carcinogenic pathways. Although a few reports exist on the use of colon-targeted FMT capsules in increasing the microbial diversity of gut microflora, they have not been able to establish clinical superiority of the colon-targeted capsules over conventional orally administered capsules. Hence, in the present study, an attempt has been made to utilize a multipronged strategy through a single formulation, wherein an anticancer phytoconstituent, polysaccharides, fecal microbiota extract (FME), and nanodelivery systems have been designed for the effective treatment of colon cancer. Overall, the study is aimed toward the development of an oral colon-targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) in which curcumin (CCM) was loaded. These SNEDDS were added to polysaccharide mixture of guar gum, pectin, lactose along with aerosol 200 (A-200) and then to the slurry of fecal microbiota extract. The liquid was then freeze dried and developed into solid SNEDDS powder. The process of formulating liquid SNEDDS was optimized using ternary phase diagram and Box Behnken Design. The developed formulation was characterized for physicochemical, physicomechanical, drug release and cytotoxic potential studies. The droplet size of reconstituted S-SNEDDS was found to be 78.46 ± 0.87 nm. The site-specific release of S-SNEDDS powder was confirmed by dissolution studies in medium containing rat caecal contents, wherein, the formulation containing guar gum and pectin in 1% w/w ratio showed less than 10% drug release in initial 5 h and burst release between 5th and 10th h indicating colon-specific release of CCM. Significant cytotoxic effect was seen for CCM-loaded S-SNEDDS as compared to control formulations. The use of 16s metagenomic technique confirmed no significant change in fecal microbiota composition of formulation pre- and postlyophilization. Overall, the study suggested a novel, oral colon-targeted SNEDDS-based formulation containing fecal microbiota and CCM for the treatment of colon cancer.

Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: A smart pH-responsive and receptor-targeted system for colorectal cancer therapy

Glycosylated pH-sensitive mesoporous silica nanoparticles (MSNs) of capecitabine (CAP) were developed for targeting colorectal cancer. The MSNs possessed an average pore diameter of 8.12 ± 0.43 nm, pore volume of 0.73 ± 0.21 cm3/g, and particle size of 245.24 ± 5.75 nm. A high loading of 180.51 ± 5.23 mg/g attributed to the larger pore volume was observed. The surface of the drug-loaded MSNs were capped with chitosan-glucuronic acid (CHS-GCA) conjugate to combine two strategies viz. pH-sensitive, and lectin receptor mediated uptake. In vitro studies demonstrated a pH-sensitive and controlled release of CAP which was further enhanced in the presence of rat caecal content. Higher uptake of the (CAP-MSN)CHS-GCA was observed in HCT 116 cell lines. The glycosylated nanoparticles revealed reduction in the tumors, aberrant crypt foci, dysplasia and inflammation, and alleviation in the toxic features. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as a effective carrier against cancer.

Development of nitazoxanide-loaded colon-targeted formulation for intestinal parasitic infections: centre composite design-based optimization and characterization

BackgroundThe current investigation is focused on the development and characterization of Eudragit S100 coated nitazoxanide-loaded microbeads as colon-targeted system utilizing central composite design (CCD) and desirability function. The study initiated with the selection of a BCS class II drug nitazoxanide and its preformulation screening with excipients, selection of polymer and identification of concentration for CCD, selection of optimized formulation based on desirability function, and in vitro release studies in simulated gastric and colonic media and stability studies. A two-factor, three-level CCD was employed with two independent variables, i.e. X1 (chitosan % w/v) and X2 (sodium tripolyphosphate % w/v), and three dependent variables, i.e. Y1 (particle size in micrometres), Y2 (percentage yield) and Y3 (percent entrapment efficiency), were chosen. Additionally, surface morphology, mucoadhesion and in vitro drug release studies were also conducted.ResultChitosan concentration showing maximum entrapment and optimum particle size was selected to formulate chitosan beads. The polynomial equation and model graphs obtained from the Design-Expert were utilized to examine the effect of independent variables on responses. The effect of formulation composition was found to be significant (p ˂ 0.05). Based on the desirability function, the optimized formulation was found to have 910.14 μm ± 1.03 particle size, 91.84% ± 0.64 percentage yield and 84.75% ± 0.38 entrapment efficiency with a desirability of 0.961. Furthermore, the formulations were characterized for in vitro drug release in simulated colonic media (2% rat caecal content) and have shown a sustained release of ∼ 92% up to 24 h as compared to in vitro release in simulated gastric fluid.ConclusionThe possibility of formulation in enhancing percentage yield and entrapment efficiency of nitazoxanide and the utilization of CCD helps to effectively integrate nitazoxanide microbeads into a potential pharmaceutical dosage form for sustained release.

Effect of co-administration of probiotics with guar gum, pectin and eudragit S100 based colon targeted mini tablets containing 5-Fluorouracil for site specific release

Oral colon targeted mini-tablets containing 5-Fluorouracil (5-FU) were developed by using guar gum, pectin and Eudragit S100. Probiotics were co-administered to constantly replenish the gut microflora of colon that gets damaged due to pathophysiology of cancer and side effect of 5-FU. Replacement of microbial count ensures that the polysachharide used for sustaining the drug release gets digested to release the drug, once the formulation reaches the colon. The site-specific release of coated tablets was confirmed by dissolution studies in medium containing rat caecal contents (RCC), wherein, the formulation containing Eudragit S100, pectin and guar gum in the ratio of 04:03:03 w/w, showed less than 10% drug release in initial 5 h and immediate burst release (100%) between 5th to 10th hour. The cell line studies carried for pooled dissolution samples indicated that more than 90% cells were viable in all the cases till 5th hour. Significant (p < 0.05) decline in cellular viability was observed in case of coated mini tablets as compared to un-coated one. The pharmacokinetic studies showed a lower as well as delayed plasma concentration in the coated formulations endorsing the original hypothesis of reduction in drug exposure of the non-target sites.

SYNTHESIS AND CHARACTERIZATION OF THIOLATED JACKFRUIT SEED STARCH AS A COLONIC DRUG DELIVERY CARRIER

Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon.&#x0D; Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics.&#x0D; Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics.&#x0D; Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon.

Development of novel pH–responsive dual crosslinked hydrogel beads based on Portulaca oleracea polysaccharide-alginate-borax for colon specific delivery of 5-fluorouracil

This study aimed to explore the colon targeting potential of novel polymeric beads encapsulating the anticancer drug 5-fluorouracil (5-FU) prepared utilizing Portulaca plant mucilage. Polysaccharide gel matrix was prepared by using ionotropically gelled mixture of biopolymers sodium alginate and Portulaca polysaccharide, which was isolated from leaves of Portulaca oleracea and was then cross-linked with borax for effective control of drug release in colon. Size and morphology of the prepared beads were characterized using scanning electron microscope (SEM). Other parameters evaluated were drug encapsulation efficiency and cumulative in vitro drug release using rat caecal content and different pH media to simulate the gastrointestinal tract. This novel pH responsive biopolymer provides an option to use plant-based mucilage for colon-specific drug delivery. These natural polysaccharides can form hydrogels and they have an added advantage of being categorized under GRAS (generally recognised as safe) with additional benefits of biocompatibility, biodegradability and specificity towards drug targeting to colon.

A NOVEL APPROACH OF LOCUST BEAN GUM MICROSPHERES FOR COLONIC DELIVERY OF MESALAMINE

Objective: The objective of the present study was to formulate site-specific drug delivery of mesalamine using Locust bean gum.Methods: The core microspheres were prepared by ionic gelation method using CaCl2 solution and cross-linked with glutaraldehyde and were further coated with pH-sensitive polymer eudragit S-100(1.5-4.5 ml) to retard the drug release in the upper gastrointestinal environment (Stomach and small intestine). Microspheres were characterized by ftir spectroscopy, differential scanning calorimetry and evaluated by scanning electron microscopy (SEM), particle size analysis, entrapment efficiency and in vitro drug release studies in different simulated gastric fluids. Stability studies were carried out for one month at 40±2 °C/75±5% RH.Results: The SEM images revealed the surface morphology was rough and smooth for core and coated microspheres, respectively. The optimized batch (ILBG6) of core microspheres(for 7hr), coated microspheres and coated microspheres in presence of rat caecal contents (8%w/v) for 24hr exhibited 98.44±2.48, 73.58±3.49 % and 98.28±4.42 drug release, respectively. The drug release from all locust bean gum microsphere formulations followed higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the korsmeyer-peppas equation with an fickian kinetics mechanism. Finally, stability studies suggested the change in entrapment efficiency and in vitro drug release of microspheres was minimal, indicating good stability of the formulation.Conclusion: The microspheres formed using natural polysaccharide locust beangum by ionic gelation method are capable of colon targeting the anti-inflammatory drug, mesalamine for the treatment of ulcerative colitis.

Fabrication and Evaluations of Dual Crosslinked Mesalamine containing Pectin-Chitosan gel micro beads for controlled and targeted colon delivery

Objectives: The aim of the present work was to prepare and characterize mesalamine loaded microbeads (MLM) consisting of optimized ratios of chitosan and pectin polysaccharides using ionic gelation technique for management of inflammatory bowel disease. Methodology: Mesalamine loaded microbeads were prepared using ionotropic gelation method that was double cross linked with calcium chloride (3-6%, w/v) and sodium sulphate (2-4%, w/v) solutions. The formulation was optimized with the help of two levels and three factors factorial design method. The optimization parameters selected for formulation variables were viz., pectin-chitosan ratio, calcium chloride-sodium sulphate ratio and curing time. The prepared formulations were further characterized on the basis of particle size, shape, swelling index, entrapment efficiency, and percentage yield and in vitro drug release studies. The in vitro release studies using rat caecal content (2 and 4 % w/v) was also performed to simulate the human colonic condition. Results: The mean particle size, entrapment efficiency and percentage yield of MLM were ranged from 875.45 to 975.45 µm, 72.2 to 86.7% and 93.6 to 97.9% respectively. The swelling index of MLM formulations revealed lesser into acidic medium, while augmented swellings were found to be at pH 6.8 and 7.2 respectively. The swelling degree was found to be 7.34 to 13.88% into SIF at pH 6.8 whereas, intensely swelled was 16.24 to 46.02% into SCF at pH 7.2 during 8 h studies. In vitro drug release profile of MLM exhibited that only 1.28 to 4.42 drug was released at simulated gastric fluid (SGF, pH 1.2, 2 h), however optimum drug released was found into simulated intestinal fluid (SIF, pH 6.8, 3 h) i.e. 5.33 to 31.33% and into simulated colonic fluid (SCF, pH 7.2, 18 h) i.e. 32.13 to 87.12% correspondingly. Scanning electron microscopy (SEM) revealed that the microbeads were consisting of semispherical and wrinkled rough surfaces. Further, the rat caecal contents (2 and 4% w/v) release studies confirmed for complete polymeric degradation by colonic enzymes. The release kinetics and mathematical modeling studies carried out for optimized formulation shown that the optimized formulations were of non fickian mechanism (n=0.49 to 0.74) type governed by both diffusion and erosion controlled following Higuchi and Korsemeyer peppas model fittings. Conclusion: It can be concluded from the study that the optimized MLM formulations may be effective for colon targeting and treating inflammatory bowel disease.

Functionally modified polyacrylamide-graft-gum karaya pH-sensitive spray dried microspheres for colon targeting of an anti-cancer drug

An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity. The in-vitro drug release suggested that the microspheres prepared using native GK were incapable to retard the drug release within 5h in the environment of stomach and small intestine. While, those microspheres prepared using pH-sensitive PAAm-g-GK copolymer having crosslinked with glutaraldehyde (GA), released little amount of drug within 5h, but maximum amount of drug was targeted to colonic region in a controlled manner up to 24h. For example, GK10 Microspheres showed only 19.16% drug release at the end of 5th h, while about 80.14% of drug was targeted to colonic region. Cross-linking with GA reduced the early drug release in the upper part of gastrointestinal tract and guaranteed maximum drug release in the colonic region. A rapid enhancement in drug release was witnessed in rat caecal content medium due to the action of colonic bacteria on PAAm-g-GK copolymer.

Novel spray dried pH-sensitive polyacrylamide-grafted-carboxymethylcellulose sodium copolymer microspheres for colon targeted delivery of an anti-cancer drug

Unique pH-sensitive spray dried microspheres were formulated employing hydrolyzed polyacrylamide-g-carboxymethylcellulose sodium (PAAm-g-NaCMC) co-polymer for colon targeted delivery of an anticancer drug, capecitabine. Synthesis of PAAm-g-NaCMC was carried out through free radical polymerization, which was supported with an inert atmosphere and then the alkaline hydrolysis was performed and subjected for characterization including FTIR spectroscopic analysis, 1H NMR spectroscopic analysis, elemental analysis, viscosity measurement, neutralization equivalent and thermo-gravimetric investigation. The swelling data suggested that the PAAm-g-NaCMC possesses significant pH-sensitive property. The microspheres were in the range of 1.00 to 7.34 μ and the drug entrapment efficiency ranged between 70.98 and 94.41%. In vitro drug release suggested the failure of microspheres formulated using native NaCMC which failed to impede drug release in stomach and small intestine, while those prepared with pH-sensitive PAAm-g-NaCMC copolymer and cross-linked with glutaraldehyde are suitable for colon targeting because they retarded release of drug in physiologic atmosphere of stomach and small intestine. Only 12.97% of drug was released from CMC10 formulation by the end of 5th h and rest of drug has been targeted to colonic region. A sudden increase in release of drug was observed in rat caecal contents media because of colonic bacterial action on PAAm-g-NaCMC copolymer.

Amidated pectin/sodium carboxymethylcellulose microspheres as a new carrier for colonic drug targeting: Development and optimization by factorial design

The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn2+ and Al3+ ions and test their potential for colonic targeting of progesterone. A 24 factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82–99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al3+ ion concentration. Drug release was minimal during the first 3h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle.

In vitro and in vivo evaluation of the prebiotic effect of raw and roasted almonds (Prunus amygdalus).

BACKGROUNDAlmonds contain considerable amounts of potential prebiotic components, and the roasting process may alter these components. The aim of this study was to compare the in vitro fermentation properties and in vivo prebiotic effect of raw and roasted almonds.RESULTS In vitro, predigested raw and roasted almonds promoted the growth of Lactobacillus acidophilus (La‐14) and Bifidobacterium breve (JCM 1192), and no significant differences were found between these two nuts. In a 4‐week animal trial, daily intake of raw or roasted almonds promoted the population of Bifidobacterium spp. and Lactobacillus spp. and inhibited the growth of Enterococcus spp. in faeces and caecal contains of rats. Compared with roasted almonds, raw almonds had a greater bifidobacteria promotion effect. Besides, significantly higher β‐galactosidase activity and lower β‐glucuronidase and azoreductase activities in faeces or caecal contents of rats were observed with raw almonds than with roasted almonds. While, in terms of metabolic effects, the ingestion of roasted almonds resulted in significantly greater intestinal lipase activities.CONCLUSIONBoth raw and roasted almonds exhibit potential prebiotic effects, including regulation of intestinal bacteria and improved metabolic activities. The roasting process may slightly reduce the prebiotic effects of almonds but significantly improve the metabolic effects.© 2016 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin

Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting.

Swelling, erosion and drug release characteristics of Sodium Diclofenac from heterogeneous matrix tablets

The aim of this study was to investigate the effect of combination lipophilic (Acryl-EZE®) and hydrophilic (HPMC) polymers on the release of Sodium Diclofenac (DS) from a tablet. The microgranules were prepared using a fluidized bed followed by direct compression. Swelling and erosion studies of polymer matrix tablets were carried out in various media. The matrix tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The swelling action of matrices was controlled by the rate of its hydration in the medium. The in vitro release was examined with and without rat caecal contents. Release studies showed that the swelling and erosion influenced the drug release. The good fit to Higuchi equation, the n values from Korsmeyer equation and the prevalence of kd over kr in Peppas-Sahlin equation revealed a drug release mechanism controlled mainly by diffusion.

Preparation, Evaluation and Optimization of Multiparticulate System of Mebendazole for Colon Targeted Drug Delivery by Using Natural Polysaccharides.

A Multiparticulate system of Mebendazole was developed for colon targeted drug delivery by using natural polysaccharides like Chitosan and Sodium-alginate beads. Chitosan microspheres were formulated by using Emulsion crosslinking method using Glutaraldehyde as crosslinking agent. Sodium-alginate beads were formulated by using Calcium chloride as gelling agent. Optimization for Chitosan microspheres was carried out by using 2(3) full factorial design. 3(2) full factorial design was used for the optimization of Sodium-alginate beads. The formulated batches were evaluated for percentage yield, particle size measurement, flow properties, percent entrapment efficiency, Swelling studies. The formulations were subjected to Stability studies and In-vitro release study (with and without rat caecal content). Release kinetics data was subjected to different dissolution models. The formulated batches showed acceptable particle size range as well as excellent flow properties. Entrapment efficiency for optimized batches of Chitosan microspheres and sodium alginate beads was found to be 74.18% and 88.48% respectively. In-vitro release of drug for the optimized batches was found to be increased in presence of rat caecal content. The best-fit models were koresmeyer-peppas for Chitosan microspheres and zero order for sodium-alginate beads. Chitosan and Sodium-alginate was used successfully for the formulation of Colon targeted Multiparticulate system.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

MICROBIAL TRIGGERED COLON TARGETED COMPRESSION COATED TABLETS OF TENOXICAM: FORMULATION AND EVALUATION

The present investigation deals with to formulation and evaluation of colon specific drug delivery system of Tanoxicam by compression coated tablet technique. Tenoxicam, Avicel pH101, HPMC K4M, Guar gum were used as components.Tenoxicam compression coated tablets were prepared and evaluated for differential scanning colorimetry (DSC), FTIR spectroscopy and in-vitro dissolution study without rat caecal content and with rat caecal content. The results suggest that Colon specific drug delivery system of Tenoxicam compression coated tablets were formulated successfully by using natural polymer such as Guar gum in combination with different concentration of HPMC. Tablets were evaluated for drug content, hardness, thickness, friability, weight variation, in-vitro dissolution and all the results were found within the specification. As the concentration of HPMC in compression coat increased, drug release was decreased. Based on in-vitro drug release study, it was concluded that compression coated tablets with combination of 90% Guar gum and 10% HPMC could produce a successful drug targeting to the colon with minimal amount released in the stomach and small intestine for tenoxicam.

Colon specific drug delivery of tramadol HCl for chronotherapeutics of arthritis.

Objective:The objective of present work is to develop and evaluate a matrix system for Chronotherapeutic delivery of centrally acting of opioid analgesic (tramadol HCl) to treat nocturnal symptoms of arthritis using almond gum as carrier.Materials and Methods:Matrix tablets of tramadol HCl were prepared by using 30, 40, 50, 60 and 70% w/w of tablet of gum badam as carrier by wet granulation technique. These tablets were compression coated with eudragit S100 to prevent drug release in stomach. All formulations were evaluated for hardness, friability, weight variation, drug content, in vitro and in vivo studies. The almond gum was characterized by viscosity measurements and Fourier transform infrared analysis. The coated (FC1 to FC5) and uncoated tablets (F1 to F5) were evaluated for in vitro release of tramadol HCl after sequential exposure to pH 1.2, pH 7.4 and pH 6.8 respectively for 2 h, 3 h and 19 h in the absence as well as presence of rat caecal content and the corresponding data was fitted to popular release kinetic equations in order to evaluate the release mechanisms-kinetics. The selected formulation was subjected to in vivo targeting efficacy studies by roentgenography technique.Results and Discussion:In vitro release studies indicated that the matrix tablets (F1 to F5) failed to control the drug release in the physiological environment of stomach and small intestine. On the other hand, compression coated formulations were able to protect the tablet cores from premature drug release. Presence of rat caecal content enhances the drug release from the tablets as the concentration of polymer increased, drug release was found to be retarded. The release of tramadol from all the formulation followed zero order with non fickian diffusion. X-ray studies confirmed that the tablet successfully reached colon without getting disintegrated in upper gastrointestinal tract.Conclusion:Based on the results, selective delivery of tramadol HCl to the colon could be achieved using 60% w/w (FC4) of almond gum matrix tablets compression coated with eudragit S100.

Ternary Blends of Some Hydrophilic and Hydrophobic Polymers in Colon Targeted Delivery of Diethylcarbamazine = خليط ثلاثي لبعض البوليمرات المحبة للماء و غير المحبة للماء بهدف إيتاء دواء داي إيثيل كاربامازين في القولون

Matrix tablets were prepared using blends of xanthan gum (XG), Guar gum (GG) and ethylcellulose (EC). The polymers were combined using six different ratios; 1:1:1, 1:2:1, 1:2:2, 2:2:1, 2:1:2 and 2:1:1 to produce formulations XG1GG1EC1, XG1GG2EC1, XG1GG2EC2, XG2GG2EC1. XG2GG1EC2 and XG2GG1EC1, respectively. Diethylcarbamazine (DEC) was used as the model drug. The ability of the prepared matrices to target drug release at the colon under the influence of colonic bacteria was evaluated using the dissolution medium containing 4% caecal content. Optimum release of drug was observed with formulations XG2GG2EC1 and XG2GG1EC1 with maximum drug release of 75 and 81%, respectively. Significant difference (P<0.05) was observed between drug release in dissolution medium with and without rat caecal contents for the batches of DEC tablets. Formulations (XG2GG2EC1 and XG2GG1EC1) followed Korsemeyer models (r2 = 0.9903 and r2 =0.9955) respectively via non – fickian diffusion (n ≥ 0.45).