Oral Colon Delivery Research Articles

Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance.

Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery.

Anti-oxidant and anti-inflammatory potential of different polymer-based mesalamine delayed-release granules in TNBS-induced ulcerative colitis in wistar rats

Ulcerative colitis (UC) is an inflammatory condition of colon characterized by severe damage to the innermost colon tissues. A number of studies described the use of medication delivery systems based on natural polymers like polysaccharides for the purpose of reaching the colon. In this research, polymer-based mesalamine delayed-release granules (DRGs) were tested for their antioxidant and anti-inflammatory efficacy against UC. Chitosan (C), pectin (P), and pectin-chitosan (PC) mesalamine (M) DRGs were prepared and characterized. Data revealed satisfactory compatibility, flow, packing properties, drug release pattern, and delayed drug release by DRGs. Wistar rats were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg) via rectal administration. Mesalamine and mesalamine DRGs (50 mg/kg) were administered orally separately for 14 days. Biomarkers of oxidative stress, inflammation, hematological tests, colon profile, and histopathology were performed. The findings demonstrated the good efficacy of the polysaccharides in delivering mesalamine to colon. Mesalamine and mesalamine DRGs based on various polymers showed significant antioxidant and anti-inflammatory effects in rats with UC. Mesalamine granules significantly attenuated colon lipid peroxidation, nitrites, myeloperoxidase activity, and interleukin-1β levels, and improved anti-oxidants (GSH, SOD). Data showed upregulation of Nrf2 activity by mesalamine granules with CM-DRGs showing maximum effect. Mesalamine and different polymer-based mesalamine DRGs significantly attenuated TNBS-induced decline in body weight, ulcer severity, and colon damage. CM-DRGs showed the most pronounced ameliorative effect on colon and hematology parameters via anti-oxidant and anti-inflammatory activities. Chitosan can be used as a carrier for oral colon delivery of mesalamine in DRG formulation for enhanced therapeutic efficacy in UC.

Optimization, cellular uptake, and in vivo evaluation of Eudragit S100-coated bile salt-containing liposomes for oral colonic delivery of 5-aminosalicylic acid

Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential. The method of incorporating SG into the lipid or aqueous phase of the liposome did not notably impact the characteristics of the liposomes but the hydration media had a substantial effect on the entrapment efficiency of 5-ASA. In vitro drug release in different fluids simulating distinct gastrointestinal tract sections, indicated pH-dependent disintegration of the coating layer of coated SG-containing liposomes. The majority of the drug was retained when subjected to simulated gastric fluid (SGF) and fed-state simulated intestinal fluid (FeSSIF) (≈ 37% release after 2 h in SGF pH 1.2, followed by 3 h in FeSSIF pH 5). The remaining drug was subsequently released in phosphate-buffered saline pH 7.4 (≈ 85% release within 24 h). Increasing SG concentration in the liposomes decreased the amount of drug released in FeSSIF. Similar results were observed when SG was replaced with sodium taurocholate. Cellular uptake studies in Caco-2 cells demonstrated that all liposomal formulations (conventional liposomes, bile salt-containing liposomes, and coated bile salt-containing liposomes) have shown to be equally effective at increasing the cellular uptake compared to free fluorescein solution. In the pharmacokinetic study, coated bile salt-containing liposomes showed a lower Cmax and prolonged residence in the gastrointestinal tract in comparison to conventional liposomes. Taken together, these findings suggest that the polymer-coated bile salt-containing liposomes have the potential to serve as a drug delivery system targeted at the colon.

Guar gum as a microbially degradable component for an oral colon delivery system based on a combination strategy: formulation and in vitro evaluation.

Oral colon delivery has widely been pursued exploiting naturally occurring polysaccharides degraded by the resident microbiota. However, their hydrophilicity may hinder the targeting performance. The aim of the present study was to manufacture and evaluate a double-coated delivery system leveraging intestinal microbiota, pH, and transit time for reliable colonic release. This system comprised a tablet core, a hydroxypropyl methylcellulose (HPMC) inner layer and an outer coating based on Eudragit® S and guar gum. The tablets were loaded with paracetamol, selected as a tracer drug because of the well-known analytical profile and lack of major effects on bacterial viability. The HPMC and Eudragit® S layers were applied by film-coating. Tested for in vitro release, the double-coated systems showed gastroresistance in 0.1 N HCl followed by lag phases of consistent duration in phosphate buffer pH 7.4, imparted by the HPMC layer and synergistically extended by the Eudragit® S/guar gum one. In simulated colonic fluid with fecal bacteria from an inflammatory bowel disease patient, release was faster than in the presence of β-mannanase and in control culture medium. Thebacteria-containingfluid was obtained by an experimental procedure making multiple tests possible from a single sampling and processing run. Thus, the study conducted proved the feasibility of the delivery system and ability of guar gum to trigger release in the presence of colon bacteria without impairing the barrier properties of the coating. Finally, it allowed an advantageous simulated colonicfluid preparation procedure to be set up, reducing the time, costs, and complexity of testing and enhancing replicability.

Development of a time-dependent oral colon delivery system of anaerobic Odoribacter splanchnicus for bacteriotherapy

Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 106-107 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.

PH-sensitive HPMCP-chitosan nanoparticles containing 5-aminosalicylic acid and berberine for oral colon delivery in a rat model of ulcerative colitis

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

Modification of Octenyl Succinic Anhydride Starch by Grafting Folic Acid and its Potential as an Oral Colonic Delivery Carrier

AbstractIn this study, an oral colonic delivery system is designed using octenyl succinic anhydride (OSA) starch grafted with folic acid (FA). OSA starch with different degrees of substitution (DS) (0.011, 0.027, and 0.039) is prepared by reacting OSA with waxy maize starch. To optimize the drug‐loading efficiency, the study choses OSA6 starch (DS = 0.027) as the substrate to prepare OSA starch grafted with FA (FA‐OSA6). Fourier transform infrared spectrum confirms the successful introduction of FA. The scanning electron micrograph indicates that the surface of the FA‐OSA starch granules is rough and uneven. Drug loading analysis shows that FA‐OSA6 starch efficiently loaded doxorubicin hydrochloride (DOX) up to 87.71%. In vitro release studies suggest that the drug‐loaded complex released only 15.8% DOX through the upper gastrointestinal tract. The cell viability assay shows that the drug‐loaded complex effectively inhibits the growth of colon cancer cells (Caco‐2). These results suggest that OSA6 starch grafted with FA has potential as an oral colonic delivery carrier for DOX.

A review on curcumin colon-targeted oral drug delivery systems for the treatment of inflammatory bowel disease.

Synthetic drugs and monoclonal antibodies are the typical treatments to combat inflammatory bowel disease (IBD). However, side effects are present when these treatments are used, and their continued application could be restricted by the high relapse rate of the disease. One potential alternative to these treatments is the use of plant-derived products. The use curcumin is one such treatment option that has seen an increase in usage in treating IBD. Curcumin is derived from a rhizome of turmeric (Curcuma longa), and the results of studies on the use of curcumin to treat IBD are promising. These studies suggest that curcumin interacts with cellular targets such as NF-κB, JAKs/STATs, MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the progression of IBD. Potentially, curcumin can be used as a therapeutic agent for patients with IBD when it reduces the incidence of clinical relapse. This review discusses the strategies utilized in designing and developing an oral colonic delivery dosage form of curcumin.

In vitro and in vivo evaluation of a pH-, microbiota- and time-based oral delivery platform for colonic release

Several formulation strategies have been proposed for oral colon delivery, particularly for the therapy of inflammatory bowel disease (IBD). However, targeting the large intestine remains a challenging goal. The aim of this study was to develop and evaluate a novel type of drug delivery system, which is based on multiple drug release triggers for reliable performance. The system consists of: (i) a drug core, (ii) an inner swellable low-viscosity hydroxypropyl methylcellulose (HPMC) layer, and (iii) an outer film coating based on a Eudragit® S:high-methoxyl (HM) pectin (7:3 w/w) blend, optionally containing chitosan. Convex immediate release tablets (2 or 4 mm in diameter) containing paracetamol or 5-aminosalicylic acid (5-ASA) were coated in a fluid bed. The double-coated tablets exhibited pulsatile release profiles when changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4. Also, drug release was faster in simulated colonic fluid (SCF) in the presence of fecal bacteria from IBD patients compared to control culture medium from tablets with outer Eudragit® S: HM pectin: chitosan coatings. The latter systems showed promising results in the control of the progression of colitis and alteration of the microbiota in a preliminary rat study.

Time-Based Formulation Strategies for Colon Drug Delivery.

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed.

Potentials of Alginates as Capping Agent for Oral Colon Delivery of Radiosynthesized Silver Nanoparticles: A Review

Radiosynthesized silver nanoparticles (AgNPs) offer benefits for treatment of chronic colon inflammation due to their anti-inflammatory activity. Targeted delivery of AgNPs to the colon allows topical treatment at high concentration but at reduced systemic side effects. Meanwhile, related to drug administration, oral route is a common method. However, the physiology of the gastrointestinal (GI) tract limits the AgNPs ability to achieve their therapeutic level. This is specifically related to the acidic environment of the stomach and mucus layer of the GI tract. Concurently, alginates are one of the most extensively explored biomaterial classes for drug delivery system due to its biocompatibility, gel-forming ability at mild condition, anionic nature, sensitivity, and mucoadhesiveness. In this review we provide an overview of appropriate features of alginates as capping agent for oral delivery of radiosynthesized AgNPs to the colon. As capping agents, alginates play multiple roles specific to its processing stages, i.e., radiosynthesis, stabilization of nanoparticle system, and oral colon delivery devices of AgNPs. Additionally, we describe outstanding features of alginates as capping agents for drug delivery device as well as the positive contributions of radiation processing on improving the functional effects of alginate. Normal 0 false false false EN-ID JA AR-SA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif"; mso-ansi-language:EN-ID;}

Preparation, Characterization and In Vitro Evaluation of Eudragit S100-Coated Bile Salt-Containing Liposomes for Oral Colonic Delivery of Budesonide.

The aim of this study was to prepare a liposomal formulation of a model drug (budesonide) for colonic delivery by incorporating a bile salt (sodium glycocholate, SGC) into liposomes followed by coating with a pH-responsive polymer (Eudragit S100, ES100). The role of the SGC is to protect the liposome from the emulsifying effect of physiological bile salts, while that of ES100 is to protect the liposomes from regions of high acidity and enzymatic activity in the stomach and small intestine. Vesicles containing SGC were prepared by two preparation methods (sonication and extrusion), and then coated by ES100 (ES100-SGC-Lip). ES100-SGC-Lip showed a high entrapment efficiency (>90%) and a narrow size distribution (particle size = 275 nm, polydispersity index < 0.130). The characteristics of liposomes were highly influenced by the concentration of incorporated SGC. The lipid/polymer weight ratio, liposome charge, liposome addition, and mixing rate were critical factors for efficient and uniform coating. In vitro drug release studies in various simulated fluids indicate a pH-dependent dissolution of the coating layer, and the disintegration process of ES100-SGC-Lip was evaluated. In conclusion, the bile salt-containing ES100-coated liposomal formulation has potential for effective oral colonic drug delivery.

Oral colon delivery platform based on a novel combination approach: Design concept and preliminary evaluation

An oral colon delivery platform based on a novel combination strategy, leveraging multiple physiological characteristics of the intestine, is proposed. The system comprises a drug core, a water-swellable/soluble inner layer based on a hydrophilic cellulose derivative and an enteric outer layer (Eudragit® S) containing a microbially-degradable polysaccharide (high-amylose starch, Amylo N460), acting synergistically to prevent early release in the small intestine on the one hand, and release failure on the other. The Eudragit® S:Amylo N460 solid weight ratio in the external coating was 7:3; triethyl citrate and glyceryl monostearate were used as a plasticizer and an anti-tacking agent, respectively. The outer Eudragit® S/Amylo N460 layer was applied in a fluid bed using hydro-alcoholic or aqueous coating formulations. Two types of “inner” systems were studied: (i) Drug-loaded tablets coated with a low-viscosity hydroxypropyl methylcellulose (by aqueous spray-coating), and (ii) hydroxypropyl cellulose capsules prepared by injection-molding (filled with paracetamol as an analytical tracer). The obtained dosage forms were thoroughly characterized, including in vitro release measurements in various media. In all cases, pulsatile release profiles were obtained after medium change from 0.1 N HCl to phosphate buffer pH 7.4, with lag phases depending on the type and preparation technique of the hydrophilic polymer layer. The role of the microbiota on the release performance was explored in simulated colonic fluid (SCF), consisting in culture medium inoculated with fecal samples from inflammatory bowel disease patients. Clear differences in drug release were observed in SCF versus culture medium free of feces, indicating the effect of microbial degradation.

Entrapment of capsaicin loaded nanoliposome in pH responsive hydrogel beads for colonic delivery

Liposomes loaded with capsaicin were encapsulated in alginate hydrogel beads followed by coating with Eudragit S-100 for efficient oral colonic delivery. Liposomes were prepared by thin film hydration method using soyalecithin and cholesterol. Hydrogel beads encapsulating liposome were prepared by iontropic gelation methods which were Eudragit coated. The liposomes and hydrogel beads were characterized for size, entrapment efficiency and in vitro drug release. Coated hydrogel bead has shown better drug release after 5 h and has shown 99.3% drug release till 24 h in a controlled manner in comparison to plain hydrogel beads, which released more than 65% of the drug before entering into the colonic region. We can conclude that coated alginate hydrogel beads containing liposome can be used as a potential carrier for colonic drug delivery.

In vitro and in vivo evaluation of an oral multiple-unit formulation for colonic delivery of insulin

A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2h of testing in 0.1N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4°C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds.

Optimization of a Novel Oral Colon Delivery System of Indomethacin Using Full Factorial Design

Purpose: To develop and optimize indomethacin (IDM) matrix tablets for specific colon drug delivery.Methods: Indomethacin matrix tablets containing hydrogenated castor oil (HCO), and pectin (PEC) were prepared by hot fusion method. A 32 full factorial design was used to investigate the combined effect of two independent formulation variables, X1 and X2, namely, the amount of HCO and PEC, respectively. Their effect on IDM release from the matrix tablets in acidic medium (0.1 N HCl) and phosphate buffer (pH 6.8), were analyzed and optimized. A contour plot was also applied to graphically represent the effect of the independent variables on drug release in pH 6.8 medium at 2 h (Y1) and 24 h (Y2), and the time required for 25 % drug release (Y3) as dependent variables.Results: The optimized IDM matrix tablets showed almost total retardation of drug release in acidic medium and prolonged sustained release in pH 6.8 medium over 24 h. The correlation coefficient (R2) value for Y1, Y2 and Y3 were 0.99850, 0.9980 and 0.9970, respectively, indicating good correlation between dependent and independent variables. Differences between the coefficients for Y1, Y2 and Y3 were significant (p &lt; 0.05), and hence contributed significantly to the prediction of the independent variables.Conclusion: The findings indicate that successful design, development, and optimization of IDM matrix tablets for colon delivery has been achieved.Keywords: Indomethacin, Hydrogenated castor oil, Pectin, Factorial design, Matrix tablets, Colondelivery system

Role of Polysaccharides in Colon-Specific Drug Delivery

Copyright © 2015, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Oral colon delivery has gained wide interest not just for the treatment of local diseases of the colon, such as inflammatory bowel disease (IBD) or Crohn’s disease, but also as a reliable approach for peptide and protein drug delivery (1). Owing to the distal location of the colon in the gastrointestinal (GI) tract, an oral colon-specific drug delivery system must withstand the conditions in the upper GI tract and should rapidly release the drug upon entry into the colon. The slow movement of material through the colon allows the presence of a large microbial population, much greater than that in the stomach or small intestine. These bacteria produce a wide range of reductive and hydrolytic enzymes, many of which are not present in the upper GI tract (2). Therefore, taking susceptibility to degradation by colonic enzymes into consideration, different natural or synthetic polymers have been employed in approaches such as prodrugs, hydrogels, matrices, and biodegradable coating materials. These polymers protect the drug from the conditions in the upper GI tract and undergo degradation via cleavage by colonic microbial enzymes, thus enabling drug release in the colon environment. A large number of polysaccharides are resistant to degradation by gastric and intestinal bacteria and are specifically hydrolyzed by colonic microbial flora; thus, they show potential for use as colon-specific drug delivery systems (3). Naturally occurring polysaccharides originate from plants (pectin, inulin and guar gum), animals (chitosan and chondroitin sulfate), algae (alginates), or bacteria (dextran). They are inexpensive, non-toxic, and have varied structures and properties. Furthermore, because of their safety and biocompatibility characteristics, these polysaccharides have also been widely used as excipients in the pharmaceutical industry. The problems typically encountered with polysaccharides are their high water solubility and poor filmforming property, which can lead to premature drug release from polysaccharide-based systems at off-target sites. Several methods have been used to overcome these obstacles. One way of decreasing the solubility of polysaccharides is to make them more water-resistant and yet enzymatically degradable by using derivatives such as calcium-bound pectin (4). The other approaches are based on combining polysaccharides with other insoluble film-forming polymers that limit the hydration of polysaccharides and thus inhibit premature drug release. In this respect, various polymers such as ethyl cellulose and polymethacrylates (5) have been used. The formation of polyelectrolyte complexes with an anionic (pectin) and a cationic polysaccharide (chitosan) was successfully assessed (6). Most recently, a combination of a polysaccharide-based system and the other colonic delivery systems such as pHand time-dependent polymers have been the broad direction of interest because of the significant advantages of site-specificity of drug release in the colon. and owing to the various benefits of naturally occurring polysaccharides.

Development of enoxaparin sodium polymeric microparticles for colon-specific delivery.

Background and aimsRecent studies have shown that low molecular weight heparins are effective in the treatment of inflammatory bowel disease. Therefore, there is considerable interest in the development of an oral colonic delivery pharmaceutical system allowing targeted release of heparin in the inflamed tissue. The objective of this study was to prepare microparticles for the oral administration and colonic release of enoxaparin and to evaluate the influence of certain formulation factors on their characteristics.MethodsMicroparticles were prepared by water/oil/water double emulsion technique followed by solvent evaporation. The influence of several formulation factors on the characteristics of microparticles were evaluated. The formulation factors were alginate concentration in the inner aqueous phase, polymer (Eudragit® FS 30D and Eudragit® RS PO) concentration in the organic phase and ratios between the two polymers. The microparticles were characterized in terms of morphology, size, entrapment efficiency and enoxaparin release.ResultsThe results showed that increasing sodium alginate percentage reduced the encapsulation efficiency of enoxaparin and accelerated enoxaparin release. Regarding the influence of the two polymers, reducing polymer concentration in the organic phase led to a smaller size of microparticles, a lower entrapment efficiency and an important retardation of enoxaparin release. The formulation prepared with Eudragit® FS 30D limited the release to a maximum of 3% in gastric simulated environment, a specific characteristic of oral systems for colonic delivery, and fulfilled our objective to delay the release.ConclusionsMicroparticles prepared with Eudragit® FS 30D represent a suitable and potential oral system for the colonic delivery of enoxaparin.

Film coatings for oral colon delivery

Oral colon delivery is pursued through a number of formulation strategies with the aim of enabling effective and well-tolerated treatments for large bowel pathologies or enhancing the intestinal absorption of peptide and protein drugs. According to such strategies, coated dosage forms for colonic release may be provided with microbiota, pH, pressure or time-dependent polymeric films. Microbiota-activated coatings are mostly obtained from polysaccharides of natural origin mixed with insoluble structuring excipients. Alternatively, synthetic azo compounds have been employed, generally requiring organic solvents for use as spray-coating agents. On the other hand, pH-sensitive films show responsiveness to pH changes in the lower gut, such as the rise generally observed in the terminal ileum and distal colon or the slight acidification of caecal contents by bacterial fermentation products. Pressure-sensitive coatings are intended for rupturing because of the relatively elevated pressure that may affect solid dosage forms in the large bowel. Finally, time-dependent films are expected to undergo timed erosion, break-up or permeabilization processes irrespective of the aforementioned physiological variables. In this review, the differing films applied for colon delivery purposes are surveyed, and details on their composition, manufacturing and performance are reported.

Colon-targeted quercetin delivery using natural polymer to enhance its bioavailability

The aim of the present study is to develop a polymer (Guar Gum)-based matrix tablet (using quercetin as a model drug) with sufficient mechanical strength, and promising in vitro mouth-to-colon release profile. By definition, an oral colonic delivery system should retard drug release in the stomach and small intestine, and allow complete release in the colon. By drug delivery to the colon would therefore ensure direct treatment at the disease site, lower dosing, and fewer systemic side effects. Quercetin is antioxidant in nature and used to treat colon cancer, but they have poor absorption in the upper part of the gastrointestinal tract (GIT). As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time, and an increased responsiveness to absorption enhancers. By achieving a colon-targeted drug delivery system, the absorption of quercetin may be increased, which leads to better bioactivity in fewer doses.