Colon-specific Drug Delivery System Research Articles

Applicability of enzyme-responsive mesoporous silica supports capped with bridged silsesquioxane for colon-specific drug delivery

The necessity and advantages of colon-specific drug delivery systems have been well recognized and documented. In this study, we prepared a new capped mesoporous silica nanoparticle as a potential material for colon-specific drug delivery. This material consisted of nanoscopic mesoporous MCM-41 supports loaded with ibuprofen and capped with a bridged silsesquioxane with azo groups. X-ray diffraction, N2 sorption analysis, transmission electron microscopy, UV–vis diffusion reflectance spectroscopy, and 29Si magic angle spinning nuclear magnetic resonance were used to verify the well-ordered mesostructure and the successful grafting of bridged silsesquioxane on the surface of the mesoporous material. The material showed “zero release” in simulated gastric fluid and simulated intestinal fluid. The opening and release of cargo occurred in simulated colonic fluid with azo-reductase due to the reductive cleavage of the azo bonds. However, no release of ibuprofen was observed in phosphate-buffered saline without enzyme. These results indicated that the capped mesoporous material showed excellent behavior for colon specificity and could be a potential material for colon-specific drug delivery.

Impact of cross-linking and drying method on drug delivery performance of casein-pectin microparticles.

Pectin is a heteropolysaccharide which has been investigated for the development of colon-specific drug delivery systems. Polymers have been associated with pectin to reduce its aqueous solubility and improve the performance of drug delivery systems. Pectin-casein interaction is widely known in food research, but it has not been fully considered by pharmaceutical scientists. Thus, this study investigated the potential of casein-pectin microparticles as a drug delivery system and clarified the impact of cross-linking and drying methods on the in vitro release of indomethacin (IND) or acetaminophen (PCT) from microparticles. Microparticles were prepared by coacervation and dried by spray or spouted bed methods. Drug recovery, in vitro drug release, size, morphology, and the thermal and diffractometric properties of dried microparticles were determined. Spray-dried non-cross-linked microparticles were able to prolong IND release, and pectin was still degraded by pectinolytic enzymes. On the other hand, glutaraldehyde cross-linking prevented the enzymatic breakdown of pectin without improving IND release. Spouted bed drying reduced IND recovery from all microparticles when compared with spray drying, thus the successful spouted bed drying of microparticles depends on the chemical characteristics of both the drug and the polymer. Release data from PCT microparticles suggested that the microparticle formulation should be improved to bring about a more efficient delivery of water-soluble drugs. In conclusion, casein-pectin microparticles show great potential as a drug delivery system because casein reduces the water solubility of pectin. The drying method and cross-linking process had significant effects on the in vitro performance of these microparticles.

Influence of Beta-cyclodextrin and Chitosan in the Formulation of a Colon-Specific Drug Delivery System

The increase in diseases of the colon underscores the need to develop cost-effective site-directed therapies. We formulated a polysaccharide-based matrix system that could release ibuprofen under conditions simulating those in the colon by employing a wet granulation method. Tablets were prepared in a series of formulations containing a polysaccharide (beta-cyclodextrin and chitosan) matrix system along with ethylcellulose. We characterized physicochemical properties and performed an in vitro drug release assay in the absence and presence of digestive enzymes to assess the ability of the polysaccharides to function as a protective barrier against the upper gastrointestinal environment. Fourier transform infrared spectroscopy studies revealed no chemical interaction between ibuprofen and polysaccharides; however, spectrum analysis suggested the formation of an inclusion complex of beta-cyclodextrin with ibuprofen. The formulations contained 50% ethylcellulose and 50% beta-cyclodextrins (1:1) were proven to be the better formulation that slowly released the drug until 24 h (101.04 ± 0.65% maximum drug release in which 83.08 ± 0.89% drug was released in colonic medium) showed better drug release profiles than the formulations containing chitosan. We conclude that a beta-cyclodextrin drug carrier system may represent an effective approach for treatment of diseases of the colon.

Combination of Pectin and Eudargit RS and Eudragit RL in the Matrix of Pellets Prepared by Extrusion - Spheronization for Possible Colonic Delivery of 5-Amino Salicylic Acid

Background: Different methods have been studied for targeting drugs to the colon, such as pH-based, time dependent and bacterially degradable systems. However, due to variations in physiological conditions of patients, one system alone could not be completely reliable on colonic drug delivery. Objectives: The aim of this study was preparation and evaluation of a novel colon-specific drug delivery system for 5-ASA (mesalazine) pellets using pectin as a microbially degradable polymeric carrier and Eudragit RS (ERS) and Eudragit RL (ERL) as time-dependent polymers. Materials and Methods: Formulations were constructed based on a multilevel full factorial design. Pellets were prepared via extrusion - spheronization and evaluated for physicochemical properties, image analysis, SEM, FT-IR, DSC and in vitro drug release studies in the simulated gastric fluid with pH = 1.2 (SGF), simulated intestinal fluid with pH = 6.8 (SIF) and simulated colonic fluid with pH = 6.8 in presence of pectinolytic enzyme (SCF). Results: It was shown that in the presence of pectin, formulations without ERL had a relative resistance to drug release in SGF. Pellets containing pectin and the least amount of ERS had the highest burst release effect in SCF. On the other hand, increasing in amount of ERS in the formulations caused a sustained drug release. Presence of pectin in formulations containing ERS and ERL caused sensitivity of formulations to pectinolytic enzyme which can suitable for a colon specific drug delivery system. Conclusions: It was shown that combination of pectin and eudragits can relatively control drug release in the upper GI. On the other hand, pectin degraded in the presence of pectinase and formulations were susceptible to the colonic media.

Combination of Pectin and Eudargit RS and Eudragit RL in the Matrix of Pellets Prepared by Extrusion-Spheronization for Possible Colonic Delivery of 5-Amino Salicylic Acid

Different methods have been studied for targeting drugs to the colon, such as pH-based, time dependent and bacterially degradable systems. However, due to variations in physiological conditions of patients, one system alone could not be completely reliable on colonic drug delivery. The aim of this study was preparation and evaluation of a novel colon-specific drug delivery system for 5-ASA (mesalazine) pellets using pectin as a microbially degradable polymeric carrier and Eudragit RS (ERS) and Eudragit RL (ERL) as time-dependent polymers. Formulations were constructed based on a multilevel full factorial design. Pellets were prepared via extrusion - spheronization and evaluated for physicochemical properties, image analysis, SEM, FT-IR, DSC and in vitro drug release studies in the simulated gastric fluid with pH = 1.2 (SGF), simulated intestinal fluid with pH = 6.8 (SIF) and simulated colonic fluid with pH = 6.8 in presence of pectinolytic enzyme (SCF). It was shown that in the presence of pectin, formulations without ERL had a relative resistance to drug release in SGF. Pellets containing pectin and the least amount of ERS had the highest burst release effect in SCF. On the other hand, increasing in amount of ERS in the formulations caused a sustained drug release. Presence of pectin in formulations containing ERS and ERL caused sensitivity of formulations to pectinolytic enzyme which can suitable for a colon specific drug delivery system. It was shown that combination of pectin and eudragits can relatively control drug release in the upper GI. On the other hand, pectin degraded in the presence of pectinase and formulations were susceptible to the colonic media.

Modified Pulsincap of Ibuprofen - A Novel Approach for Chronotherapy

The aim of the present work was to develop colon specific drug delivery system for ibuprofen using natural polymers as carriers. We have investigated colon specific, pulsatile device to achieve time and site specific release of ibuprofen based on chronopharmaceutical considerations. The basic design consists of an insoluble hard gelatin capsule body, filled with ibuprofen surface solid dispersions and sealed with guar gum hydrogel plug. The entire capsule was coated with ethyl cellulose, so that the variability in gastric emptying time can be overcome and a colon specific release can be achieved. Surface solid dispersions (SSDs) of ibuprofen were prepared using natural polymers such as Guar gum (GG), Hupu gum (HG) and Xanthan gum (XG) in the weight ratios of 1:0.5, 1:1 and 1:2 by using solvent evaporation method. Physicochemical properties of the prepared SSD were characterized by FTIR and DSC. Optimized SSD were obtained by practical yield, drug content, solubility and dissolution studies and were selected for further fabrication of pulsincaps. Guar gum was used as hydrogel plug material to maintain a suitable lag period. The prepared pulsincaps were evaluated for in-vitro release. Pulsincap formulated with Ibuprofen-Hupu gum (PF3) at 1:2 ratio of surface solid dispersions showed highest drug release over the period of 12 hr and release was found to be Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of ibuprofen is a suitable device for the time dependent and site specific delivery to the colon segment of GIT.

Design and development of liposomes for colon targeted drug delivery

Background: Local delivery to bowel tissue through oral administration is a challenging but a desirable goal to treat diseases like inflammatory bowel disease (IBD). Colon specific drug delivery system should be capable of protecting the drug en route colon.Purpose: Liposomes have shown potential to specific accumulation at inflammation site thus reduce toxicity; hence it can be used for effective treatment of IBD. Methods: Liposomes prepared using thin film hydration method. Statistical design was used for optimization. Colitis was induced using acetic acid. Inverted sac method was used as ex vivo model for IBD. Myeloperoxidase (MPO) activity and histopathology comparative study was carried out. Liposomes were formulated in enteric coated capsules to deliver the liposome specifically in initial segment of colon.Results: Particle size and entrapment efficiency were between 200 and 300 nm and 40 and 60%, respectively. In vivo and ex vivo study indicates higher accumulation of liposomes in colonic region as compared to pure drug. Enteric coated capsules delivered the drug after 5 h lag time.Discussion: Low particle size is attributed to low lipid content and stabilization due to surfactant. At higher cholesterol level, vesicles cannot reshuffle into smaller vesicles due to rigidization. Study shows higher accumulation of liposomes due to its lipoidal nature as compared to pure drug due to membrane transfer mechanism of drug thus MPO significantly lowers as compared to standard group (p < 0.05).Conclusions: Higher accumulation of liposomal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease.

Formulation and Evaluation of Colon Targeted Drug Delivery System of Levetiracetam using Pectin as Polymeric Carrier

Article history: Received on: 10/12/2012 Revised on: 29/12/2012 Accepted on: 15/01/2013 Available online: 28/01/2013 The aim of the present work was to develop and evaluate colon specific sustained release tablet using levetiracetam (LEV), microbially degradable polymeric carrier (pectin), coating material and matrix forming polymers. The colon targeted tablet was prepared by wet granulation technique using different percentage of pectin as matrix carrier, starch mucilage as a binding agent, HPMC K-100 as swellable polymer and coated with Eudragit polymers. Pectin, drug and physical mixture were evaluated for incompatibility study by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). All the batches of matrix tablet (F1-F4) were subjected for in-vitro dissolution in various simulated gastric fluids for suitability for colon specific drug delivery system. Tablets were evaluated for micromeritic properties of granules, physical properties, drug content, water uptake and erosion characteristics. F2 was optimized and subjected to coating based on evaluation results. The dissolution study of F2 revealed, in simulated intestinal fluid (SIF) release was 40.48% at the end of 6h and in simulated colonic fluids (rat caecal content) was 102.88% after degradation at the end of 8h. The colon targeted matrix tablet of LEV showed no change either in physical appearance, drug content or dissolution pattern after performing stability study for 3 months. The studies confirmed that, the designed formulation could be used potentially for colon delivery by controlling drug release in stomach and the small intestine.

Exploiting microspheres as a therapeutic proficient doer for colon delivery: a review

Introduction: Colon-specific drug delivery systems have recently gained importance for delivering a variety of therapeutic agents via oral route. This mode offers the feasibility of treating colonic pathologies with less risk of bioburden to other organs/tissues and has been widely researched for the delivery of challenging drugs. Microspheres targeted to colon have occupied central position on drug delivery due to their small size that offers characteristic intrinsic properties attributable to the carrier.Areas covered: The present deliberation precariously covers the capacious usage of microspheres for the treatment of local colonic pathologies like colon carcinomas, inflammatory bowel disease and parasitic diseases using natural as well as synthetic carriers. The write up also encompasses clinical application of microspheres.Expert opinion: Microspheres have comprehensive potential to be marketed as the patient-friendly formulation, as it would provide direct treatment at the disease site and, consequently, lower dosing and reducing systemic side effects. Wherefore, the major obstacles in delivering drugs to the colon like the absorption and degradation pathways in the proximal part of GIT could be easily overcome, and also a range of pathologies from constipation and diarrhea to the exhaustive inflammatory bowel diseases and colon carcinoma could be cured.

CPVA Grafted Poly(sodium 4-styrene sulfonate) and Studies on its Colon Specific for Chronotherapy of Nocturnal Asthma

The paper attempted to develop a colon specific drug delivery system using CPVA grafted poly (sodium 4-styrene sulfonate)(SSS), namely CPVA-g-PSSS microsphere, loaded with theophylline (TP) for chronotherapy of nocturnal asthma. The grafted CPVA-g-PSSS microspheres were prepared by surface-initiated graft-polymerization, and their surface charges were determined by testing Zeta potential. On this basis, the adsorption property of the grafted microspheres CPVA-g-PSSS for theophylline, namely drug loading ability, was mainly investigated, and the adsorption mechanism was explored. The in vitro release behavior of the drug-loaded microspheres was also examined at different pH value and in simulated gastrointestinal fluids. The experiments show the CPVA-g-PSSS microspheres exhibit strong adsorption ability (38.5 mg/g) for TP by driving of electrostatic interaction in an acidic medium. The in vitro release behavior of the drug-loaded microspheres is highly pH-sensitive. The in vitro release in simulated gastrointestinal (GI) fluid reveals that drug does not release in the stimulated gastric fluid (pH 1), while in the simulated colonic fluid (pH 7.4), a burst release phenomenon occurs, and 52% TP is released in one hour. An excellent colon-specific drug delivery system is developed to realize a lag time of drug release in 6 h runtime of upper gastrointestinal tract, which should be consistent with the demands of chronotherapy of nocturnal asthma.

Preparation, &lt;I&gt;In Vitro&lt;/I&gt; and &lt;I&gt;In Vivo&lt;/I&gt; Evaluation of Budesonide Loaded Core/Shell Nanofibers as Oral Colonic Drug Delivery System

Budesonide (BUD) loaded ethylcellulose (EC)-core/Eudragit S100-shell nanofibers (BUD-core/shell-NFs) have been successfully prepared using a coaxial electrospinning technique. The drug encapsulation efficiency was 90.48%. SEM and TEM analysis showed that fine core-shell structured nanofibers with an average diameter 190 nm and uniform core diameters 74 nm were prepared. The BUD-loaded Eudragit S100/EC composite nanofibers (BUD-NFs) were prepared using a blend electrospinning method and used as a control. In vitro release tests in HCl 0.1 N, phosphate buffer solutions pH 6.8 and 7.4 were studied. Moreover, the colon-specific characteristics were directly proven in vivo by the content of BUD in different segments of the gastrointestinal (GI) tract in rats after oral administration. Taken together, the results confirmed that BUD-core/shell-NFs had desired pH-dependent drug release profile, displayed a sustained and complete drug release in the colon, as well as protected BUD from being released completely in the upper portion of the GI tract. Compared with BUD-NFs, the BUD-core/shell-NFs have much better potential to be developed as oral colon-specific drug delivery system (OCDDS) to overcome the disadvantages of current oral formulations of BUD.

Colon Targeted Drug Delivery System ? A Novel Perspective

In the recent years there is new development in field of colon specific drug delivery system. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Crohn’s disease, ulcerative colitis, etc. but also for the systemic delivery of proteins, therapeutic peptides, anti-asthmatic drugs, antihypertensive drugs and anti-diabetic agents. New systems and technologies have been developed for colon targeting and to overcome pervious method’s limitations. Colon targeting holds a great potential and still need more innovative work. This review article discusses introduction of colon, need and approaches of colonic drug delivery, factor effecting colonic transition, colonic diseases and the novel and emerging technologies for colon targeting.

Preparation of grafted microspheres CPVA-g-PSSS and studies on their drug-carrying and colon-specific drug delivery properties

Sodium 4-styrene sulfonate (SSS) was graft-polymerized on the surfaces of crosslinked polyvinyl alcohol (CPVA) microspheres in a manner of surface-initiated graft-polymerization by using cerium salt-hydroxyl group redox initiation system, obtaining the grafted microspheres CPVA-g-PSSS. The chemical structure and physicochemical characters of CPVA-g-PSSS microspheres were fully characterized with infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and zeta potential determination. The aim of this work is to constitute a novel colon-specific drug delivery system via molecular design by using CPVA-g-PSSS microspheres as the drug-carrying material and by taking metronidazole (MTZ) as the model drug. The drug-carrying ability and mechanism of the grafted microspheres CPVA-g-PSSS for MTZ were investigated. Finally, in-vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in an acidic medium, the grafted microspheres CPVA-g-PSSS exhibit strong adsorption ability for MTZ by driving of electrostatic interaction, and have an adsorption capacity of 112mg/g, displaying the high efficiency of drug-carrying. The in-vitro release behavior of the drug-carried microspheres is highly pH-sensitive. In the medium of pH=1, the drug-carrying microspheres do not release the drug, whereas in the medium of pH=7.4, a sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior.

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery

Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs).Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract.Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer.Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.

Drug Delivery Systems with Modified Release for Systemic and Biophase Bioavailability

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Colonic delivery of film coated meloxicam tablets using natural polysaccharide polymer mixture

Now days natural polysaccharides are extensively used for the development of solid dosage forms for delivery of drug to the colon. The objective of the present study was to develop a site-specific drug, single unit formulation allowing targeted drug release in the colon. Solid unit dosage forms were prepared using polysaccharides or synthetic polymer included xanthan gum, pectin, chitosan and Eudragit-E. Meloxicam was used as a model drug. The prepared tablets were enteric coated with Eudragit-S 100 to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The dissolution data so obtained illustrates that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using xanthan gum as binder, were unable to protect drug release under similar conditions. Solid formulations containing pectin as a binder formed time-dependent release formulations. 28% drug release was observed in the usual upper gastrointestinal tract conditions, when used in a concentration of 5.92% in the tablets.DOI: http://dx.doi.org/10.3329/icpj.v1i9.11617 International Current Pharmaceutical Journal 2012, 1(9): 264-271

In Vivo Human X-ray Investigation of Combined Polysaccharide Based Drug Delivery Systems Prepared for Colonic Delivery

The present investigation was aimed to assess the in vivo performance of combined polysaccharides based compression coated tablets for colonic delivery using X-ray study. Fast disintegrating core tablets containing barium sulphate was compression coated with guar gum (GG), locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) in the ratio 3:3:4 with a coat weight of 400mg. The developed barium sulphate coated tablet was subjected for in vivo human X-ray study. X-ray study revealed that the tablet remained intact during its transit through upper part of gastrointestinal tract. The colon arrival time was found to be between 5-8 h. The disintegration of the tablet occurred in the colon between 14 to 16 h by the microflora present in the colon. In conclusion, results of X-ray studies revealed that GG and LBG along with HPMC was found to be promising coating materials for targeting drugs specifically to the colon. Keywords: Colon specific drug delivery system, colon targeting, compression-coat, diclofenac sodium, guar gum, locust bean gum, X-ray imaging and HPMC.

Formulation Development and Characterization of Guar Gum Microspheres for Colon Delivery

In the present work, colon specific drug delivery systems have been selected, to deliver the drug locally to colon for longer period of time. Cross-linked guar gum microspheres of model drug secnidazole were prepared by emulsification method and were evaluated for size and surface morphology by SEM, encapsulation efficiency, yield, swelling study. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in the presence and absence of rat cecal contents. The marketed product was also compared for drug release profiles. The guar gum microspheres retard the release of drug in stomach but it facilitates the release of large amount of drug in the colon in the presence of rat cecal contents, as these have polysaccharides enzymes that degrade the guar gum in the colon. The release data shows that 44.4% of drug was released in the presence of rat cecal content release medium in 24 hours. Drug release data were fitted to different mathematical model to find release kinetic of drug. The stability studies were performed by storing the microspheres at different conditions of storage. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at P < 0.05.

COLON TARGETING APPROACHES: PAST, PRESENT AND FUTURE

The colon specific drug delivery system is gaining importance not only for local drug delivery of drugs but also for the systemic delivery of protein &amp; peptide drugs. Colon was considered as black-box as most of the drugs are absorbed from upper part of the GI tract. Colon targeting was aimed mainly because of less enzymatic activity and longer transit time. It also has drawbacks like less water content and presence of fecal content. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and absorption in the upper portion of the GI tract and then to be ensured controlled release in the proximal colon. The various approaches that can be exploited to target the release of drug to the colon including formulation approaches through pH sensitive system are microbial triggered systems i.e., prodrugs and polysaccharide based system, timed release system, osmotically controlled drug system, pressure dependent release system, programmed pulsatile release system and others.

A Non-Invasive, Low-Cost Study Design to Determine the Release Profile of Colon Drug Delivery Systems: A Feasibility Study

Conventional bioavailability testing of dosage forms based on plasma concentration-time graphs of two products in a two-period, crossover-design, is not applicable to topical treatment of intestinal segments. We introduce an isotope dual-label approach ((13)C- and (15)N(2)-urea) for colon drug delivery systems that can be performed in a one-day, non-invasive study-design. Four healthy volunteers took an uncoated or a ColoPulse-capsule containing (13)C-urea and an uncoated capsule containing (15)N(2)-urea. In case of colon-release (13)C-urea is fermented and (13)C detected as breath (13)CO(2). Absorbed (13)C-urea and (15)N-urea are detected in urine. C and (15)N in urine released from uncoated capsules showed a ratio of 1.01 ± 0.06. The (13)C/(15)N-recovery ratio after intake of a ColoPulse-capsule was constant and lower >12 h post-dose (median 0.22, range 0.13-0.48). The (13)C/(15)N-ratio in a single urine sample at t ≥ 12 h predicted the 24 h non-fermented fraction (13)C of <26 %. Breath (13)CO(2) indicated delayed (>3 h) release and a fermented fraction (13)C >54 %. Breath and urine (13)C and (15)N data describe the release-profile and local bioavailability of a colon delivery device. This allows non-invasive bioavailability studies for evaluation of colon-specific drug delivery systems without radioactive exposure and with increased power and strongly reduced costs.