Colon-targeted Tablets Research Articles

3D Printed Personalized Colon-targeted Tablets: A Novel Approach in Ulcerative Colitis Management.

Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life.

Formulation and Characterization of Simvastatin-Loaded Nanosponges: An Innovative Technique for Colon-Targeted Drug Delivery

Background:: To enhance the solubility of simvastatin by improving the surface area of the drug particle by preparing nanosponges that are enclosed in a tablet and capsule oral solid dosage forms, which in turn helps maintain the drug's stability. Objective:: The present investigation aimed to develop a simvastatin nanosponge containing Eu-dragit as a polymer with different ratios of drug-to-polymer concentration to increase its solubility and further improve the oral bioavailability by using nanosponges’ formulation technique. Methods:: The emulsion solvent diffusion method was used to prepare simvastatin nanosponges by using Eudragit S 100, Eudragit L 100, and a combination of both in different drug-to-polymer ratios, i.e., 1:0.5, 1:1, 1:1.5, and 1:2. To characterize the conductivity, molecular changes, and size of the prepared nanosponges, a variety of evaluation parameters, including the compressibil-ity index, Hausner's ratio, angle of repose, microscopy, production yield, entrapment efficiency, drug content, in vitro drug release studies, DSC, XRD, FTIR, and SEM were evaluated. Opti-mized formulation was used to prepare colon-targeted tablets and capsules by taking nanosponges equivalent to 20 mg of simvastatin. Results:: The percentage yield, drug content, and entrapment efficiency of the final formulation were observed at 81 ± 0.26%, 92.4%, and 97 ± 0.56%, respectively. The in vitro drug release of the optimized formulations was 91.42 % at 12 hrs. The drug release followed the Peppas model with a super case II transport mechanism. Conclusion:: The use of the nanosponge delivery system increased the solubility of simvastatin seven times, which in turn increased the drug's bioavailability.

Quality by Design Approach for Optimization of Microbial and pH-Triggered Colon-Targeted Tablet Formulation Using Carboxymethyl Tamarind Gum.

ABSTRACT The purpose of this study was to apply the quality by design (QbD) approach in the development of a microbial and pH-triggered colon-targeted budesonide tablet. A retrospective research strategy was used to select various polysaccharide-based natural gums such as tamarind gum, gellan gum, karaya gum, gum ghutti, and khaya gum, which were then evaluated for their effectiveness in microbial degradation and targeting the colon. Viscosity profiles were generated in the presence of a prebiotic culture medium prepared by using the Velgut capsule that mimicked the impact of 4% rat cecal content and helpful in screening of natural polymer. Based on the cumulative drug release data of preliminary batches, carboxymethyl (CM) tamarind gum was identified as a superior and an excellent polymer over the tamarind gum for formulation development. The presence of water as a bridging agent in wet granulation also played an important role in the retardation of drug release. Tablets were supercoated with the enteric polymer, Eudragit S100. The Box-Behnken design was utilized, where the selected independent variables were the proportion of CM tamarind gum, % water proportion, and % weight gain of Eudragit S 100 to optimize the formulation. The optimized design space was generated with the criteria that a drug release should be of less than 5% within the first 2 h, less than 10% within the first 5 h, and more than 70% within the first 8 h, to achieve colon targeting. The optimized batch F3 was found stable as per International Council for Harmonisation guidelines. The roentgenography study for optimized formulation demonstrated that it remained intact for 5 h and, at 7 h, was disseminated completely. CM tamarind gum is efficient for colon targeting, and its proportion in 100 mg along with an enteric coating of 6% led to the optimized formulation.

Formulation Development and Characterization of Vancomycin Hydrochloride Colon-Targeted Tablets Using In-Situ Polyelectrolyte Complexation Technique

Introduction: Vancomycin hydrochloride (VH) is an amphoteric glycopeptide antibiotic used to manage enterocolitis and pseudomembranous colitis. However, VH is prone to proteolytic degradation in the stomach, thus obscuring the drug entry into the colon. Colon-targeted drug delivery can prevent gastric degradation and localise the drug in the colon. 
 Methodology: The applicability of in situ polyelectrolyte complexation technique using the polymers Chitosan, Karaya gum, and Hupu gum at various concentrations along with enteric coating using Eudragit S100 was studied for the preparation of colon-targeted tablets of VH.
 Colon-targeted tablets of VH are developed by incorporating natural polymers like chitosan, karaya gum, and hupu gum at different concentrations such that in-situ polyelectrolyte complex is formed and the formulations were then coated with Eudragit S100(6%, 8%, and 10% weight gain) to release the drug in a controlled manner in the colon. 
 Results: Prepared formulations were subjected to in vitro, ex vivo, and in vivo evaluation studies. Out of all the prepared formulations, the formulation H2C10 prepared with 10:2 PEC and 10% Eudragit S100 coating has shown a sufficient lag time of 2 hours in 0.1N HCl, 3 hours of lag time in pH 6.8 phosphate buffer and has shown a 100.02% drug release at 22 hours in pH 7.4 phosphate buffer. 
 Conclusion: The research results suggested that a colon-targeted drug delivery system of VH can decrease drug degradation and achieve higher concentrations in the colon to provide more therapeutic benefits.

Formulation and evaluation of 5-fluorouracil controlled release chronotherapeutic drug delivery system (CTDDS) for colorectal cancer

Objective: As most of the drugs disintegrate and dissolve in stomach before reaching the target site and to substitute intravenous (IV) route based chrono modulated chemotherapy, oral colon target drug delivery system was formed. The aim of this study was to design, develop, and evaluate a colon targeted tablet containing 5-Fluorouracil (5-FU) to give a controlled release effect of drug for colonic cancer with a goal to increase the bioavailability and improve the patient compliance. Methods: Varied concentration of different polymers such as Xanthan gum and Eudragit were used to get an optimized formulation of 5-FU tablet. The prepared formulation was evaluated for pre compression and post compression parameters such as hardness, weight, friability and drug content uniformity. The optimized formulation was further evaluated by Fourier Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), in-vitro dissolution studies, dissolution kinetic modeling and stability analysis. Results: All pre-formulation tests were within range of USP standards. Friability of all tablets was satisfied. The interference of the polymers was ruled out by FTIR. In-vitro release studies of 5-FU tablets in phosphate buffer of pH 7.0 were performed using a modified diffusion cell that resulted sustained release (90.99% to 92.69% after 12h) and kinetic models depicted the combined diffusion and dissolution mechanism of release. The optimized tablets were found having only physical interactions based on DSC. The product was found stable when evaluated using accelerated stability studies. Conclusion: It was concluded from the studies that the colon target tablet of 5-FU prepared by different concentration of polymers were optimized and can be efficiently used to control the rate of drug release to the colon in the belief of improved therapeutic efficacy and tolerability. Therefore, it is a better alternative for intravenous route based chrono modulated chemotherapy.

Design, Formulation, Optimization and In-vitro Evaluation of Colon-targeted Tablet Utilizing Polymer Isolated from Artocarpus heterophyllus

Objective: The objective of the present study is to formulate, optimize, and evaluate the colon-targeted oral Tablet by utilizing the polymer obtained from Artocarpus heterophyllus. Ibuprofen was used as a model drug in the study. Methods: The Polymer was extracted from the fresh fruits of Artocarpus heterophyllus and subjected to identification and characterization. The formula of the Tablet was optimized using 3 factors 3 levels Box-Behnken design (Design Expert Software). The colon-targeted Tablets were then formulated and coated with pH-dependent polymer to avoid release in the upper gastrointestinal tract. Results: Pre-compression and post-compression characteristics of the Tablet were studied which were within the standard limits.

3D printed tablets containing oxaliplatin loaded alginate nanoparticles for colon cancer targeted delivery. An in vitro/in vivo study.

This study aimed to develop a colon-targeted tablet of oxaliplatin (OP) using the combination of nanotechnology and fused deposition modeling (FDM) 3D printing to improve its antitumor activity, tumor targetability, and safety profile. Eudragit L100-55 filament containing OP loaded alginate nanoparticles (OP-NPs) were fabricated using hot-melt extrusion method and printed by an FDM printer to 3D printed tablets with good uniformity in the drug content and selective release of OP in the colonic environment. The antitumor effect of 3D printed tablets containing OP-NPs in CT-26 tumor-bearing mice was evaluated compared to intravenous and oral administration of OP solution, and compressed tablets containing OP-NPs, which were prepared by direct compression method with the same formulation. The antitumor effect of 3D printed tablets containing OP-NPs was remarkable and comparable with intravenous OP solution (p˃0.05) with a better safety profile, whereas compressed tablets did not show any significant antitumor effect, probably in terms of non-selective drug release in stomach and upper intestine environments. This study highlights the potential of the combination of nanotechnology and 3D printing in the preparation of colon-specific drug delivery systems of chemotherapeutic drugs with good antitumor activity, tumor targetability, and safety profile for colorectal cancer treatment.

FORMULATION AND IN VITRO EVALUATION OF RAMELTEON TABLETS FOR COLON DRUG DELIVERY SYSTEM BY COMPRESSION COATING

Objective: Ramelteon, is a sleep agent that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABAA receptors. In the present research work, the formulation of ramelteon targeted to colon by using various polymers developed.
 Methods: Colon-targeted tablets were prepared in two steps. Initially, core tablets were prepared and then the tablets were coated by using different pH dependent polymers. Ethylcellulose, Eudragit RLPO and L100 were used as enteric coating polymers. The precompression blend of all formulations was subjected to various flow property tests and all the formulations were passed the tests. The tablets were coated by using polymers and the coated tablets were subjected to physical characterization, drug content, in vitro drug release and kinetics of drug release.
 Results: Among all the formulations, F4 formulation was found to be optimized as it was retarded the drug release up to 18 h and showed maximum of 99.25% drug release. It followed the first-order kinetics mechanism. All the formulations having Korsmeyer-Peppas ‘n’ values are in the range of 0.540 to 0.818. Hence, it was concluded that the prepared formulations followed non-Fickian diffusion.
 Conclusion: An effective and stable remelteon colon targeted formulation developed for treating insomnia.

Development and In Vitro Evaluation of a Novel Pulsatile Drug Delivery System Containing Dexketoprofen Trometamol

A pulsatile drug delivery system containing dexketoprofen trometamol was designed by combining immediate release and colon-targeted mini tablets into a capsule. Both immediate release and colon-targeted mini tablets were prepared by wet granulation. Furthermore, colon-targeted mini tablets were coated with Eudragit L 100, Eudragit S 100, Eudragit RS 30D, and ethylcellulose (Surelease®) using Wurster and pan coating methods. The optimum drug release of the system developed in the study was found to be mini tablets coated with 30% Eudragit S 100 on a 20% Surelease® subcoating for the purpose of colon targeting. In the finished product, the immediate release part released the drug within the first hour, and less than 5% release was observed from the colon-targeted tablets in a 0.1 N HCl in 2 h. Then, less than 20% release occurred in the colon-targeted tablets up to 6 h in pH 6.8 phosphate buffer solution. The cumulative release rate reached 100% for up to 12 h. To our knowledge, it was the first time dexketoprofen trometamol was designed by combining both immediate release and colon-targeted mini tablets in a one dosage form.

FORMULATION AND EVALUATION OF PH-DEPENDENT COLON-TARGETED TABLETS OF RIFAXIMIN BY DESIGN OF EXPERIMENT

Objective: The research is designed at formulating and evaluating pH-sensitive rifaximin colon-targeted tablets for targeted action in proximal colon.
 Method: The colon-targeted tablets are done by granulation of three levels of polymers such as Eudragit L30D, Carbopol 974P, and ethyl cellulose. The evaluation parameters such as swelling studies, drug dissolution, in vitro drug release studies, stability, and the Fourier transform infrared studies carried out for optimized formulations.
 Results: Physicochemical parameters of all the 27 formulations (RF1-RF27) evaluated and RF21 is chosen for further investigation based on weight variation, hardness, drug content, and swelling index. The in vitro drug release studies indicate that the optimized formulation RF21 released 98.75% drug within 24 h. The stability studies indicate that the formulation is stable.
 Conclusion: An effective and stable pH-dependent rifaximin colon-targeted tablet formulated for the targeted treatment of bowel syndrome.

Development and In Vivo Evaluation of Mesalazine Colon Targeted Tablets

The main objective of the present study was to develop colon-targeted tablets of mesalazine by wet granulation method using 33 Response surface method with design of experiment software and HPMC K4M, Eudragit RL100, Ethyl cellulose and PVP K-30 used as pH dependent polymers. All the formulations (F1 to F27) were evaluated for the physicochemical parameters and were subjected to in vitro drug release studies. The amount of Mesalazine released from tablets at different time intervals was estimated by UV spectrophotometer. The formulation F26 released 98.16 % of mesalazine after 24 h, whereas marketed product drug release was 92.02 ± 2.15 after 24 h. From in vivo bioavailability studies, after oral administration of colon targeted tablet containing 400 mg mesalazine, the Cmax, Tmax, and AUC0–∞ of optimized formulation and marketed product was found to be 683.21 ± 0.03 ng/mL, 6.01 ± 0.04 h, 4150.12 ± 5.12 ng*h/mL and 445.34 ± 3.22 ng/mL, 4.00 ± 0.01 h, 3457.18 ± 5.32 ng*h/mL respectively. Cmax, Tmax and AUC values of optimized formulation were found to be significantly higher than of marketed product. The pH dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of mesalazine for the treatment of disease at colon region.

Preparation of Colon-Targeted Acetylharpagide Tablets and its Release Properties in vivo and in vitro.

Ethno Pharmacological Relevance: Acetylharpagide is a monomeric compound extracted from Ajuga decumbens, widely used for remedying infectious and inflammatory diseases in Southern China.Aim of the Study: The present study designed and investigated the formulation of colon-targeted acetylharpagide tablets according to the dual controlled release mechanisms of time-delay and pH-sensitivity.Materials and Methods: The core tablets of acetylharpagide were coated with the material used in time-delay systems such as ethyl cellulose and suitable channeling agent, followed by pH-dependent polymers, polyacrylic resin II and III in a combination of 1:4. Furthermore, the release and absorption performance of colon-targets tables were evaluated in vitro and in vivo. In the in vitro tests, the optimized formulation was not released in simulated gastric fluid in 2 h; the release was <5% at pH 6.8 simulated intestinal fluids for 4 h; the drug was completely released within 5 h at pH 7.6 simulated colon fluid. In the in vivo tests, pharmacokinetic characteristics of the colon-targeted tablets were investigated in dogs.Results: The results indicated that the acetylharpagide tablets with the technology of colon-targeting caused delayed Tmax, prolonged absorption time, lower Cmax, and AUCINF_obs. Meanwhile, the apparent volume of distribution (Vz_F_bs) of the colon-target tablets was higher than the reference.Conclusions: These results suggested that colon-targeted acetylharpagide tablets deliver the drug to the colon. The in vitro performance of colon-targeted acetylharpagide tablet was appropriately correlated with its performance in vivo.

Design and preparation of a novel colon-targeted tablet of hydrocortisone

Design and preparation of a novel colon-targeted tablet of hydrocortisone

Design and preparation of a novel colon-targeted tablet of hydrocortisone

ABSTRACT The objective of this research was to design a new colon-targeted drug delivery system based on chitosan. The properties of the films were studied to obtain useful information about the possible applications of composite films. The composite films were used in a bilayer system to investigate their feasibility as coating materials. Tensile strength, swelling degree, solubility, biodegradation degree, Fourier transform infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning electron microscope (SEM) investigations showed that the composite film was formed when chitosan and gelatin were jointly reacted jointly. The results showed that a 6:4 blend ratio was the optimal chitosan/gelatin blend ratio. In vitro drug release results indicated that the Eudragit- and chitosan/gelatin-bilayer coating system prevented drug release in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). However, the drug release from a bilayer-coated tablet in SCF increased over time, and the drug was almost completely released after 24 h. Overall, colon-targeted drug delivery was achieved by using a chitosan/gelatin complex film and a multilayer coating system.

In Vitro and In Vivo Correlation of Colon-Targeted Compression-Coated Tablets.

This study was performed to assess and correlate in vitro drug release with in vivo absorption of prednisolone (PDL) from a colon-targeted tablet prepared by compression coating of core tablet. In vivo drug absorption study was conducted using a high performance liquid chromatographic (HPLC) method, which was developed and validated for the estimation of PDL in rabbit plasma. The calibration curve showed linearity in the concentration range of 0.05 to 50 μg/mL with the correlation coefficient (r) of 0.999. The method was specific and sensitive with the limit of detection (LOD) and lower limit of quantification (LLOQ) of 31.89 ± 1.10 ng/mL and 96.63 ± 3.32 ng/mL, respectively. The extraction recovery (ER) of PDL from three different levels of quality control (QC) samples ranged from 98.18% to 103.54%. In vitro drug release study revealed that less than 10% drug was released in 6.34 h and almost complete (98.64%) drug release was achieved in the following 6 h. In vivo drug absorption study demonstrated lower values of C max, AUCtotal, and protracted T max from compression-coated tablet. The results confirmed the maximum release of drug in the colon while minimizing release in the upper gastrointestinal tract (GIT). An excellent in vitro and in vivo correlation (IVIVC) was also achieved after considering the lag time.

Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets

Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33±0.06%) in the initial lag period followed by progressive release (100.78±0.64%) for 24h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67ng/ml at T max 10h, where as in case of immediate release tablets the C max was 15,677.52ng/ml at T max 3h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery.

Present research efforts are focused in developing compression-coated ketorolac tromethamine tablets to improve the drug levels in colon by retarding the drug release in the stomach and small intestine. To achieve this objective, core tablets containing ketorolac tromethamine were prepared by direct compression and compression coated with sodium alginate. The developed tablets were evaluated for physical properties, in vitro drug release, X-ray imaging, and pharmacokinetic studies in human volunteers. Based on the in vitro drug release study, the optimized formulation showed very little drug release (6.75 ± 0.49%) in the initial lag period of 5h, followed by progressive release up to 97.47 ± 0.93% within 24h. The X-ray imaging of tablets in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. From the pharmacokinetic study, the C max of colon-targeted tablets was 3,486.70ng/ml at T max 10h, whereas in the case of immediate-release tablets, the C max of 4,506.31ng/ml at T max 2h signifies the ability of compression-coated tablets to target the colon. In conclusion, compression-coated tablets are suitable to deliver ketorolac tromethamine to the colon.

Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets

Objective: The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine.Methods: KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro–in vivo correlation.Results and discussions:From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (Cmax) was 4482.74 ng/ml at 2 h Tmax and colon-targeted tablets showed Cmax = 3562.67 ng/ml at 10 h Tmax. The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively.Conclusion: Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.

Ronidazole pharmacokinetics in cats following delivery of a delayed‐release guar gum formulation

Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum-coated colon-targeted tablets of RDZ and to determine the pharmacokinetics of this delayed-release formulation in cats. Guar gum-coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum-coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady-state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.

Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet

The work was aimed at developing calcium-pectinate matrix tablet for colon-targeted delivery of meloxicam (MLX) microsponges. Modified quassi-emulsion solvent diffusion method was used to formulate microsponges (MS), based on 32 full factorial design. The effects of volume of dichloromethane and EudragitRS100 content (independent variables) were determined on the particle size, entrapment efficiency and %cumulative drug release of MS1–MS9. The optimized formulation, MS5 (dmean=44.47μm, %EE=98.73, %CDR=97.32 and followed zero order release) was developed into colon-targeted matrix tablet using calcium pectinate as the matrix. The optimized colon-targeted tablet (MS5T2) shielded MLX loaded microsponges in gastrointestinal region and selectively delivered them to colon, as vizualized by vivo fluoroscopy in rabbits. The pharmacokinetic evaluation of MS5T2 in rabbits, revealed appearance of drug appeared in plasma after a lag time of 7h; a tmax of 30h with Fr=61.047%, thus presenting a formulation suitable for targeted colonic delivery. CLSM studies provided an evidence for colonic luminal retentive ability of microsponges at the end of 8h upon oral administration of MS5T2. Thus calcium pectinate matrix tablet loaded with MLX microsponges was developed as a promising system for the colon-specific delivery that has potential for use as an adjuvant therapy for colorectal cancer.