Eudragit FS30D Research Articles

Engineering 5-flourouracil and leucovorin-loaded vesicular systems for possible colon specific delivery: In vitro evaluation and real time cell assay against HCT-116 colon cell lines

5-flourouracil (5-FU) is typically modulated with leucovorin (LEU) in clinical practice to improve clinical efficacy and patient survival rates. However, this combination has undesirable side effects and makes 5-FU more toxic. Hence, integrating a vesicular system (proniosomes) with another delivery vehicle may improve drug targeting, while resolving the aforementioned drawbacks. This study aimed to engineer 5-FU/LEU proniosomes for possible delivery to the colon. The modified slurry approach was used to create drug-loaded proniosomes (150 mg/9 g of carrier) using both water-soluble (dextrin (DEX) and lactose (LAC)) and insoluble (Neusilin FH2 (NEU)) carriers. The powdered formulations were filled into Eudragit S100 (10 %)-coated capsules or Eudragit FS 30D capsules for enteric- or colon-specific delivery. In vitro evaluations (flow properties, powder X-ray diffractometry (XRD) analysis, particle size analysis, entrapment efficiency, drug release, scanning electron microscopy (SEM), polydispersity index, Fourier transform infrared spectroscopy (FTIR), and stability studies) were performed on the formulations. An in vitro cytotoxicity test [real-time cell assay (RTCA)] against HCT-116 colon cancer cell lines was performed using the optimized formulation. In vitro evaluations showed that the nanoparticles had good physicochemical properties. RTCA studies showed sustained cell death with the formulations compared to the pure drug and placebo. The sequential drug release of the colon-targeted capsules containing 5-FU and LEU- loaded proniosomes showed negligible drug release in SGF (pH 1.2) and phosphate buffer solution (pH 6.8) (approximately 11 %) but profound drug release (>80 %) at pH 7.4. Drug-loaded proniosomes engineered for colon targeting (Eudragit S100 (10 %) capsules or Eudragit FS 30D capsules) showed good colon-specific targeting and favorable in vitro cytotoxicity profiles.

Evaluation of the Antimicrobial Activity of a Formulation Containing Ascorbic Acid and Eudragit FS 30D Microparticles for the Controlled Release of a Curcumin-Boric Acid Solid Dispersion in Turkey Poults Infected with Salmonella enteritidis: A Therapeutic Model.

The selection of components within a formulation or for treatment must stop being arbitrary and must be focused on scientific evidence that supports the inclusion of each one. Therefore, the objective of the present study was to obtain a formulation based on ascorbic acid (AA) and Eudragit FS 30D microparticles containing curcumin-boric acid (CUR-BA) considering interaction studies between the active components carried out via Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) to minimize antagonistic effects, and comprehensively and effectively treat turkey poults infected with Salmonella enteritidis (S. enteritidis). The DSC and FTIR studies clearly demonstrated the interactions between AA, BA, and CUR. Consequently, the combination of AA with CUR and/or BA should be avoided, but not CUR and BA. Furthermore, the Eudragit FS 30D microparticles containing CUR-BA (SD CUR-BA MP) showed a limited release of CUR-BA in an acidic medium, but they were released at a pH 6.8-7.0, which reduced the interactions between CUR-BA and AA. Finally, in the S. enteritidis infection model, turkey poults treated with the combination of AA and SD CUR-BA MP presented lower counts of S. enteritidis in cecal tonsils after 10 days of treatment. These results pointed out that the use of an adequate combination of AA and CUR-BA as an integral treatment of S. enteritidis infections could be a viable option to replace the indiscriminate use of antibiotics.

Formulation and evaluation of colon targeted matrix tablet of ibuprofen

The present work involves the formulation of colon targeted matrix tablet of Ibuprofen by using direct compression method. Literatures regarding, Ibuprofen tablet dosage form preparation, excipients selection, manufacturing method etc., has been collected and reviewed. In this work, selection of excipients was done based on a literature review. Excipients include Eudragit S100, Ethyl cellulose, Lactose, Talc, Magnesium stearate. Quantities of the excipients were selected performing FT-IR method which is an HIS of Fourrts India Laboratory. Preformulation studies have also been performed to study the nature of API and compatibility of API with excipients by physical observation and FT-IR studies. The result showed that API was compatible with all the excipients selected. The tablets were formulated by direct compression method using the selected excipient quantities. The formulated tablets were tested for both pre-compression parameters and post compression parameters as per requirements of standards. Pre-compression parameters such asbulk density, tapped density, compressibility index, Hausner’s ratio and compressibility index. The results obtained indicate that it has good flow property for direct compression. The formulated Ibuprofen matrix tablets were coated with enteric polymer Eudragit FS30D by pan coating method. The prepared tablets were evaluated for weight variation, hardness, thickness, friability, drug content, and disintegration time and in-vitro dissolution studies. All these parameters were found to be within the standard limits. Comparative studies of coated Ibuprofen tablets and uncoated Ibuprofen tablets are evaluated for the hardness, thickness, in-vitro dissolution studies and disintegration time. Out of six formulations, the formulation F6 showed 98.51% drug release at 24 hrs. Since it provide greater protection to the core under acidic condition while at the same time show the fastest drug release under intestinal pH. So the formulation F6 was considered as the confirmatory trial and it was subjected for stability studies up to three months of accelerated stability 400C ± 2C0, 75 %± 5 % RH and found to be within limits.

Direct cyclodextrin based powder extrusion 3D printing of budesonide loaded mini-tablets for the treatment of eosinophilic colitis in paediatric patients

The purpose of this study was to combine direct powder extrusion (DPE) 3D printing and fluid bed coating techniques to create a budesonide (BD) loaded solid oral formulations for the treatment of eosinophilic colitis (EC) in paediatric patients. The preferred medication for EC treatment is BD, which has drawbacks due to its poor water solubility and low absorption. Additionally, since commercially available medications for EC treatment are created and approved for adult patients, administering them to children sometimes requires an off-label use and an impromptu handling, which can result in therapeutic ineffectiveness. The DPE 3D approach was investigated to create Mini-Tablets (MTs) to suit the swallowing, palatability, and dose flexibility control requirements needed by paediatric patients. Additionally, DPE 3D and the inclusion of hydroxypropyl-β-cyclodextrin in the initial powder mixture allowed for an improvement in the solubility and rate of BD dissolution in aqueous medium. Then, to accomplish a site-specific drug release at the intestinal level, MTs were coated with a layer of Eudragit FS 30D, an enteric polymer responsive at pH > 7.0 values. In vitro release experiments showed that film-coated MTs were suitable in terms of size and dose, enabling potential therapeutic customization and targeted delivery of BD to the colon.

Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis.

In this study, an emulsion solvent evaporation method was used to produce Eudragit RL (ERL) nanoparticles (NPs) loaded with simvastatin (SIM) for the treatment of ulcerative colitis (UC). Accordingly, the effects of different formulation variables on the properties of NPs were evaluated using the Box-Behnken design. The optimized NPs were then coated by Eudragit FS30D (EFS30D). Drug release was studied in different physiological environments. Colitis was induced by 3% of acetic acid in rats, which received NPs of SIM (10mg/kg/day), mesalazine (150mg/kg/day), blank NPs and normal saline orally for 5days. Macroscopic histopathological evaluation and biochemical analysis, including myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the colon tissues, were carried out in this study. The optimized SIM-ERL NPs showed the particle size of 182.48 ± 4.57nm, the polydispersity index of 0.29 ± 0.12, the zeta potential of 26.45 ± 4.57mV, drug loading % of 34.64 ± 0.48, the encapsulation efficiency % of 98.68 ± 0.69, and the release efficiency % of 35.78 ± 1.37. Coating the optimized NPs with EFS30D caused an increase in particle size and a decrease in the zeta potential of NPs. The optimized SIM-EFS30D/RL NPs improved the macroscopic and histopathological scores. Also, MPO activity and MDA level were reduced significantly by NPs, as compared to the control group. Therefore, this drug delivery system can be an alternative to the previous treatments of UC.

Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine

Berberine (BBR) is currently explored in the oral treatment of many disorders, especially in those involving inflammatory processes. Nanotechnology-based drug delivery systems are emerging as an effective approach for improving the poor oral absorption/bioavailability of BBR. To optimize the BBR immunoregulatory effects on a specific part of the gastrointestinal tract, here we describe a micro- and nanoencapsulated hybrid delivery system (MNEHDS) for colon-targeted oral delivery of BBR and test its therapeutic efficacy in a murine colitis model. The MNEHDS is formed by encapsulation of BBR-loaded poly(lactic-co-glycolic acid) nanoparticles into a pH-sensitive, BBR-pre-entrapped Eudragit FS30D matrix to form a hybrid microparticle composed of the BBR and BBR nanoparticles. Once in the colonic environment, the microencapsulated BBR is almost completely released for immediate action, while BBR nanoparticles can provide sustained release of BBR subsequent to their intestinal absorption. One dose of oral MNEHDS/BBR treatment results in significant attenuation of acute colitis induced by dextran sulfate sodium. The MNEHDS/BBR also proves to be effective during chronically induced colitis with two doses given 1 week apart. The improved efficacy is accompanied by decreased production of colon inflammation. Comparatively, oral treatment with one or two 7-day courses of free BBR has less effect on ameliorating either acute or chronic colitis. Thus, MNEHDS represents a novel delivery system for BBR, and potentially other therapeutic agents, to treat inflammatory bowel disease.

Achieving delayed release of freeze-dried probiotic strains by extrusion, spheronization and fluid bed coating - evaluated using a three-step in vitro model.

Intake of probiotics is associated with many health benefits, which has generated an interest in formulating viable probiotic supplements. The present study had two aims. The first aim was to achieve gastrointestinal protection and delayed release of viable probiotics by pelletizing and coating freeze-dried probiotic strains, using riboflavin as a marker for release. The second aim was to set up a dynamic three-step in vitro model simulating the conditions in the human gastric, duodenum/jejunum and ileum compartments using physiologically relevant media to evaluate delayed release of the formulations. To simulate lowered bile acid concentrations in the ileum area of the gastrointestinal tract, a novel method using the bile acid sequestrant cholestyramine to lower bile acid concentrations in the small intestinal medium to physiologically relevant levels was attempted. Granulation, extrusion and spheronization was used to develop pellets containing viable probiotics using freeze-dried Lactobacullus reuteri as a model strain. Fluid bed coating the pellets with the pH-sensitive polymers Eudragit S100 or Eudragit FS30D resulted in targeted release in the ileum step of the three-step in vitro model based on release of the marker riboflavin.

Colitis-targeted hybrid nanoparticles-in-microparticles system for the treatment of ulcerative colitis

Nanoparticle (NP)-based drug delivery systems accumulate in the disrupted epithelium of inflamed colon tissue in ulcerative colitis. However, premature early drug release and uptake or degradation of NPs during their passage through the harsh gastric or intestinal environment compromise their therapeutic outcomes. This study aimed to develop an advanced colitis-targeted hybrid nanoparticles-in-microparticles (NPsinMPs) drug delivery system to overcome the aforementioned challenges. First, sustained drug releasing poly(lactic-co-glycolic acid) NPs were generated and further encapsulated in pH-sensitive Eudragit FS30D MPs to ensure complete drug protection in a gastric-like pH and for selective delivery of NPs to the colon. SEM and confocal microscopy for the NPsinMPs revealed successful NP encapsulation. NPsinMPs prevented drug release in an acidic gastric-like and intestinal-like pH and presented a sustained release thereafter at an ileal and colonic pH, indicating the degradation of the outer pH-sensitive MPs and release of NPs. Furthermore, in vivo imaging of gastrointestinal tract of a colitis mouse orally administered with fluorescent NPsinMPs revealed higher fluorescence intensities selectively in the colon, demonstrating the release of loaded NPs and their concomitant accumulation at the site of colon inflammation. NPsinMPs markedly mitigated experimental colitis in mice indicated by improved histopathological analysis, decreased myeloperoxidase activity, neutrophils and macrophage infiltration, and expression of proinflammatory cytokines in colonic tissues compared with NP-treated mice. The present results show the successful formulation of an NPsinMP-based drug delivery system and provide a platform to improve NP-based colon-targeted drug delivery through improved protection of encapsulated NPs and their payload in the early small intestine.

Synthesis of Zinc Oxide Eudragit FS30D Nanohybrids: Structure, Characterization, and Their Application as an Intestinal Drug Delivery System.

The present study was designed to develop multifunctional zinc oxide-encapsulated Eudragit FS30D (ZnO/EFS) nanohybrid structures as a biodegradable drug delivery system and as a promising successful carrier for targeting sites. The solvent evaporation method was used to fabricate the ZnO/EFS nanohybrids and the size, shape, stability, and antioxidant activity were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), thermogravimetric analysis (TGA), and an antioxidant (1,1-diphenyl-2-picrylhydrazyl (DPPH)). Zinc oxide-encapsulated Eudragit FS30D (ZnO/EFS) nanohybrid structures consisted of irregularly shaped, 297.65 nm-sized ZnO/EFS microcapsule, enduring thermal stability from 251.17 to 385.67 °C. Nano-ZnO was encapsulated in EFS through the formation of hydrogen bonds, and the average encapsulation efficiency for nano-ZnO was determined to be 96.12%. In vitro intestinal-targeted drug release assay provided 91.86% with free nano-ZnO, only 9.5% in acidified ZnO/EFS nanohybrid structure but the rate ZnO/EFS nanohybrids reached 93.11% in succus entericus resultantly modified nano-ZnO was proven proficient intestinal-specific delivery system. The stability of the ZnO/EFS nanohybrid structures was confirmed using ζ-potential and antioxidant activity analysis. Hence, the EFS nanoencapsulation strategy of ZnO provided a stable, nontoxic, and pharmacokinetically active intestine-specific system that can become the best choice for an effective oral feed additive in future.

Design and Development of Pulsatile drug delivery of Diltiazem Hydrochloride

In the present study, an effort was made to develop a novel dosage form by using a chrono-pharmaceutical approach for the treatment of hypertension using Diltiazem hydrochloride as a model drug. A time delayed capsule was prepared by sealing the pellets inside the insoluble hard gelatin capsule body with erodible hydrogel plug. The pellets were prepared by emulsion Fluidized Bed Wurster (bottom spray) technology technique. Optimized pellets formulations were selected based on dissolution studies. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. Hydrogel plug (HPMCK4 and lactose in 1: 1 ratio) having 4.5kg/cm2 hardness and 100 mg weight was placed in the capsule opening and found that it was suitable to avoid the drug release in small intestinal fluid and to eject out the plug in colonic fluid and releasing the pellets into colonic fluid after a lag time criterion of 5 hours. In order to simulate the pH changes along the GI tract, three dissolution media with pH 1.2, 7.4 and 6.8 were successively used. FTIR study confirmed that there was no interaction between drug and polymer. Among all the formulations Diltiazem hydrochloride pellets coated with Eudragit FS 30D in 35% w/w concentrations shown prolonged release for a period of 12 hours. The obtained results revealed the capability of the system in delaying drug release for a programmable period of time and can prevent a sharp increase in the incidence of blood pressure, during the early morning hours, a time when the risk of hypertension attacks is the maximum.

Novel Eudragit® -based polymeric nanoparticles for sustained release of simvastatin

This paper reports on the development of nanoparticles aiming at the in vitro controlled release of simvastatin (SVT). The nanoparticles were prepared by the nanoprecipitation method with polymers Eudragit® FS30D (EDGFS) or Eudragit® NE30D (EDGNE). EDGFS+SVT nanoparticles showed mean size of 148.8 nm and entrapment efficiency of 76.4%, whereas EDGNE+SVT nanoparticles showed mean size of 105.0 nm and entrapment efficiency of 103.2%. Infrared absorption spectra demonstrated that SVT incorporated into the polymer matrix, especially EDGNE. Similarly, the differential scanning calorimeter (DSC) curve presented no endothermic peak of fusion, indicating that the system is amorphous and the drug is not in the crystalline state. The maintenance of SVT in the amorphous state may favors its solubilization in the target release sites. In the in vitro dissolution assay, the SVT incorporated into the EDGFS+SVT nanoparticles showed a rapid initial release, which may be related to the pH of the dissolution medium used. Regarding the EDGNE+SVT nanoparticles, the in vitro release occurred in a bimodal behavior, i.e., an initial “burst” followed by a sustained delivery, with the kinetics of drug release following Baker-Lonsdale’s mathematical model. All these features suggest the nanoparticulate system’s potential to modulate SVT delivery and enhance its bioavailability.

FORMULATION DEVELOPMENT OF COLON TARGETED MESALAMINE PELLETS: IN VITRO-IN VIVO RELEASE STUDY

Objective: This study was intended to investigate the potential of the colon specificity approach comprising of use of pH-sensitive and time-dependent polymers in combination for precise colonic release of Mesalamine or 5-Aminosalicylic acid (5-ASA).
 Methods: The extrusion and spheronization method, preferably employed in industry for allowing high dose capacity to formulate, was used to prepare drug pellets. The Wurster coating technique used for aqueous coatings of Eudragit NE 40D as an inner coat and Eudragit FS30D as outer coat. The changing pH media used for in vitro release study of optimization batches for both the coating levels. A scanning electron microscope (SEM) was used to evaluate coating thickness and surface morphology.
 Results: The pharmacokinetic parameters of formulation evaluated by in vivo study in rabbits revealed that the uncoated formulation released the drug too early in the gastrointestinal tract (GIT) with a mean Cmax of 1205.28±0.37 µg/ml at 2 h after administration, whereas desired lag time was achieved in case of coated pellets exhibiting mean Cmax 465.94±0.21 µg/ml and tmax of 8 h.
 Conclusion: The in vitro and in vivo release study divulge the reliability of approach involving the use of pH sensitivity and time dependency of polymer for drug release in a single formulation for the treatment of colonic diseases. Hence, the present study provides constructive results for colon targeting of 5-ASA pellets with industrially feasible processes.

In vitro -In vivo- In silico Simulation of Experimental Design Based Optimized Curcumin Loaded Multiparticulates System.

The present study focused to optimize dual coated multiparticulates using Box-Behnken Experimental Design and in-silico simulation using GastroPlusTM software. The optimized formulations (OB1 and OB2) were comparatively evaluated for particle size, morphological, in vitro drug release, and in vivo permeation studies. In silico simulation study predicted the in vivo performance of the optimized formulation based on in-vitro data. Results suggested that optimized formulation was obtained using maximum content of Eudragit FS30D and minimum drying time (2 min). In vitro data corroborated that curcumin release was completely protected from premature drug release in the proximal part of gastro intestinal tract and successfully released to the colon (95%) which was closely predicted (90.1 %) by GastroPlusTM simulation technique. Finally, confocal laser scanning microscopy confirmed the in-vitro findings wherein maximum intensity was observed with OB1 treated group suggesting successful delivery of OB1 to the colon for enhanced absorption as predicted in regional absorption profile in ascending colon (30.9%) and caecum (23.2%). Limited drug absorption was predicted in small intestine (1.5-8.7%). The successful outcomes of the research work minimized the release of curcumin in the upper gastric tract and the maximized drug access to the colon (pH 7.4) as prime concern.

FORMULATION DEVELOPMENT AND PHARMACODYNAMIC EVALUATION OF COLON TARGETED CONTROLLED RELEASE LORNOXICAM PELLETS FOR PAIN MANAGEMENT OF RHEUMATOID ARTHRITIS

The aim of the present research work was to formulate and evaluate colon targeted pellets of lornoxicam for the pain management of rheumatoid arthritis. The product and process parameters were optimized by screening methods. Pellets were prepared by extrusion spheronization method using microcrystalline cellulose (MCC) as spheronizing aid and ethyl cellulose (EC) as controlled release polymer, in different ratios. Based on the physical appearance, sphericity and % in vitro drug release, batch B17 containing EC: MCC (6:4) was optimized for core pellets. The site specificity was obtained by screening Eudragit FS30D and Eudragit S100 as coating polymers and the core pellets were coated with Eudragit S100. The batch C4 (6%) showed appropriate physical appearance and % in vitro drug release upto 24 h, indicating controlled release property. The pharmacodynamic studies performed on rat model indicated the anti-inflammatory activity of pellet formulation. Thus, it is concluded that the coated pellets can be a good candidate for site specific delivery of lornoxicam to colon by decreasing the gastric irritation, reducing dose frequency and improving patient compliance.

Design, development, optimization and Invitro evaluation of core-in-cup tablet coated with Eudragit FS30D for modulated release of Mefenamic acid in colon.

Design, development, optimization and Invitro evaluation of core-in-cup tablet coated with Eudragit FS30D for modulated release of Mefenamic acid in colon.

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis.

BackgroundColon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer.MethodsCSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs.ResultsPNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum–colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs.ConclusionOverall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

Biodistribution and targeting potential assessment of mucoadhesive chitosan nanoparticles designed for ulcerative colitis via scintigraphy.

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. Methods: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS–CN-NPs were coated with Eudragit FS 30D by using a solvent evaporation method. Different process parameters were evaluated, and the optimized formulation was characterized by particle size, size distribution, zeta potential and encapsulation efficiency before lyophilization. The lyophilized product was further subjected to Fourier-transform infrared spectroscopy, and particle morphology and in vitro drug release in different media were studied. Results: the kinetics of in vitro drug release from the CS–CN-NPs revealed sustained release behaviour of the developed carriers. In vivo biodistribution study by gamma-scintigraphy showed good accumulation of the developed nanocarriers in the colonic region. Conclusion: sustained and pH stimulated delivery of CN to the colon was successfully attained via coating of CS-NPs with Eudragit FS 30D to circumvent poor absorption and availability of CN.

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank’s solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank’s solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

In vivo evaluation of pH and time-dependent polymers as coating agent for colonic delivery using central composite design

The objective of this study was to evaluate the combination of pH-dependent and time-dependent polymers on drug release in order to optimize coating for colonic delivery. Response surface methodology (RSM) based on central composite design (CCD) was employed for formulation optimization. Theophylline was used as model drug and Eudragit® FS 30D and hydroxypropyl methylcellulose (HPMC) were used as pH-dependent and time-dependent polymer, respectively. Dissolution test was carried out using the release conditions as follow: pH 1.2 for 2 h, pH 6.8 for 2 h, pH 7.4 for 3 h and pH 6.8 for 3 h. Scanning electron microscopy (SEM) was applied to observe the morphology of coated capsules. Drug release was evaluated spectrophotometrically. In vivo X-ray imaging study was used to trace the movement and behavior of the capsules in gastrointestinal (GI) tract. The optimized formulation containing 0.5% HPMC and 80% Eudragit FS 30D was prepared according to the software determined levels. There was no drug release for 2 h at pH 1.2 and for 2 h at pH 6.8. Optimum values of drug release were 32.57% and 71.37% at pH 7.4 (7 h) and pH 6.8 (10 h), respectively, which were in agreement with the predicted value by RSM. Surface coated capsules were rougher than gelatin capsules as examined by SEM. X-ray analysis confirmed that coated capsules dissolved at the targeted colon region. The results of this study indicate that the designed system can be potentially used as a carrier for colon delivery of drugs.

Mesalamine-loaded alginate microspheres filled in enteric coated HPMC capsules for local treatment of ulcerative colitis: in vitro and in vivo characterization

An attempt was made to formulate mesalamine-loaded alginate microspheres by emulsion cross linking method for local treatment of ulcerative colitis. Microspheres were filled in HPMC capsules enteric coated with Eudragit FS-30D. The effect of process variables like drug-alginate concentration ratio and emulsifier concentration was optimized. Microspheres were evaluated for particle size, shape and entrapment efficiency. Spherical shaped microspheres were confirmed by scanning electron microscopy. In vitro drug release study showed a burst drug release pattern in the initial hour necessitating encapsulation of alginate microspheres. In vivo study in rats performed by colonic inflammatory lesions demonstrated remarkable reduction in ulcer index treated with microspheres. Histopathological study confirmed no signs of ulceration or bleeding. Microspheres (drug:alginate concentration, 1:1) was then filled in HPMC capsule shells, enteric coated with Eudragit FS 30D to gain 30 mg weight. Due to solubility of Eudragit FS30D above pH 7, an encapsulated system released alginate microspheres at colon region. Capsules with weight gain of 30 mg coating polymer (B3) resisted the drug release at intestinal region for about 6 h with 10% drug release. In vitro drug release of formulation B3 showed 64.89 and 90.52% drug release within 10 h, in phosphate buffer pH 7.4 and in presence of rat faecal content in simulated colonic fluid, respectively. The later rapid drug release was due to action of colonic microflora at alginate microspheres. Therefore, mesalamine-loaded alginate microspheres enteric coated in HPMC capsules can be potential delivery system for local treatment of ulcerative colitis.