Prevent Drug Release Research Articles

Design and Characterization of Dual Drug Loaded Microspheres for Colon Drug Targeting

The present investigation was focus to prepared and characterized eudragit coated pectin microspheres for the delivery of mesalamine and prednisolone to the colon. The pectin microspheres were prepared using emulsion dehydration technique. A 33 full factorial design (three variables in three levels) was employed to evaluate the combined effect of the selected independent variables: drugs to polymer ratio, emulsifier concentrations and stirring speed on dependent variables such as particle size and size distribution, percentage yield, % drug entrapment and swelling ratio. Optimized formulation i.e. F18, F24, and F27 were coated with eudragit S100 by the solvent evaporation technique to prevent drug release in the stomach. Eudragit S100 coated pectin microspheres were further characterized for coating thickness and in-vitro release kinetics. The cumulative percent drug release of mesalamine and prednisolone from formulation in pH 7.4 phosphate buffer was found to be 97.01 + 1.35% and 96.89 + 0.67% for mesalamine and prednisolone, respectively. Optimized formulation (F24) was characterized for in-vivo studies. The eudragit-coated pectin microspheres may improve therapeutic efficacy by local action and reduce the side effects by minimizing the systemic absorption of mesalamine and prednisolone. Amalgamation of mesalamine and prednisolone in therapeutic regimen will show synergism action for treatment of UC.

In Vitro Dissolution Model Can Predict the in Vivo Taste Masking Performance of Coated Multiparticulates.

The majority of active pharmaceutical ingredients (APIs) are bitter. Therefore, compliance can be a problem where adequate taste masking has not been achieved; this is most problematic in pediatrics. Taste masking is thus a key stage during pharmaceutical development with an array of strategies available to the formulation scientist. Solid oral dosage forms can be taste-masked quite simply by polymer coating, which prevents drug release in the mouth, without unwantedly impairing drug release further down the gastrointestinal tract. At the early stages of pharmaceutical development, an in vitro method for the assessment of taste masking is necessary given the lack of toxicological data preventing the use of human taste panels. Currently, there is no such tool allowing prediction of taste masking efficiency. In this study, drug dissolution in the context of aversive taste thresholds was proposed as a means to bridge this knowledge gap. Thus, a biorelevant buccal dissolution test was developed in which previously determined taste thresholds in vivo were used to evaluate taste masking efficiency: if drug release exceeded said thresholds, the formulation was deemed to be poorly taste-masked, and vice versa. This novel dissolution test was compared to the USP I (basket) dissolution test, and the biopharmaceutical implications of taste masking were also assessed by performing USP I (basket) dissolution testing in simulated gastric fluid (SGF). Chlorphenamine maleate, a model bitter BCS class 1 API, was layered onto sugar spheres and taste-masked using polymer coatings. An array of coating technologies were employed and assessed single blinded: two pH-independent water-insoluble coatings (Surelease:Opadry at 8, 12, and 16% weight gain and Opadry EC at 4, 6, and 8% weight gain) and a pH-dependent water-insoluble reverse-enteric coating (developmental fully formulated system based on Kollicoat Smartseal 100P at 10% weight gain). Both the biorelevant buccal and the USP I dissolution tests were capable of discriminating between both type and level of coating used. However, only the buccal dissolution test was able to provide absolute quantification of the level of taste masking achieved in the context of previously determined taste thresholds, while the USP I test merely provided a relative comparison between the different technologies assessed. When the release data from the buccal test were assessed in parallel to that in SGF, it was possible to predict in vitro optimized taste masking without compromising bioavailability. The fully formulated system based on Smartseal 100P was identified as the most effective coating and Surelease:Opadry the least effective. The developed methodology provides true insight for the formulator, enabling more informed patient-centric formulation decisions, better taste masking, and ultimately more effective medicines.

Synthesis, in-vitro characterization and pharmacological evaluation of conjugates of flurbiprofen and polysaccharides for colon specific drug delivery

The aim of the study was to prepare site specific drug delivery of flurbiprofen using polysaccharides by the formation of glycosidic linkage which is hydrolysed by the microflora present in colon. This approach prevents drug release in the upper gastrointestinal environment. Due to the minimal degradation of conjugates in upper Git, the in vitro drug release in SGF, SIF and SCF was found upto 4.26±0.03%, 12.41±0.08% and 92.72±3.33% respectively.
 Keywords: Colon specific drug delivery, Conjugates, Flurbiprofen, Microbial system.

Determination of Eudragit® L100 in an Enteric-Coated Tablet Formulation Using Size-Exclusion Chromatography with Charged-Aerosol Detection.

Eudragit® L100 is a commonly used polymer in a coating layer of modified-release drug formulation to prevent drug release in the stomach. The amount of Eudragit® L100 in the formula determines the dissolution profile of drug at its release medium. Hence, its quantification in reference product will facilitate the formulation of a bioequivalent drug product. Some analytical methods including size-exclusion chromatography (SEC) have been reported for characterization of Eudragit® L100 either as single component or its conjugate with the enzyme, but none for its quantification in drug formulation. In this work, an SEC method with charged-aerosol detection (CAD) was developed for determination of Eudragit® L100 in an enteric-coated tablet formulation using Waters Ultrahydrogel 1000 and Waters Ultrahydrogel 120 columns in series. The mobile phase was a mixture of 90:10 (v/v) 44.75 mM aqueous ammonium acetate buffer, pH 6.6 and acetonitrile pumped at a constant flow rate of 0.8 mL/min in isocratic mode. The method was validated for specificity, working range, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision. The method was shown to be specific for Eudragit® L100 against the diluent (mobile phase) and placebo of a coating layer for the tablet. A good correlation coefficient (r = 0.9997) of CAD response against Eudragit® L100 concentration from 0.1⁻1.0 mg/mL was obtained using polynomial regression. LOD and LOQ concentrations were 0.0015 and 0.0040 mg/mL, respectively. The mean recovery of Eudragit® L100 was in the range of 88.0⁻91.1% at three levels of working concentration: 50%, 100% and 150%. Six replicated preparations of samples showed good precision of the peak area with % relative standard deviation (RSD) 2.7. In conclusion, the method was suitable for quantification of Eudragit® L100 in an enteric-coated tablet formulation.

The effect of food and liquid pH on the integrity of enteric-coated beads from cysteamine bitartrate delayed-release capsules.

BackgroundCysteamine bitartrate delayed-release (DR) capsule (Procysbi®) is approved for treatment of nephropathic cystinosis in the USA, Canada, and the EU. The capsules contain cysteamine bitartrate beads that are enteric coated with acid-resistant Eudragit L 30 D-55, preventing drug release in the acidic stomach environment while allowing dissolution of the beads in the more alkaline environment of the small intestine. Patients who have difficulty swallowing capsules can open capsules, sprinkle beads onto 4 ounces of a suitable food or liquid, gently mix, and consume the entire content within 30 minutes. Foods found to be suitable for administration, and described in the Procysbi US labeling, include fruit juices (except grapefruit juice), applesauce, and berry jelly; there are minor variations in the foods and liquids recommended by regulatory authorities in other countries. This study aimed to assess the stability of enteric-coated beads exposed to additional foods at different conditions to expand the list of suitable foods for drug administration.MethodsFor each test condition, beads from eight opened 75 mg cysteamine bitartrate DR capsules were gently mixed with test food and maintained at a prespecified temperature and duration; remaining undissolved beads were then recovered from the food. The recovered beads were split into two portions: one assayed for remaining drug content and the other subjected to dissolution testing to assess the effect on the drug-release profile.ResultsThe results show that bead integrity was maintained when mixed with foods at pH values <5.5 at all time points when refrigerated (2°C–8°C) and at room (20°C–22°C) and lukewarm (37°C–41°C) temperatures. Bead integrity was not maintained when mixed with foods at pH values of ≥5.5 at room temperature.ConclusionThe results from this in vitro dissolution study help in identifying additional foods that may be used for the administration of cysteamine bitartrate DR beads from opened capsules using the sprinkle method.

The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers.

The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it is shown that making drug-loaded Eudragit polymers effectively prevents drug release in low-pH media where the polymer is insoluble, this is not always the case, and other studies have reported significant amounts of drug release at acidic pHs. In this study, we sought to gain insight into the factors influencing the release of active ingredients from Eudragit S100 (ES100) fibers. A family of materials was prepared loaded with the model active ingredients (AIs) benzoic acid, 1-naphthoic acid, 1-naphthylamine, and 9-anthracene carboxylic acid. Analogous systems were prepared with an AI-loaded core and an ES100 sheath. The resultant fibers were smooth and cylindrical in the majority of cases, and X-ray diffraction and differential scanning calorimetry showed them to comprise amorphous solid dispersions. When AI release from the monolithic fibers was probed, it was found that there was significant release at pH 1 in all cases except with 9-anthracene carboxylic acid. Analysis of the results indicated that both the molecular weight of the AI and its acidity/basicity are important in controlling release, with lower molecular weight AIs and basic species released more quickly. The same release trends are seen with the core/shell fibers, but AI release at pH 1 is attenuated. The most significant change between the monolithic and core/shell systems was observed in the case of 1-naphthylamine. Mathematical equations were devised to connect molecular properties and AI release under acidic conditions.

Bacteria-Targeting Nanoparticles with Microenvironment-Responsive Antibiotic Release To Eliminate Intracellular Staphylococcus aureus and Associated Infection.

Staphylococcus aureus ( S. aureus) is a causative agent in life-threatening human diseases that afflict millions of people annually. Traditional antibiotic treatments are becoming less efficient because S. aureus can invade host cells including osteoblasts and macrophages, constituting a reservoir that is relatively protected from antibiotics that can lead to recrudescent infection. We herein report a unique intracellular antibiotic delivery nanoparticle, which is composed of (i) a mesoporous silica nanoparticle (MSN) core loaded with gentamicin, (ii) an infected microenvironment (bacterial toxin)-responsive lipid bilayer surface shell, and (iii) bacteria-targeting peptide ubiquicidin (UBI29-41) that is immobilized on the lipid bilayer surface shell. The lipid material acts as a gate that prevents drug release before the MSNs reach the target cells or tissue, at which point they are degraded by bacterial toxins to rapidly release the drug, thus eliminating efficient bacteria. We confirm rapid drug release in the presence of bacteria in an extracellular model and observe that S. aureus growth is effectively inhibited both in vitro and in vivo of planktonic and intracellular infection. The inflammation-related gene expression in infected preosteoblast or macrophage is also downregulated significantly after treatment by the antibiotic delivery nanoparticles. The antibiotic delivery nanoparticles offer advantages in fighting intracellular pathogens and eliminating the inflammation caused by intracellular bacterial infections.

Studies on the Development and Evaluation of Colon Targeted Mesalamine Tablets based on Eudragit L100-Chitosan Interpolyelectrolye Complexes

An attempt was made to prepare and evaluate colon targeted Mesalamine tablets based on interpolyelectrolyte complex. Tablets were prepared by wet granulation technique using varying ratios of Eudragit L100 (EL) and Chitosan (CS) polymers. Results obtained showed that the tablets conformed to compendial requirements for acceptance and CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of Mesalamine from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (-CO-) group of EL and amino (-NH3 +) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released Mesalamine in a zero-order manner.

FORMULATION, OPTIMIZATION, CHARACTERIZATION AND IN VIVO ANTI-ULCER ACTIVITY OF ESOMEPRAZOLE MAGNESIUM TRIHYDRATE GASTRORESISTANT MICROSPHERES

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of the present investigation was to prepare gastro-resistant microspheres of esomeprazole magnesium trihydrate (EMT) to prevent its degradation in the acidic environment of the stomach and enhance its bioavailability via intestinal absorption.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EMT loaded gastro-resistant microspheres were prepared using hypromellose acetate succinate (HPMCAS) as the gastro-resistant polymer by ‘non-aqueous solvent evaporation’ technique. A 3-factor 3 level factorial design was used to optimise EMT: HPMCAS ratio, the concentration of Span 80 and stirring speed with respect to percent entrapment efficiency and particle size. Further characterization was carried out using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), &lt;em&gt;In vitro&lt;/em&gt; release study and &lt;em&gt;In vivo&lt;/em&gt; anti-ulcer activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fourier transform infrared &lt;strong&gt;(&lt;/strong&gt;FTIR) study indicated compatibility between drug and polymer. DSC study revealed that the drug was molecularly dispersed in the polymer. The optimised batch showed 49.63±1.23% drug entrapment and 170.12±3.36 μm particle size. SEM study showed that microspheres were spherical in shape&lt;strong&gt;. &lt;/strong&gt;&lt;em&gt;In vitro&lt;/em&gt; drug release study showed only 4.28±1.23% drug release in simulated gastric media in 2 hr and 93.46±1.20% release in simulated intestinal media after 1 hr from the optimised batch.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Results of &lt;em&gt;in vitro &lt;/em&gt;release studies indicated the gastro-resistant nature of the developed microspheres. &lt;em&gt;In vivo&lt;/em&gt; anti-ulcer activity demonstrated that EMT loaded microspheres were able to significantly reduce ethanol-induced ulcer formation in rats’ stomach as compared to the aqueous solution of EMT. So it can be concluded that the developed gastro-resistant microspheres of EMT prevented drug release in the stomach which would lead to a significant improvement in its bioavailability through enhanced intestinal absorption&lt;/p&gt;

Development and characterization of crosslinked hyaluronic acid polymeric films for use in coating processes

The aim of this work was to develop and characterize new hyaluronic acid-based responsive materials for film coating of solid dosage forms. Crosslinking of hyaluronic acid with trisodium trimetaphosphate was performed under controlled alkaline aqueous environment. The films were produced through casting process by mixing crosslinked or bare biopolymer in aqueous dispersion of ethylcellulose, at different proportions. Films were further characterized regarding morphology by scanning electron microscopy, robustness by permeation to water vapor transmission, and ability to hydrate in simulated gastric and intestinal physiological fluids. The safety and biocompatibility of films were assessed against Caco-2 and HT29-MTX intestinal cells. The permeation to water vapor transmission was favored by increasing hyaluronic acid content in the final formulation. When in simulated gastric fluid, films exhibited lower hydration ability compared to more extensive hydration in simulated intestinal fluids. Simultaneously, in simulated intestinal fluids, films partially lost weight, revealing ability for preventing drug release at gastric pH, but tailoring the release at higher intestinal pH. The physiochemical characterization suggests thermal stability of films and physical interaction between compounds of formulation. Lastly, cytotoxicity tests demonstrated that films and individual components of the formulations, when incubated for 4h, were safe for intestinal cells Overall, these evidences suggest that hyaluronic acid-based responsive films, applied as coating material of oral solid dosage forms, can prevent the premature release of drugs in harsh stomach conditions, but control the release it in gastrointestinal tract distal portion, assuring safety to intestinal mucosa.

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.

Preparation of Colon-specific and Synchronous Release Pellet Containing Total Alkaloids of Sophora alopecuroides

ObjectiveTo deliver multiple component drugs to colon site and sustain a synchronous release for better therapeutic effect. For achieving this purpose, colon specific pellet containing total alkaloids of Sophora alopecuroides (TASA) was prepared. MethodsThe pellet was prepared by extrasion-spheronizing and subsequently coated with three layers of two polymers. ResultsThe pellet core consisted of 40% TASA, 1:2 in ratio of Bletilla striata polysaccharide (BSP), an enzyme-degradable material, to microcrystalline cellulose (MCC), filler, and 1% CMC-Na solution as binder by optimization. Concerning of the three coated layers, the outer layer was coated with Eudragit RS30D for controlling drug release in colon, the intermediate layer and the inner layer were coated with same polymer, Eudragit S100, for preventing drug release in upper gastrointestinal tract, which required 23.2%, 21.7%, and 9.3% weigh gain, respectively. The coated pellets released 1.20% of sophoridine and 1.98% of matrine in media mimicking the stomach condition for 2 h, and 23.88% of sophoridine and 22.91% of matrine in media mimicking the intestine for 3 h and finally 90.25% of sophoridine and 89.94% of matrine in colonic conditions within 24 h. And the similarity factor f of sophoridine and matrine of release curve for investigated formulation was internal in (50–100) and > 80, demonstrating that sophoridine and matrine in formulation achieved a synchronous release. ConclusionThe coated pellets achieve a certain colon-specific release and synchronous release.

Evaluation of Ibuprofen Colon Delivery System using Grewia mollis Juss. (Tiliaceae) stem bark gum as Matrix-former

Aim: The aim of this research was to evaluate Grewia gum as a matrix-former for colon delivery of ibuprofen. Methodology: The gum was extracted by soaking the dried stem bark powder in aqueous solution of sodium metabisulphite for 48 h. Ibuprofen granules were prepared by wet granulation method using Grewia gum at 10, 20, 30, 40 and 50% w/w. The tablets were compressed using 12 mm punch. The physicochemical parameters-uniformity of weight, thickness, diameter, crushing strength, friability, disintegration time were evaluated. The in vitro drug release studies were conducted in simulated gastric fluid at 37 ± 1° and 100 rpm. The kinetics and mechanism of drug release were determined. The tablets were compared with those of hydroxypropylmethyl cellulose (HPMC) (80-120 cp; H9262) at the same concentrations. Results: The results revealed that Grewia gum is highly viscous, not readily soluble in water and has a high swelling capacity (237.5% w/w). It also has moderate flow profile, and large particle size. The matrix tablets containing 40 and 50 % w/w of Grewia gum exhibited highest swelling capacity and showed better ability to offer barrier to drug release in the upper GIT and delivery to colon. None of the matrix containing HPMC was able to prevent drug release in the upper GIT. The in vitro drug release in the absence and presence of rat cecal contents showed no significant difference (p<0.05) using ANOVA. The release kinetics followed zero-order and the mechanism of release was Korsmeyer-peppas super case II mechanism. Conclusion: The findings show that Grewia gum may be used as an effective matrix-former for the delivery of ibuprofen to colon.

5-Fluorouracil loaded Eudragit fibers prepared by electrospinning

A series of 5-fluorouracil (5-FU) loaded core/shell electrospun fibers is reported. The fibers have shells made of Eudragit S100 (ES-100), and drug-loaded cores comprising poly(vinylpyrrolidone), ethyl cellulose, ES-100, or drug alone. Monolithic 5-FU loaded ES-100 fibers were also prepared for comparison. Electron microscopy showed all the fibers to have smooth cylindrical shapes, and clear core–shell structures were visible for all samples except the monolithic fibers. 5-FU was present in the amorphous physical form in all the materials prepared. Dissolution studies showed that the ES-100 shell was not able to prevent drug release at pH 1.0, even though the polymer is completely insoluble at this pH: around 30–80% of the maximum drug release was reached after 2h immersion at pH 1.0. These observations are ascribed to the low molecular weight of 5-FU permitting it to diffuse through pores in the ES-100 coating, and the relatively high acid solubility of the drug providing a thermodynamic impetus for this to happen. In addition, the fibers were observed to be broken or merged following 2h at pH 1.0, giving additional escape routes for the 5-FU.

Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement.

Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions. They can be applied by minimally invasive surgery and can also be used as drug delivery systems. Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest. However, previous studies have commonly evaluated the drug release using pre-set cements only. Therefore, the aim of this work was to determine if the time elapsed from cement preparation until immersion in the solution (3 min for fresh cements, and 1h and 15 h for pre-set cements) had an influence on its physical properties, and correlating these to the drug release profile. Simvastatin was selected as a model drug, while brushite cement was used as drug carrier. This study quantified how the setting of a material reduces the accessibility of the release media to the material, thus preventing drug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements to a sustained release for pre-set cements.

PH-triggered drug release from biodegradable microwells for oral drug delivery.

Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240μm and a height of 100μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastro-resistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH1.6) was employed, after which a change to biorelevant intestinal release medium (pH6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.

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

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

Colonic Drug Delivery Systems Based on Natural Polysaccharides and their Evaluation

Natural polysaccharides are found in abundance, are inexpensive, safe and available in a variety of structures which can easily be modified chemically and biochemically. A number of natural gums and mucilages along with their chemically modified forms have been evaluated as controlled drug delivery devices. They are reported to be capable of providing the desired drug release profiles and in some cases, have shown comparable drug release properties with currently available sustained release products in the market. Colon specific drug delivery based on natural polysaccharides has highly been acclaimed in recent years. A colon specific drug delivery system should prevent drug release in the stomach as well as the small intestine. Several polysaccharides have been reported to be capable of preventing drug release in the upper GI tract while being susceptible to enzymatic degradation by colonic bacterial enzymes. A wide range of natural or modified polysaccharides has been investigated for peroral delivery of drugs to the colon. As the release of drug from these polysaccharides based systems is independent of pH and gastric emptying time these polysaccharides based systems are considered the most effective and preferable means for colonic drug delivery in terms of target specificity.

Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes

Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (–CO–) group of EL and amino (–NH3 +) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs.

Colon specific drug delivery of mesalamine using eudragit S100-coated chitosan microspheres for the treatment of ulcerative colitis

The purpose of the present study was to prepare, characterize and evaluate the colon-targeted microspheres of mesalamine for the treatment and management of ulcerative colitis (UC). Microspheres were prepared by the ionic-gelation emulsification method using tripolyphosphate (TPP) as cross linking agent. The microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach. The prepared microspheres were evaluated for surface morphology, entrapment efficiency, drug loading, micromeritic properties and in-vitro drug release. The microspheres formed had rough surface as observed in scanning electron microscopy. The entrapment efficiency of microspheres ranged from 43.72%-82.27%, drug loading from 20.28%-33.26%. The size of the prepared microspheres ranged between 61.22-90.41µm which was found to increase with increase in polymer concentration. All values are statistically significant as p&lt;0.05. Micromeritic properties showed good flow properties and packability of prepared microspheres. The drug release of mesalamine from microspheres was found to decrease as the polymer concentration increases. The release profile of mesalamine from eudragit-coated chitosan microspheres was found to be pH dependent. It was observed that Eudragit S100 coated chitosan microspheres gave no release in the simulated gastric fluid, negligible release in the simulated intestinal fluid and maximum release in the colonic environment. It was concluded from the study that Eudragit-coated chitosan microspheres were promising carriers for colon-targeted delivery of Mesalamine.DOI: http://dx.doi.org/10.3329/icpj.v2i3.13577 International Current Pharmaceutical Journal, February 2013, 2(3): 42-48