Development of Polysaccharide-Based Colon Targeted Drug Delivery Systems for the Treatment of Amoebiasis

ABSTRACT

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30–40% drug release during the initial 4–5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18–24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Influence of natural polymer coating on novel colon targeting drug delivery system

A novel colon targeted tablet formulation was developed using natural polysaccharides such as chitosan and guar gum as carriers and diltiazem hydrochloride as model drug. The prepared blend of polymer-drug tablets were coated with two layers, inulin as an inner coat followed by shellac as outer coat and were evaluated for properties such as average weight, hardness and coat thickness. In vitro release studies of prepared tablets were carried out for 2 h in pH 1.2 HCl buffer, 3 h in pH 7.4 phosphate buffer and 6 h in simulated colonic fluid (SCF) in order to mimic the conditions from mouth to colon. It was observed that 4% w/v of rat cecal contents in saline phosphate buffer (SCF) incubated for 24 h provides suitable conditions for in vitro evaluation of the formulations prepared. The drug release from the coated system was monitored using UV/ Visible spectroscopy. In vitro studies revealed that the tablets coated with inulin and shellac have controlled the drug release in stomach and small intestinal environment and released maximum amount of drug in the colonic environment. Among the polymers used, chitosan was found to be the suitable polymer for colon targeting. The study revealed that polysaccharides as carriers and inulin and shellac as coating materials can be used effectively for colon targeting of drugs for treating local as well as systemic disorders.     

Eudragit S100 coated microsponges for Colon targeting of prednisolone

Context: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease.

Objective: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery.

Materials and methods: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72?kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release.

Results: PLMs were found to be nano-porous spherical microstructures with size around 35?µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1?hr in SGF (pH 1.2), 2 to 3?h in SIF (pH 4.6), 4–5?h in SIF (pH 6.8), and 6–24?h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24?h.

Discussion and conclusion: In vitro drug release studies revealed that drug starts releasing after 5?h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.     

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Sustained-release from Layered Matrix System Comprising Chitosan and Xanthan Gum

ABSTRACT

Sustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH₃⁺ of chitosan molecule and COO^? of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.     

Film Coated Pellets Containing Verapamil Hydrochloride: Enhanced Dissolution into Neutral Medium

Abstract

Weakly basic drugs, such as verapamil hydrochloride, that are poorly soluble in neutral/alkaline medium may have poor oral bioavailability due to reduced solubility in the small intestine and colon. Film coated pellets were prepared using two strategies to enhance drug release at high pH values. Firstly, pellets were coated with Eudragit® RS/hydroxypropyl methylcellulose acetate succinate (HMAS) mixtures in proportions of 10:1 and 10:3, respectively. The enteric polymer, HMAS, would dissolve in medium at pH>6 creating pores through the insoluble Eudragit RS membrane to increase drug release. Secondly, an acidic environment was created within the core by the inclusion of fumaric acid at concentrations of 5 and 10% in order to increase drug solubility. Both strategies enhanced drug release into neutral medium in dissolution studies using the pH change method to simulate GIT transit. Dissolution profiles of samples tested in pH 1.2 for 12 hr were compared with those using the pH change method (pH 1.2 for first 1.5 hr, pH raised to 6.8 for remaining 10.5 hr) using the area under the dissolution curve (AUC), the dissolution half-life (t_50%), and the amount of drug released in 3 hr (A_{3 hr}) values. Both strategies enhanced drug release into neutral medium although the strategy using HMAS in the film was more effective. The formulation least affected by pH change was a combination of the two strategies, i.e., pellets containing 5% fumaric acid coated with Eudragit RS 12% w/w and HMAS 1.2% w/w.     

Elaboration and "in vitro" characterization of 5-ASA beads

The purpose of this research was to perform the design and in vitro evaluation of alginate beads containing 5-ASA in order to achieve an oral system that protects the drug until it reaches the colon. Alginate beads were prepared by the well-known ionic gelation reaction (Ca2+). The influence of the incorporation of several polymers (Eudragit FS 30D, Eudragit S100, and chitosan) in the initial formulation was studied. In all formulations, entrapment efficiencies of the drug higher than 70% were obtained. The scanning electron microscopy (SEM) study of beads showed homogeneous sizes and shapes in all cases. Finally, the release behavior of these polymeric beads were also studied and compared. The results indicated that Eudragit FS 30D (26%) showed the most favorable dissolution behavior in terms of achieving a controlled release of 5-ASA. To determine the mechanism of drug release from these beads, the Korsmeyer equation was applied. Qt/Qinfinity <0.9 can be described using a Higuchi model and Qt/Qinfinity=0.7 showed a zero-order release period. This formulation was assayed at other different pH values (pH=6; 6.8; 7.2) to assure that there is no release of 5-ASA until the system reaches the colon. No release was observed at pH 6.0. Release was very slow at pH 6.8; averages about 20% an hour at pH 7.2 and was complete within 4 hour at pH 7.4. So, these Eudragit FS beads exhibited interesting dissolution profiles for the therapy of colon pathologies.     

Modulated release of 5-fluorouracil from pH-sensitive and colon targeted pellets: An industrially feasible approach

Pellets, reliant on pH-sensitivity and time-dependency for drug delivery, provide one of the most versatile opportunities for targeting colon. 5-Fluorouracil (5-FU) loaded pellets were prepared by extrusion-spheronization using Avicel^® PH101 as a spheronization aid and hydroxypropylmethylcellulose K4M (HPMC K4M) solution as a binder. A 3² full factorial design was employed to optimize spheronization speed and time. Obtained pellets were evaluated for flow properties, pellet size, roundness and aspect ratio. Optimized batch was coated in a bottom-spray fluidized bed processor (FBP) with an inner coat of sustained release polymer Eudragit NE30D and an outer coat of pH-sensitive polymer Eudragit FS30D. The coating levels were statistically optimized and in vitro drug release was monitored by changing pH media method. Optimized system with 15% inner and outer coating levels revealed t_50% (time required for 50% drug release) to be about 9?h while almost complete drug was released in 24?h (98.71?±?1.33%) with highest dissolution efficiency (DE_24h) of 58.71%. The optimization model was validated; the predicted and experimental/actual values for validation batch (M1) were in close tolerance and the standard error (SE) was also small. Drug release was also studied at pH 7.4. Scanning electron microscopy (SEM) demonstrated average coating thickness to be 32.50?±?3.0 µm. Hence, the present study provides constructive results for colon targeting of 5-FU pellets with industrially feasible processes.     

Hydro-alcoholic media effects on theophylline release from sesamum polysaccharide gum matrices

Concomitant ingestion of alcohol and medications can greatly affect drug plasma concentrations as dose dumping or failure may occur as a result of the fact that formulation excipients may not always be resistant to alcohol. In this study, a natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized and used to formulate sustained release theophylline compacts to study the effect of varying alcohol concentrations (v/v) in dissolution media on drug release from these compacts. X-ray powder diffraction showed that the extracted gum was amorphous in nature with the powder having excellent compaction properties as observed with its compact being significantly harder than those prepared with pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that the compacts produced were homogenous in nature, however, swelling studies showed failure of the compacts at the highest concentration of absolute ethanol used (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested (f₂?=?57–91) in simulated gastric (0.1?N HCl, pH 1.2) and intestinal fluids (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only occurred for the SG compacts at the highest alcohol concentration in both media (f₂?=?35). The suitability of SG as a matrix former that can resist alcoholic effects therefore makes it suitable as an alternative polymer with wider applications for drug delivery.     

pH-Sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21?±?18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2?h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2?h, while nearly 90% of the drug was released within 6?h after transferring into SPDF.     

Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery

The purposes of this study were to develop and evaluate calcium pectinate/alginate microspheres (PAMs) and to exploit their pH-sensitive properties for colon-targeted delivery of encapsulated cisplatin. PAMs were prepared using an electrospraying method. The PAMs, as cores, were then coated with Eudragit S100 using a polyelectrolyte multilayer coating technique in aqueous solution. The morphology of the microspheres was observed under scanning electron microscopy. In vitro drug release studies were performed in simulated gastrointestinal fluid, and the results indicated that approximately 5 % of the cisplatin was released from the Eudragit S100-coated PAMs, and 51 % of the cisplatin was released from the uncoated PAMs at 1 h. The release of cisplatin from the Eudragit S100-coated PAMs was more sustained in simulated gastric fluid than in simulated intestinal fluid due to the increased solubility of the coating polymer in media with pH >7.0. Drug release from the Eudragit S100-coated PAMs was best described by the Higuchi’s square root model. From these results, it was concluded that Eudragit S100-coated PAMs are a potential carrier for delivery of cisplatin to the colon.     

Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system

Objective: Simple Eudragit microparticles loaded with prednisolone and chitosan-succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system.

Materials and methods: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions.

Results: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 μm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 μm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8.

Conclusions: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Preparation and Evaluation of pH‐Dependent Gradient‐Release Pellets for TCM

This paper is designed to investigate a novel sustained release system for Traditional Chinese Medicinal Compound Recipe (TCMCR) by incorporating three kinds of pH‐dependent gradient‐release coated pellets into capsules. In our study, dosage reform was conducted on the TCMCR model drug–Guanxin Suhe Wan (GSW), which is in the traditional form of honey bolus, comprising Styrax, Borneolumsyntheticum, Olbanum, Radix aristolochiae and Lignum santali albi. In this study, the β‐CD inclusion complexes were prepared separately for Styrax, Borneolumsyntheticum and the volatile oil extracted from the mixture of Olbanum, Radix aristolochiae and Lignum santali albi. Pellets were prepared in a centrifugal granulator using the powder layering technique and then divided into 3 equal weight portions and coated with HPMC, HPMCP HP‐55 and Eudragit L100/S100 to obtain gradient release in stomach, duodenum and jejunum or ileum respectively. On this basis, a pH‐dependent sustained‐release pellets system, “Guanxin Suhe Sustained‐release Capsules”(GSSC), was prepared by mixing the above three kinds of coated pellets at the weight ratio of 1:1:1. Pharmacokinetic (PK) studies between GSW and GSSC were made on male volunteers and isolated guinea pig hearts by plasma drug concentration method and serum pharmacology method respectively. In plasma drug concentration method, T_max was 0.42 h and 1.08 h for GSW and GSSC respectively, while in the serum pharmacology method, T_max was 0.56 h and 0.52 h respectively. The relative bioavailability of GSSC to GSW was 95.62% and 121.82% separately in the above two methods, indicating a similarity between the two methods in predicting the PK behavior of GSSC.     

Formulation and in Vitro and in Vivo Availability of Diclofenac Sodium Enteric-Coated Beads

Abstract

Diclofenac sodium enteric-coated beads were prepared using the conventional pan coating technique. Eudragit L₁₀₀ was used as a pH-dependent release-controlling polymer. The beads were evaluated for their particle size distribution, drug loading efficiency, flowability, in vitro release in 0.1 N HCI (pH 1.2) and phosphate buffer (pH 6.8), and bioavailability in beagle dogs relative to the commercial enteric-coated tablets Voltaren®. The beads showed a narrow particle size distribution in which 83% of the beads were in the range of 1-2 mm. The actual yield of the beads was 90.5% and their drug loading was 92%. The beads released about 8% of the drug during 2 hr of dissolution in 0.1 N HCI, and the commercial tablets released no drug. In phosphate buffer (pH 6.8) both formulations released their drug content in 1 hr. Both formulations are, therefore, in compliance with the USP requirements for release from enteric-coated dosage forms.

The in vivo availability study in six beagle dogs revealed that the formulated enteric-coated beads filled in hard gelatin capsules had a 197.54% bioavailability relative to that of the commercial Voltaren tablets. The tablets showed a significantly lower (p < 0.05) area under curve for 0—8 hr (AUC_{0-8 hr}) of 13.44 ± 15.02 μg hr/ml compared to 26.55 ± 5.19 μg hr/ml for the capsules. The capsules showed a nonsignificantly (p > 0.05) higher peak plasma concentration (C^max) of 6.77 ± 0.67 μg/ml compared to 5.88 ± 7.38 μg/ml for the tablets. The time to reach peak (T_max) values were 2 ± 1.48 and 2.25 ± 1.08 hr for the capsules and tablets, respectively. The capsules showed less interdog variability with respect to C_max (CV% 34.6) and AUC (CV% 19.55) compared to CV% 79.9 and 111.76, respectively, for the commercial tablets     

Preparation,structural characterisation and release study of novel hybrid microspheres entrapping nanoselenium,produced by green synthesis

The main goal of this study was to synthesise and characterise different formulations based on alginate and alginate/chitosan microspheres containing nanoselenium (nano‐Se) for controlled delivery applications. Nanosize elemental selenium was produced by using probiotic yogurt bacteria (Lactobacillus casei) in a fermentation procedure. The structural and morphological characterisation of the microspheres was performed by Fourier transform infrared (FTIR), X‐ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. FTIR and XRD pattern indicated that was an effective cross‐linking of selenium nanoparticles within the polymeric matrix in both cases. The SEM images reveal that selenium nanoparticles are mainly exposed on the surface of alginate, in contrast to porous structure of alginate/chitosan/nano‐Se, interconnected in a regular network. This architecture type has a considerable importance in the delivery process, as demonstrated by differential pulse voltammetry. Selenium release from both matrices is pH sensitive. Moreover, chitosan blended with alginate minimise the release of encapsulated selenium, in simulated gastric fluid, and prolong the duration of release in intestinal fluid. The overall effect is the enhancement of total percentage release concomitant with the longer duration of action. The authors’ formulation based on alginate/chitosan is a convenient matrix to be used for selenium delivery in duodenum, caecum and colon.Inspec keywords: organic‐inorganic hybrid materials, nanocomposites, blending, filled polymers, nanoparticles, nanofabrication, nanomedicine, biomedical materials, drug delivery systems, microorganisms, biological organs, selenium, polymer blends, fermentation, scanning electron microscopy, X‐ray diffraction, Fourier transform infrared spectra, surface morphology, nanoporous materials, porosity, pH, voltammetry (chemical analysis), encapsulationOther keywords: structural characterisation, hybrid microspheres entrapping nanoselenium, green synthesis, alginate‐chitosan microspheres, controlled delivery applications, nanosize elemental selenium, probiotic yogurt bacteria, Lactobacillus casei, fermentation, scanning electron microscopy, morphological characterisation, SEM, Fourier transform infrared spectra, FTIR, XRD, X‐ray diffraction, selenium nanoparticles, polymeric matrix, porous structure, differential pulse voltammetry, pH, blending, encapsulated selenium, simulated gastric fluid, intestinal fluid, total percentage release concomitant, duodenum, caecum, colon, Se     

Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate

Context: Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids.

Objectives: The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects.

Methods: Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis.

Results: SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study,?>?80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T_max?=?0.97?h, C_max?=?118.28?µg/mL of HSS; T_max?=?2.16?h, C_max?=?64.47?µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis.

Conclusions: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.     

Preparation and characterization of novel sinomenine microcapsules for oral controlled drug delivery

Background: Developing a sustained release drug to cure arthritis is needed. Sinomenine (SIN) is abstracted from sinomenium acutum and widely used in the treatment of various rheumatism and arrhythmia with few side effects. The primary aim of this study is to develop SIN microcapsules with polyelectrolyte multilayers for controlled drug release. Method: SIN microcrystals were encapsulated with chitosan, gelatin, and alginate by layer-by-layer technique, such as (gelatin/alginate)₄ and (chitosan/alginate)₆. The size distribution, zeta-potential, stability, and morphology of the microcapsules were characterized by a particle size analyzer, zetasizer, ultraviolet spectroscopy, and transmission electron microscope, respectively. The in vitro controlled release pattern of SIN was studied using a diffusion cell assembly at physiological pH of 6.8 or 1.4. Results: Light stability of these microcapsules was improved after microencapsulation. Compared with release rate of the SIN microcapsules coated by the poly(dimethyldiallyl ammonium chloride)/alginate and gelatin/alginate multilayers, release rate of the SIN microcapsules coated with chitosan/alginate multilayers was fast. Release rate progressively decreased with the increase of chitosan/alginate bilayer number and the decrease of pH value of release medium. Conclusion: These novel SIN microcapsules may be developed into oral controlled drug delivery for rheumatism and arthritis.     

Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm⁻¹. XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07°C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 μm. Storage of the microspheres at 40°C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.     

Preparation of the Traditional Chinese Medicine Compound Recipe Heart-Protecting Musk pH-Dependent Gradient-Release Pellets

ABSTRACT

In this study a sustained-release formulation of traditional Chinese medicine compound recipe (TCMCR) was developed by selecting heart-protecting musk pills (HPMP) as the model drug. Heart-protecting musk pellets were prepared with the refined medicinal materials contained in the recipe of HPMP. Two kinds of coated pellets were prepared by using pH-dependent methacrylic acid as film-forming material, which could dissolve under different pH values in accordance with the physiological range of human gastrointestinal tract (GIT). The pellets coated with Eudragit L30D-55, which dissolves at pH value over 5.5, were designed to disintegrate and release drug in the duodenum. The pellets coated with Eudragit L100–Eudragit S100 combinations in the ratio of 1:5, which dissolve at pH value 6.8 or above, were designed to disintegrate and release drug in the jejunum to ileum. The pellets coated with HPMC, which dissolves in water at any pH value, were designed to disintegrate and release drug in the stomach. Finally, the heart-protecting musk sustained-release capsules (HPMSRC) with a pH-dependent gradient-release pattern were prepared by encapsulating the above three kinds of coated pellets at a certain ratio in hard gelatin capsule. The results of dissolution of borneol (one of the active compounds of the TCMCR) in vitro demonstrated that the coating load and the pH value of the dissolution medium had little effect on the release rate of borneol from pellets coated with hydroxypropyl methyl cellulose (HPMC), but had a significant effect on the release rate of borneol from pellets coated with Eudragit L30D-55 or Eudragit L100–Eudragit S100 combinations in the ratio of 1:5. The pellets coated with Eudragit L30D-55 at 30% (w/w) coating load or above had little drug release in 0.1 mol/L HCl for 3 hr and started to release drug at pH value over 5.5. The pellets coated with Eudragit L100–Eudragit S100 combinations in the ratio of 1:5 at 36% (w/w) coating load or higher had little drug release in 0.1 mol/L HCl for 3 hr and in phosphate buffer of pH value 6.6 for 2 hr, and started to release drug at pH value 6.8 or above. The release profiles of lipophilic bornoel and hydrophilic total ginsenoside from HPMSRC, consisting of three kinds of pellets respectively coated at a certain ratio with HPMC, Eudragit L30D-55, and Eudragit L100–Eudragit S100 in the ratio of 1:5, showed a characteristic of pH-dependent gradient release under the simulated gastrointestinal pH conditions and no significant difference between them. The results indicated that various components with extremely different physicochemical properties in the pH-dependent gradient-release delivery system of TCMCR could release synchronously while sustained-releasing. This complies with the organic whole concept of compound compatibility of TCMCR.