Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit? S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In?vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit? S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.     

Potential of calcium pectinate beads for target specific drug release to colon

A pectin-based colon specific delivery system bearing 5-fluorouracil (5-FU) was developed for effective delivery of drug to the colon. Calcium pectinate gel (CPG) beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S-100. The CPG beads formed were spherical with smooth surfaces. CPG beads size was found to be in the range of 1.32+/-0 . 12-1.88+/-0.08 mm. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Release in PBS (pH 7.4) and simulated gastric fluid showed almost similar pattern and rate, whereas a significant increase in percent cumulative drug release (58.3+/-1.36%) was observed in medium containing rat caecal content, i.e. the amount of the drug released from the formulation was found to be 49.2+/-2.29 and 58.3+/-1.36% of drug with 2 and 4% w/v caecal matter after 24 h whereas in control study 33.2+/-1.19% of drug was released. Moreover, to induce the enzymes that specifically act on pectin, the rats were treated with 1 ml of 1% w/v dispersion of pectin for 2 and 4 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of caecal matter. A marked improvement in the drug release was observed in presence of caecal matter obtained after induction when compared to those without induction. The percentage of drug released after 24 h release was observed to be 69.3+/-2.81 and 86.7+/-3.15%, respectively, with 2 and 4% w/v rat caecal matter obtained after 2 days of enzyme induction, and 82.4+/-3.15 and 98.7+/-4.26%, respectively, after 4 days of enzyme induction. In vivo data showed that Eudragit S-100 coated calcium pectinate beads delivered most of its drug load (93.2+/-3.67%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally-administered 5-FU loaded Eudragit S-100 coated calcium pectinate beads can be used effectively for the specific delivery of drug to the colon.     

Chitosan hydrochloride based microspheres of albendazole for colonic drug delivery

Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver albendazole specifically into the colon. Microspheres were prepared by an emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration, stirring rate and concentration of cross-linking agent on the particle size and drug loading was studied. With an increase in CH concentration, the average particle size was increased. Increased agitation speed reduced the size of the microspheres but higher agitation speed resulted in irregularly shaped microspheres. Increasing the concentration of cross-linking agent produced more regularly shaped microspheres of smaller size. The drug loading was highest at a drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of cross-linking agent. The effect of CH concentration on in vitro drug release from the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro drug release study of the optimized formulation was carried out in simulated colonic fluid, with and without 2% rat caecal content. The drug release in 24 h was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid with rat caecal contents.     

Potential of guar gum microspheres for target specific drug release to colon

Various approaches for colon targeted drug delivery have been studied over the last decade including, pro-drugs, timed-released systems, coating of pH-dependant polymer and the use of polysaccharides. In the present work, a novel formulation consisting of cross-linked microspheres of guar gum has been investigated for colon-targeted delivery of metronidazole. An emulsification method involving the dispersion of aqueous solution of guar gum in castor oil was used to prepare spherical microspheres. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Placebo microspheres exhibited a smooth surface while the incorporation of drug imparted a slight roughness to the surface texture. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The in vitro drug release studies were performed in simulated gastric fluid for 2 h and intestinal fluid for 3 h, which revealed that the drug was retained comfortably inside the microspheres and that only 15.27+/-0.56% of the drug was released in 5 h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat cecal contents, which showed improved drug release. Moreover, to induce the enzymes that specifically act on guar gum, the rats were treated with 1 ml of 1% w/v dispersion of guar gum for 2, 4 and 6 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of cecal matter. A marked improvement in the drug release was observed in presence of cecal matter obtained after induction when compared to those without induction. In vitro release studies exhibited 31.23+/-1.49% drug release in 24 h in dissolution medium without rat cecal matter. However, the incorporation of 4% w/v cecal matter obtained after 6 days of enzymes induction increased the drug release to 96.24+/-4.77%.     

Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate

The aim of the research work was to develop cyst-targeted novel concanavalin-A (Con-A) conjugated mucoadhesive microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Eudragit microspheres of DF were prepared using emulsification-solvent evaporation method. Formulations were characterized for particle size and size distribution, % drug entrapment, surface morphology and in vitro drug release in simulated gastrointestinal (GI) fluids. Eudragit microspheres of DF were conjugated with Con-A. IR spectroscopy and DSC were used to confirm successful conjugation of Con-A to Eudragit microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to colonic mucosa and Con-A conjugation efficiency with microspheres. IR studies confirmed the attachment of Con-A with Eudragit microspheres. All the microsphere formulations showed good % drug entrapment (78+/-5%). Zeta potential of Eudragit microspheres and Con-A conjugated Eudragit microspheres were found to be 3.12+/-0.7mV and 16.12+/-0.5mV, respectively. Attachment of lectin to the Eudragit microspheres significantly increases the mucoadhesiveness and also controls the release of DF in simulated GI fluids. Gamma scintigraphy study suggested that Eudragit S100 coated gelatin capsule retarded the release of Con-A conjugated microspheres at low pH and released microspheres slowly at pH 7.4 in the colon.     

Evaluation of potential of Zn-pectinate gel (ZPG) microparticles containing mesalazine for colonic drug delivery

BACKGROUND AND THE PURPOSE OF THE STUDY: Pectin derivatives have been utilized for colonic drug delivery (CDD). In this study the effects of different formulation variables upon the characteristics of pectinate microparticles (MPs) prepared by ionotropic gelation technique for colonic delivery of mesalazine was investigated. METHODS: In-vitro drug release of MPs was studied using USP XXIV dissolution apparatus type I, in different fluids e.g. simulated gastric fluid (SGF: pH 1.2), simulated intestinal fluid (SIF: pH 7.4), and simulated colonic fluid (SCF: pH 6.8) of volume 900 ml, at 100 rpm maintained at 37±0.2°C. This study was also performed in the presence of 4% w/v rat caecal content (RCC) using phosphate buffer saline (pH 6.8) as SCF. Gamma scintigraphy study was performed on New Zealand rabbit animal model using (99m) Tc. RESULTS: The results showed that maximum entrapment of mesalazine (86.1±1.7%) and strength of gel network zinc pectinate gel microparticles (ZPGD2) was achieved in cross-linking solution of pH 1.6. Batch of ZPGD2 showed least swelling ratio and drug release. In RCC medium the t(50%) value of CPG-MPs was 3-4 folds greater than ZPG-MPs. Scintigram showed the residence of ZPG-MPs (filled in enteric coated capsule) in colon more than 9 hrs and delivery of almost all the drug loading dose in colon. MAJOR CONCLUSION: The results of this study suggest the designed formulation of ZPG-MPs has the potential to serve as a colonic drug delivery system.     

Design and Development of Multiparticulate System for Targeted Drug Delivery to Colon

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit® L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit® microspheres, forming a multireservoir system. By coating the microspheres with Eudragit® pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit® starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents.     

Design and development of multiparticulate system for targeted drug delivery to colon

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit® L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit® microspheres, forming a multireservoir system. By coating the microspheres with Eudragit® pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit® starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents.     

Preparation and characterization of floating drug delivery system of azithromycin

The objective of present study was to develop a stomach drug delivery system of azithromycin (AZH) as a model drug for eradication of Helicobacter pyloni (H. pylori). Floating microspheres of AZH were prepared by the solvent evaporation method. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy and in vitro drug release characteristics. The formulations were prepared at a variable stirring rate (300 to 500 rpm) and temperature (30-50 degrees C). Surface morphology characteristics were studied using scanning electron microscopy (SEM). The mean particle size of the microspheres significantly increased with increasing polymer concentration and was in the range 252.26 +/- 6.50 to 380.91 +/- 4.59 microm. Angle of repose was between 26.42 to 35.83 degrees. Tapped density ranged between 0.493 to 0.612 g/cm3. The compressibility index of all formulations was found to be in the range of 12.41 to 17.16%, which was < 20 indicating good flow characteristics. The encapsulation efficiency of the prepared microspheres was in the range of 27.8 +/- 4.30 to 66.23 +/- 2.08%. The physical state of the drug, before and after formulation was determined by differential scanning calorimetry (DSC). Percentage buoyancy of the microspheres was in the range 45.52 +/- 0.69 to 68.71 +/- 0.61% for 8 h. In vitro drug release studies were performed in simulated gastrointestinal fluid (SGF), pH 2.0 as dissolution medium (900 mL) for 8 h. Effects of stirring rate during preparation, polymer concentration and temperature on the size of microspheres and drug release were also observed. The results of the present studies indicated that the floating microspheres of AZH were formulated to provide site specific delivery of drug with a view to provide an effective and safe therapy for eradication of H. pylori with a reduced dose and reduced duration of therapy.     

Potential of Guar Gum Microspheres for Target Specific Drug Release to Colon

Various approaches for colon targeted drug delivery have been studied over the last decade including, pro-drugs, timed-released systems, coating of pH-dependant polymer and the use of polysaccharides. In the present work, a novel formulation consisting of cross-linked microspheres of guar gum has been investigated for colon-targeted delivery of metronidazole. An emulsification method involving the dispersion of aqueous solution of guar gum in castor oil was used to prepare spherical microspheres. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Placebo microspheres exhibited a smooth surface while the incorporation of drug imparted a slight roughness to the surface texture. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The in vitro drug release studies were performed in simulated gastric fluid for 2 h and intestinal fluid for 3 h, which revealed that the drug was retained comfortably inside the microspheres and that only 15.27±0.56% of the drug was released in 5 h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat cecal contents, which showed improved drug release. Moreover, to induce the enzymes that specifically act on guar gum, the rats were treated with 1 ml of 1% w/v dispersion of guar gum for 2, 4 and 6 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of cecal matter. A marked improvement in the drug release was observed in presence of cecal matter obtained after induction when compared to those without induction. In vitro release studies exhibited 31.23±1.49% drug release in 24 h in dissolution medium without rat cecal matter. However, the incorporation of 4% w/v cecal matter obtained after 6 days of enzymes induction increased the drug release to 96.24±4.77%.     

Development and characterization of colon specific drug delivery system bearing 5-ASA and camylofine dihydrochloride for the treatment of ulcerative colitis

The treatment of ulcerative colitis (inflammatory bowel disease, IBD) has been achieved by using colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride. Chitosan microspheres were prepared separately for both the drugs using emulsion method followed by enteric coating with Eudragit^®S-100. The in vitro drug release was investigated in different simulated GIT medium. The drug release in PBS (pH7.4) and simulated gastric fluid has shown almost similar pattern and rate, whereas a significant increase in drug release (70.3?±?1.36 and 72.5?±?1.33% of 5-ASA and Camylofine, respectively) was observed in medium containing 3% rat caecal matter, after 24?h. In control study, 57.1?±?1.13% of 5-ASA and 59.2?±?1.2% of Camylofine release was observed in 24?h. For enzyme induction, rats were orally administered with 1?mL of 1% w/v dispersion of chitosan for 5 days and release rate studies were conducted in SCF with 3% w/v of caecal matter. An enhanced drug release (i.e., 92.3?±?3.81 and 95.5?±?3.52% 5-ASA and Camylofine, respectively) was observed after 24?h in dissolution medium containing 3% caecal content obtained from enzyme induced animals. In vivo data showed that microspheres delivered most of its drug load (76.55?±?2.13%) to the colon after 9?h, which reflects its targeting potential to the colon. It is concluded that orally administered microspheres of both drugs can be used together for the specific delivery of drug to the colon and reduce symptoms of ulcerative colitis.     

牛血清白蛋白阳离子微球的制备及体外评价

目的制备牛血清白蛋白（BSA）口服阳离子微球,考察天然阳离子物质壳聚糖（CHS）的加入对蛋白微球的粒径、电动电势、包封率、载药量及体外释放情况的影响。方法以乳酸／羟基乙酸共聚物（PLGA）和壳聚糖（CHS）为载体材料,采用W／O／W复乳-溶剂挥发法制备牛血清白蛋白乳酸／羟基乙酸共聚物-壳聚糖（PLGA／CHS）阳离子微球。通过正交设计优化制备工艺,确定最佳处方。建立准确而简便的蛋白含量测定方法,并对微球进行体外评价。结果最佳处方为：BSA浓度为150g·L^-1、PLGA浓度为8％、外水相体积为80mL、壳聚糖浓度为0．2％。制得的微球形态圆整,平均粒径为（6．9±5．5）μm,为表面荷正电的阳离子微球[ζ电势=00．0±0．6）mV],包封率为（75．4±4．6）％,载药量为（9．3±0．2）％。体外释放结果表明,在模拟胃液和模拟肠液中,壳聚糖的加入均能减少突释,延缓药物的释放。结论与PLGA微球相比,制得的PLGA／CHS阳离子微球表面带正电,具有较高的包封率和载药量,可以延缓药物释放,同时减少突释现象。     

Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit® S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4229–4236, 2009     

Low molecular weight heparin loaded pH-sensitive microparticles

Low molecular weight heparins (LMWH) have shown efficacy in the treatment of inflammatory bowel disease after parenteral administration however risking severe hemorrhagic adverse effects. Therefore, an oral colonic targeted heparin dosage form allowing the release of LMWH directly in the inflamed tissue would be of major interest. Enoxaparin was entrapped into pH-sensitive microspheres using Eudragit P4135F that dissolves at pH>7.2. Particle preparation was based on a double emulsion technique with either solvent extraction or evaporation. In order to increase the entrapment efficacy several preparation parameters were optimized, such as inner phase volume, polymer concentration, stabilization of the internal interface by surfactants. Solvent evaporation led to higher entrapment rates (evaporation: 70.1+/-9.9%; extraction: 46.5+/-6.4%). When increasing the volume of the inner aqueous heparin phase, lower encapsulation rates and larger microspheres ( approximately 100-400 microm) were obtained. Sorbitan monostearate (1.75-28% of the total particle mass) had a stabilizing effect on the primary water/oil emulsion. Indeed, higher encapsulation rates (7%: 78.2+/-3.5%; 14%: 76.4+/-10.1%) and smaller particles ( approximately 120-160 microm) were obtained whereas hexadecyltrimethylammonium bromide destabilized the primary emulsion. Interfacial tension studies at a simulated internal water/oil interface confirmed these results. As expected, in vitro drug release was found to be strongly pH-dependent; LMWH was retained in microspheres at pH<6 (<20% release within 4h) whereas a fast drug release was obtained at pH 7.4. The developed microspheres exhibited a particle size adapted to the needs of inflammatory bowel disease therapy, an efficient LMWH encapsulation, and a pH-controlled drug release. These microspheres represent a promising tool for the selective oral delivery of heparin to the colon, especially interesting in the treatment of inflammatory bowel disease.     

Pectin/Ethylcellulose as film coatings for colon-specific drug delivery: preparation and in vitro evaluation using 5-fluorouracil pellets

The aim of the present study is to develop colon-targeted drug delivery systems for 5-fluorouracil using pectin combined with ethylcellulose as a film coat with fluidized bed coater. Pellets (0.8-1.0 mm in diameter) containing 40% 5-fluorouracil and 60% microcrystalline cellulose were prepared by extrusion and spheronization. Film-coated pellets of 5-fluorouracil containing various proportions (1:0, 0:1, 1:1, 1:2, w/w) of pectin and ethylcellulose (Surelease) were prepared and subjected to in vitro drug release. The amount of 5-fluorouracil released from pellets at different time intervals was estimated by high-performance liquid chromatography. Drug release was assessed using flow testing in the presence and absence of rat caecal contents. The film thickness is expressed as the theoretical percentage of the weight gained (TWG-%) used relative to the weight of the coated pellets. Coated pellets with pectin alone and TWG-20% released 100% of the 5-fluorouracil in the simulated gastric and small intestinal conditions and failed to control the drug release in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions; while coated pellets with ethylcellulose alone and TWG-20% released 11.7 +/- 0.9% of the 5-fluorourail at the end of 24 h. When the ratio of pectin to Surelease was 1:1 (w/w) and film coat TWG-20%, the release was rapid and was accompanied by splitting of the coat. When the ratio of pectin to Surelease was 1:2 (w/w) and film coat TWG-13% and TWG-20%, the formulations released 9.8 +/- 0.7% and 4.1 +/- 0.4%, respectively, of 5-fluorouracil in the first 5 h of the dissolution study in the simulated gastric and small intestinal conditions. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) for another 19 h, the film coat with the formulations of TWG-13% and TWG-20% released 96 +/- 1.3% and 85.0 +/- 0.3%, respectively, of 5-fluorourail in simulated colonic fluids at the end of 24 h of the dissolution study, whereas in the control study the formulations released 51.4 +/- 1.0% and 34 +/- 0.5%, respectively, of 5-fluorouracil in absence of rat caecal contents at the end of 24 h. The results of the study show that the formulation of TWG-20% (pectin to Surelease 1:2, w/w) is most likely to provide targeting of 5-fluorouracil for local action in the colon, as it released only 4.1 +/- 0.4% of the drug in the simulated gastric and small intestinal conditions, and it released 85.0 +/- 0.3% of 5-fluorourail in simulated colonic fluids at the end of 24 h. The 5-fluorouracil-coated pellets showed no change in physical appearance, drug content, or dissolution pattern after storage at 40 degrees C/75% relative humidity for 6 months. Differential scanning calorimetric study indicated no possibility of interaction between 5-fluorouracil and pectin or other excipients used in the coated pellets.     

Alginate microspheres of isoniazid for oral sustained drug delivery

In the present study, spherical microspheres able to prolong the release of INH were produced by a modified emulsification method, using sodium alginate as the hydrophilic carrier. The shape and surface characteristics were determined by scanning electron microscopy using gold sputter technique. Particle sizes of both placebo and drug-loaded formulations were measured by SEM and the particle size distribution was determined by an optical microscope. The physical state of the drug in the formulation was determined by differential scanning calorimetry (DSC). The release profiles of INH from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of microspheres on oral administration and the extent of transit through the gastrointestinal tract (GIT). The microspheres had a smoother surface and were found to be discreet and spherical in shape. The particles were heterogeneous with the maximum particles of an average size of 3.719mum. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate microspheres were found to possess good bioadhesion (72.25+/-1.015%). The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4h and were detectable in the intestine 24h post-oral administration, although the percent radioactivity had significantly decreased (t(1/2) of (99m)Tc=4-5h). Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of INH was released in SGF pH 1.2 in 6h and 71.25% in SIF pH 7.4 in 30h. No significant drug-polymer interactions were observed in FT-IR studies. Dissolution and gamma-scintigraphy studies have shown promising results proving the utility of the formulation for enteric drug delivery.     

Evaluation of diltiazem hydrochloride-loaded mucoadhesive microspheres prepared by emulsification-internal gelation technique

The problems of frequent administration and variable low bioavailability (40-60%) after oral administration of conventional dosage forms of diltiazem can be attenuated by designing it in the form of mucoadhesive microspheres which would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance the bioavailability. Diltiazem-loaded mucoadhesive microspheres were successfully prepared by emulsification-internal gelation technique with a maximum incorporation efficiency of 93.29 +/- 0.26%. The scanning electron microscopic study indicated that the microspheres were spherical in shape and the drug remained dispersed in the polymer matrix at amorphous state, which was further confirmed by x-ray diffraction analysis. The in vitro wash-off test indicated that the microspheres had good mucoadhesive properties. The wash-off was faster at simulated intestinal fluid (phosphate buffer, pH 7.4) than that at simulated gastric fluid (0.1 M HCl, pH 1.2). The in vitro drug release mechanism was non-fickian type controlled by swelling and relaxation of polymer. There was no significant change in drug content and cumulative drug release of drug-loaded microspheres stored at different storage condition after 8 weeks of study.     

Release characteristics of pectin microspheres prepared by an emulsification technique

The potential application of pectin as a matrix polymer for making microspheres by an emulsification technique was explored, and the drug release property of these pectinate microspheres containing drug cores of varying aqueous solubilities: sulphanilamide, sulphaguanidine and sulphathiazole, was investigated using different dissolution media. The size and size distribution, specific surface area, drug content and drug release property of the pectinate microspheres were determined. The solubility and solution pH of drugs and their propensity to interact with pectin were characterized. Pectinate microspheres were successfully prepared by external gelation, using a modified emulsification technique. The kinetics of drug release from the microspheres best fitted Higuchi's model. Interestingly, the lowest percentage of drug released was produced by microspheres which were smallest in size and, therefore, largest in specific surface area, and containing sulphanilamide, the most aqueous soluble and the lowest molecular weight drug. Mathematical correlation study indicated that the drug release profile of pectinate microspheres was notably affected by the drug content and the extent of drug-pectin interaction in the microspheres. Generally, a higher percentage of drug was released from the microspheres with a higher drug content and/or lower extent of drug-pectin interaction. The extent of drug-pectin interaction was highest in microspheres containing sulphanilamide, followed by sulphaguanidine and sulphathiazole, opposite to that of drug content.     

Release characteristics of pectin microspheres prepared by an emulsification technique

The potential application of pectin as a matrix polymer for making microspheres by an emulsification technique was explored, and the drug release property of these pectinate microspheres containing drug cores of varying aqueous solubilities: sulphanilamide, sulphaguanidine and sulphathiazole, was investigated using different dissolution media. The size and size distribution, specific surface area, drug content and drug release property of the pectinate microspheres were determined. The solubility and solution pH of drugs and their propensity to interact with pectin were characterized. Pectinate microspheres were successfully prepared by external gelation, using a modified emulsification technique. The kinetics of drug release from the microspheres best fitted Higuchi's model. Interestingly, the lowest percentage of drug released was produced by microspheres which were smallest in size and, therefore, largest in specific surface area, and containing sulphanilamide, the most aqueous soluble and the lowest molecular weight drug. Mathematical correlation study indicated that the drug release profile of pectinate microspheres was notably affected by the drug content and the extent of drug-pectin interaction in the microspheres. Generally, a higher percentage of drug was released from the microspheres with a higher drug content and/or lower extent of drug-pectin interaction. The extent of drug-pectin interaction was highest in microspheres containing sulphanilamide, followed by sulphaguanidine and sulphathiazole, opposite to that of drug content.     

Cross-linked guar gum hydrogel discs for colon-specific delivery of ibuprofen: formulation and in vitro evaluation

Hydrogel discs of guar gum cross-linked with glutaraldehyde were prepared as vehicles for colon-specific drug delivery. Ibuprofen was chosen as model drug. The discs were evaluated for such parameters as size, shape, weight, and drug loading. Swelling (buffer uptake) and in vitro drug release study, in presence and absence of rat caecal contents, was performed in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.4) to evaluate the effect of various formulation parameters like guar gum concentration, amount of cross-linking agent, and cross-linking time on drug release. Cross-linking resulted in significant reduction in swelling of guar gum. Significant increase in drug release was observed in medium containing rat caecal content. Percent drug release increased with increasing glutaraldehyde concentration. Cross-linking time and guar gum concentration did not have any significant effect on drug release in the range studied.