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

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.     

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.     

Effects of guar gum content on structure and properties of multi-crosslinked polyurethane composite films

Films from multi-crosslinked polyurethane with different contents of guar gum (1–10 wt%) were prepared through a solution-casting method, followed by a thermal treatment or natural light exposure crosslinking procedure. Acrylic terminated prepolymers were prepared by capping the NCO groups of polyurethane prepolymers with pentaerythritol triacrylate. The effect of the guar gum content on the miscibility, morphology and physical properties of the blend films was investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, surface properties and tensile tests. The results reveal that small guar gum content is well embedded in the crosslinked polyurethane network and forms films with good mechanical properties, thermal behavior and hydrophilic properties. These results prove guar gum to be eco-friendly filler for multi-crosslinked polyurethane network. In the case of polyether urethanes, incorporating up to 3 wt% guar gum leads to a slight enhancement of the elongation at break, while for polyester urethanes incorporation up to 3 wt% guar gum slight increases stress at break values. Incorporating guar gum into the polyurethane networks leads to an increase in the hydrophilic nature of the polymer blends and improved surface structure. The properties of guar gum – which can be abundantly found in nature – make it desirable for polymer blends for biomedical applications.     

Preparation and evaluation of floating tablets of pregabalin

Abstract

Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p?>?0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12?h).     

Feasibility of xanthan gum–sodium alginate as a transdermal drug delivery system for domperidone

The present investigation comprises the formulation and in vitro evaluation of domperidone loaded transdermal drug delivery system (TDDS) for controlled release. The polymer membranes were prepared using xanthan gum (XG) and sodium alginate (SA) by varying the blends compositions viz., 10:0, 8:2, 6:4, 5:5, 4:6, 2:8, and 0:10 (XG/SA, wt/wt, %). The drug loaded membranes were evaluated for thickness, content uniformity, tensile behaviours, and in vitro drug release studies. Domperidone was found to be compatible with the prepared formulation as revealed by Fourier transform infrared (FTIR) spectroscopy studies. In vitro release studies were carried out in open glass diffusion cell for a period of 8 h and it showed controlled release of drug from the XG/SA matrix. The present study concludes that, the prepared transdermal films can be used to achieve controlled release of drug and improved bioavailability.     

Release of pentoxifylline from xanthan gum matrix tablets

Pentoxifylline-controlled release tablets were prepared using xanthan gum. The effects of polymer concentration, rotation speed, ionic strength, and pH of the dissolution medium on the release of the water-soluble pentoxifylline were studied. The release rate decreased with increasing polymer concentration in the tablet, which was reflected in the increase in the mean dissolution time. A higher rotation speed and increased ionic strength of the dissolution medium resulted in a higher rate of drug release of xanthan-based tablets. A higher release rate of pentoxifylline was also observed using acidic dissolution medium.     

Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of nicotine

Some naturally occurring biocompatible materials were evaluated as mucoadhesive controlled release excipients for buccal drug delivery. A range of tablets were prepared containing 0-50% w/w xanthan gum, karaya gum, guar gum, and glycol chitosan and were tested for swelling, drug release, and mucoadhesion. Guar gum was a poor mucoadhesive and lacked sufficient physical integrity for buccal delivery. Karaya gum demonstrated superior adhesion to guar gum and was able to provide zero-order drug release, but concentrations greater than 50% w/w may be required to provide suitable sustained release. Xanthan gum showed strong adhesion to the mucosal membrane and the 50% w/w formulation produced zero-order drug release over 4 hours, about the normal time interval between daily meals. Glycol chitosan produced the strongest adhesion, but concentrations greater than 50% w/w are required to produce a nonerodible matrix that can control drug release for over 4 hours. Swelling properties of the tablets were found to be a valuable indicator of the ability of the material to produce sustained release. Swelling studies also gave an indication of the adhesion values of the gum material where adhesion was solely dependent upon penetration of the polymer chains into the mucus layer.     

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.     

Polymorphism and drug release behavior of spray-dried microcapsules of sulfamethoxazole with polysaccharide gum and colloidal silica

Sulfamethoxazole microcapsules with polysaccharide gum, i.e. xanthan gum and guar gum, were prepared by employing a spray drying technique. The aqueous or the ammonium hydroxide solution of the gum containing the drug with or without colloidal silica was atomized with a centrifugal wheel atomizer rotated at 40000 rpm into a drying chamber held at 140±10°C. By formulation with colloidal silica, particle size of the resultant product increased, leading to improve the flowability and packability for the tableting. Polymorphic sulfamethoxazole mixture of Form I, II and III was produced in the formulation with cellulose acetate     

Studies of guar gum compression-coated 5-aminosalicylic acid tablets for colon-specific drug delivery

The aim of this study was to develop colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) using guar gum as a carrier. Core tablets containing 5-ASA were prepared by wet granulation with starch paste and were compression coated with coating formulations containing different quantities of guar gum (300, 200, 150, and 125 mg). In vitro drug release studies were carried out in simulated gastric and intestinal fluids and in pH 6.8 buffer containing rat cecal contents. The application of 175 mg of coating formulation containing 150 mg of guar gum over 5-ASA core tablets resulted in the release of less than 2% drug in simulated gastric and intestinal fluids and about 93% of 5-ASA in pH 6.8 buffer containing rat cecal contents. Differential scanning calorimetric (DSC) studies showed the absence of any interaction between 5-ASA and the excipients on storage at 45°C for 12 weeks. The study confirmed that selective delivery of 5-ASA to the colon can be achieved using guar gum as a carrier in the form of a compression coating over the drug core.     

Polymorphism and drug release behavior of spray-dried microcapsules of sulfamethoxazole with polysaccharide gum and colloidal silica

Abstract

Sulfamethoxazole microcapsules with polysaccharide gum, i.e. xanthan gum and guar gum, were prepared by employing a spray drying technique. The aqueous or the ammonium hydroxide solution of the gum containing the drug with or without colloidal silica was atomized with a centrifugal wheel atomizer rotated at 40000 rpm into a drying chamber held at 140±10°C. By formulation with colloidal silica, particle size of the resultant product increased, leading to improve the flowability and packability for the tableting. Polymorphic sulfamethoxazole mixture of Form I, II and III was produced in the formulation with cellulose acetate     

Polysaccharide matrices for microbially triggered drug delivery to the colon

Matrix tablets were prepared using xanthan gum (XG) and guar gum (GG) in varying proportions, and the suitability of the prepared tablets was evaluated for colon specific drug delivery. Indomethacin was used as a model drug. The ability of the prepared matrices to retard drug release in the upper gastrointestinal tract (GIT) and to undergo enzymatic hydrolysis by the colonic bacteria was evaluated. For this, drug release studies were carried out in the presence of rat cecal content. Further cecal content of rats with induced enzymatic activity were used. To ascertain the role of bacterial flora in carrying out the hydrolysis of the tablet, cecal content of rats treated with antibiotics were used in the dissolution media. Presence of XG in combination with GG in the tablets could retard drug release in the conditions of the upper GIT. However, the presence of GG and starch made these matrices microbially degradable. Guar gum alone as a drug release-retarding excipient in the matrices does not achieve the desired retardation. Presence of XG in the tablets not only retards the initial drug release from the tablets, but due to high swelling, makes them more vulnerable to digestion by the microbial enzymes in the colon.     

Development of extended zero-order release gliclazide tablets by central composite design

The purpose of this study was to develop an extended release tablet formulation containing gliclazide as a model drug by optimization technique. A central composite design was employed with pH-dependent matrix forming polymers like keltone-HVCR (X1) and eudragit-EPO (X2) as independent variables. Five dependent variables were considered: hardness, percent drug release after 1 hr, percent drug release after 6 hr, diffusion exponent and time required for 50% of drug release. Response surface methodology and multiple response optimization utilizing a quadratic polynomial equation were used to obtain an optimal formulation. The results indicate that Factor X1 along its interaction with Factor X2 was found to be significantly affecting the studied response variables. An optimized formulation, containing 8 mg of keltone-HVCR and 14.10mg of eudragit-EPO, provides a sufficient hardness (> 4.5 kg/cm2) and optimal release properties. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The release kinetics of gliclazide from optimized formulation followed zero-order release pattern. The dissolution profiles of optimized formulation before and after stability studies were evaluated by using similarity factor (f2) and were found to be similar. The results demonstrate the feasibility of the model in the development of extended release dosage form.     

Novel use of similarity factors f2 and Sd for the development of diltiazem HCl modified-release tablets using a 3(2) factorial design

The objective of this study was to develop modified-release tablets of diltiazem HCl using a direct compression technique. A 3² factorial design was employed using the amount of alkali-treated guar gum and cetyl alcohol as independent variables. This article proposes the use of a novel approach—f₂and S_d values as dependent variables—to evaluate the effect of selected independent variables along with other dependent variables (i.e., percentage drug released in x min, Y_x; time required for z% drug release, t_z; and mean dissolution time (MDT)). It is concluded that when a decision is to be made for the selection of a best batch, it is perhaps more realistic to use the f₂ or S_d value which takes into account the dissolution profile as a whole, as opposed to Y_x and t_z values which use just one point from the dissolution plot. The batch showing the f₂ value nearest to 100 or the S_d value nearest to zero is ranked as the best batch (diltiazem HCl 90 mg, alkali-treated guar gum 80 mg and cetyl alcohol 15 mg). The gel strength and matrix erosion of the formulated tablets were dependent on the type and amount of the adjuvants. The drug release rate is well correlated with matrix erosion. The kinetics of drug release fitted best to the Korsmeyer and Peppas model. It is concluded that by using a proper combination of the hydrophilic polymer and cetyl alcohol one can achieve a desirable drug release pattern.     

Rheological behavior of gel of xanthan with seed galactomannan: Effect of hydroalcoholic–ascorbic acid

The rheological properties of a physically linked hydroalcoholic gel obtained from a binary system consisting of xanthan and of galactomannan from the seeds of Mimosa scabrella (X:GB) with a low Man:Gal ratio of 1.1:1 were compared to those of guar gum (Man:Gal ratio 1.5:1, X:GG). The rheological analysis demonstrated an improvement of strength of X:GB and X:GG hydrogels after dispersion of the polysaccharides in buffer with 1,2-propanediol. The addition of ascorbic acid to these hydrogel formulations resulted in a slight decrease of gel strength. Both hydrogels presented rheological stability over 12 weeks at ambient temperature.     

Evaluation of Xanthan Gum in the Preparation of Sustained Release Matrix Tablets

The objective of this study was to evaluate xanthan gum as a matrix former for the preparation of sustained release tablets. Preliminary experiments indicated that a fine particle sue of xanthan gum produced the slowest and most reproducible release profiles. Based on single surface experiments and tablet erosion studies, it was concluded that release of a soluble drug (chlorpheniramine maleate) and an insoluble drug (theophylline) from tablets containing low concentraions of xanthan gum was mainly via diffusion and erosion, respectively. Drug release from tablets containing xanthan gum was slightly faster in acidic media due to more rapid initial surface erosion than at higher pH. After hydration of the gum, drug release was essentially pH-independent. The amount released was directly proportional to the loading dose of drug and inversely proportional to gum concentration in tablets. Release profiles of chlorpheniramine maleate and theophylline remained unchanged after three months storage of the tablets at 40°C/80% RH and 40°C. Model tablets containing 5% xanthan gum exhibited release profiles similar to tablets containing 15% hydroxypropyl methylcellulose.     

Tailoring the Release Rates of Fluconazole Using Solid Dispersions in Polymer Blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Tailoring the release rates of fluconazole using solid dispersions in polymer blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Effect of polymer molecular weight and of polymer blends on the properties of rapidly gelling nasal inserts

The objective was to investigate the potential of polymer molecular weight (MW) and polymer blends for the control of drug release from in situ gelling nasal inserts prepared by lyophilization of solutions of model drugs (oxymetazoline HCl, diprophyllin) and polymers. Drug release, polymer solution viscosity, water uptake and mass loss, mechanical properties, and bioadhesion potential were measured. Sonication was effective to reduce the viscosity/polymer MW of carrageenan solutions. Nasal inserts prepared from sonicated carrageenan showed an insignificant reduction in water uptake with sonication time and no disintegration of the gel matrix. In contrast, inserts of different MW Na-alginates revealed a reduced water uptake and an increased mass loss with lower MW. Inserts prepared from carrageenan/low MW Na-alginate blends took up more water at a higher low MW Na-alginate content. Sonicated carrageenan inserts released oxymetazoline HCl independent of the sonication time and diprophyllin with only a slight reduction in the release rate. Release of both drugs from Na-alginate inserts was slow from high MW inserts because no insert dissolution occurred. Increasing the Na-alginate content of inserts prepared from polymer blends accelerated the drug release enabling release rates over a broad range. The bioadhesion potential of Na-alginate inserts was strongly reduced for the low MW grades because of dissolution of the inserts. Xanthan gum and Carbopol 971 blended with Na-alginate formed inserts with poor bioadhesion. The use of polymer blends to control the drug release from nasal inserts was superior to the use of polymers of different MW.