Kinetics and Thermodynamics of Drug Permeation Through Silicone Elastomers (II) Effect of Penetrant Lipophilicity

The permeation of testosterone analogs through silicone membranes was studied. The variation in the lipophilicity of testosterone molecules was accomplished by the addition or elimination of methyl group and the formation of ester. Furthermore, the effects of replacing one of the CH₃ groups on the dimethylsiloxane unit in the silicone polymer chains by a polar CH₂CH₂CF₃, group, which changes polymer characteristics and thus affects the membrane permeability, was investigated as well. It was found that potential which might prevent flocculation altogether. This can lead to caking. The lowest concentration effective in prevent ing coagulum formation should be used.

Suspensions made from a fluid aluminum hydroxide concentration were easy to redisperse after six weeks of storage. The sedimentation volume was 0.64. Addition of 0.2% xanthan gum raised the sedimentation volume to a value of 1.0. There was no evidence of coagulum formation in this system.     

Oral Controlled Release Formulation for Highly Water‐Soluble Drugs: Drug–Sodium Alginate–Xanthan Gum–Zinc Acetate Matrix

An oral controlled release formulation matrix for highly water‐soluble drugs was designed and developed to achieve a 24‐hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH7.5) and simulated gastric fluid (SGF, pH1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24‐hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl–sodium alginate–xanthan gum–zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross‐linking structure. The cross‐linking structure might control a highly water‐soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.     

Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix

An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH7.5) and simulated gastric fluid (SGF, pH1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl-sodium alginate-xanthan gum-zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.     

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     

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     

Kinematic Viscosity and Density of Binary and Ternary Mixtures Containing Hydrocolloids,Sodium Chloride,and Water

The kinematic viscosity and density of binary aqueous solutions containing xanthan gum and ternary aqueous solutions containing carboxymethyl cellulose and sodium chloride have been measured from 303 K to 318 K at different values of pH. The viscosity and density for binary and ternary systems showed increases with a higher concentration of hydrocolloids (xanthan gum or carboxymethyl cellulose) and reductions with increasing temperature. The presence of NaCl in the ternary systems produced an electro-viscous effect that influenced the viscosity and density of the system. The models used to predict the viscosity, density, and apparent specific volume demonstrated satisfactory results in comparisons with experimental data.     

The containment of oil spills in porous media using xanthan/aluminum solutions, gelled by gaseous CO2 or by AlCl3 solutions

The gelation in situ of polymers may be a method for temporarily containing organic solvents and other petroleum derived products, which may enter the subsurface. In order to create gels that are neither toxic to humans nor to the ecosystem, we have investigated on the use of the biopolymer xanthan gum with aluminum as a crosslinking agent. Firstly we have considered xanthan/sodium aluminate solutions, which upon preparation are strongly basic and do not gel. The gelation takes place in acid solutions so that Al(III) ions are released, and is instantaneous. Therefore, a special technique must be used for generating the gel structure in situ. The un-gelled solution must be injected and an acid must be added afterwards. We have investigated on the gelling reaction induced by gaseous carbon dioxide, which is an acid gas. The insufflation of CO(2) above the solution generates a layer of gel whose thickness progressively increases as CO(2) diffuses in the polymer solution. Secondly we have investigated on the use of aluminum chloride as the source of Al(III) ions. Also in this case, due to the full availability of Al(III) ions, the gelling reaction would be instantaneous. Therefore, the solution of AlCl(3) must be added on the top of the xanthan solution after its injection. For both gelling systems we have studied both theoretically and experimentally the rate of formation of the gel layer which progressively thickens after the insufflation of CO(2) or after the addition of the AlCl(3) solution.     

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.     

Xanthan Gum and Alginate Based Controlled Release Theophylline Formulations

The oral absorption of theophylline from two sustained release formulations, formulated using xanthan gum or sodium alginate, has been investigated in the beagle dog. A commercial product was used for comparison. Dissolution tests and an in vivo dog study both indicated that the xanthan gum tablet released drug at a constant rate and performed as a pH independent zero-order controlled release formulation. With the alginate tablet, faster dissolution rates were observed when acid medium was present. The pH dependent release behavior of the alginate formulation is explained. Drug release mechanisms which are influenced by the gel behaviors in these two polymers are discussed. The relative oral bioavailabilities of these two formulations in dog were 74-84% compared to immediately releasing capsules, and three-fold that of the commercial product with an equivalent dose.     

Relationship of dissolution rate in anionic polymeric solutions to viscosity

The influence of viscosity on the dissolution rate of m-acetotoluidide in aqueous solutions of acacia, gelatin type B, sodium carboxymethylcellulose, sodium alginate and xanthan gum was investigated. The viscosity was measured by a rotational viscometer. The dissolution rates decreased as the viscosities of solutions of anionic polymers increased. The curves representing the relationship of dissolution rate and viscosity varied for each polymeric solution depending on the structural characteristics of the polymer.     

Xanthan Gum and Alginate Based Controlled Release Theophylline Formulations

Abstract

The oral absorption of theophylline from two sustained release formulations, formulated using xanthan gum or sodium alginate, has been investigated in the beagle dog. A commercial product was used for comparison. Dissolution tests and an in vivo dog study both indicated that the xanthan gum tablet released drug at a constant rate and performed as a pH independent zero-order controlled release formulation. With the alginate tablet, faster dissolution rates were observed when acid medium was present. The pH dependent release behavior of the alginate formulation is explained. Drug release mechanisms which are influenced by the gel behaviors in these two polymers are discussed. The relative oral bioavailabilities of these two formulations in dog were 74–84% compared to immediately releasing capsules, and three-fold that of the commercial product with an equivalent dose.     

Mechanochemical synthesis of a hydroxycarbonate form of layered magnesium aluminum hydroxides

Mechanical activation of a mixture of magnesium hydroxide, aluminum hydroxide, and sodium bicarbonate in an AGO-2 planetary mill, followed by water washing leads to the formation of a layered magnesium aluminum hydroxide. The double hydroxide obtained at a magnesium hydroxide to aluminum hydroxide ratio of 3:1 is essentially phase-pure and contains both carbonate and bicarbonate ions in its interlayer spaces. The synthesized double hydroxide was characterized by x-ray diffraction, IR spectroscopy, thermogravimetry, differential thermal analysis, and chemical analysis.     

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.     

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.     

脱脂奶粉分散稳定性的实验研究

粉体的分散稳定性对粉体的加工、贮存及品质有重要影响。以脱脂奶粉及其添加剂(黄原胶和β-环糊精)为模型材料,研究了非晶态粉体分散稳定性的影响因素及评价方法。应用流变仪测定了脱脂奶粉及其与添加剂混合物的结块性能,考察了贮存时间和组成对结块性能的影响。结果表明:脱脂奶粉的结块倾向随时间的延长而增加;添加黄原胶可明显改善脱脂奶粉的分散稳定性,但添加β-环糊精的效果不明显,而黄原胶和β-环糊精复配型添加剂对提高脱脂奶粉的分散稳定性效果最好。     

Statistical evaluation of influence of xanthan gum and guar gum blends on dipyridamole release from floating matrix tablets

The present investigation explored the use of xanthan gum and guar gum for development of floating drug delivery system of dipyridamole using factorial design approach. The content of polymer blends (X(1)) and ratio of xanthan gum to guar gum (X(2)) were selected as independent variables. The diffusion exponent (n), release rate constant (k), percentage drug release at 1 hr (Q(1)) and 6 hr (Q(6)) were selected as dependent variables. Tablets of all batches had desired buoyancy characteristics. Multiple regression analysis with two way ANOVA revealed that both the factors had statistically significant influence on the response studied (p<0.05). Results of Tukey test showed the relative contribution of each level of different factors for the response studied. It was concluded that the ratio of xanthan to gaur gum had equal or dominant role as controlling factor on kinetics of drug release compared to content of polymer blends.     

Curcumin containing monoolein aqueous dispersions: A preformulative study

The present study describes the production and characterization of monoolein aqueous dispersions (MAD) as drug delivery systems for curcumin (CR).MAD based on monoolein and different emulsifiers have been produced and characterized. Morphology and dimensional distribution have been investigated by Cryogenic Transmission Electron Microscopy (cryo-TEM), X-ray and Photon Correlation Spectroscopy (PCS).Monoolein in different mixtures with sodium cholate, sodium caseinate, bentonite and poloxamer resulted in heterogeneous dispersions constituted of unilamellar vesicles, cubosomes and sponge type phases, depending on the employed components, as found by cryo-TEM and X-ray studies. CR was encapsulated with entrapment efficiencies depending on the MAD composition, particularly the highest was reached in the case of monoolein/poloxamer/sodium cholate mixture. The same mixture was able to maintain CR stability also after 6 months.CR release modalities were in vitro investigated in order to mimic a possible subcutaneous administration of MAD. It was found that MAD constituted of monoolein/poloxamer and monoolein/poloxamer/sodium cholate mixtures were able to sustain CR release.MAD viscous vehicles were produced by xanthan gum.CR percutaneous absorption has been studied in vitro using excised human skin membranes [stratum corneum epidermis (SCE)] mounted into Franz cells. It was found that fluxes (F_n) of CR incorporated in MAD are influenced by the presence of monoolein based nanosystems. In particular xanthan gum based MAD better control CR diffusion from MAD.     

Development of suspending agent from sodium carboxymethyl mungbean starches

Three sodium carboxymethyl mungbean starches (SCMMSs) were selected, based on the physicochemical profiles and evaluated as potential pharmaceutical suspending agent in comparison with a sodium carboxymethyl tapioca starch and other five commercial suspending agents. Ibuprofen suspension was employed as a model formulation with 0.5, 1.0, and 2.0% w/v of suspending agents. Evaluation parameters included the determination of sedimentation volume ratio, redispersibility, viscosity and rheological properties and content uniformity studies. The results revealed that a high-viscosity modified mungbean starch, MMS-M-04, possessed suitable properties as a suspending agent and, at 1% concentration, was as effective as sodium carboxymethylcellulose and xanthan gum, two most-commonly used suspending agents. This modified starch could be further developed and employed as a new commercial suspending agent in the pharmaceutical industry.     

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.     

Development of Suspending Agent from Sodium Carboxymethyl Mungbean Starches

ABSTRACT

Three sodium carboxymethyl mungbean starches (SCMMSs) were selected, based on the physicochemical profiles and evaluated as potential pharmaceutical suspending agent in comparison with a sodium carboxymethyl tapioca starch and other five commercial suspending agents. Ibuprofen suspension was employed as a model formulation with 0.5, 1.0, and 2.0% w/v of suspending agents. Evaluation parameters included the determination of sedimentation volume ratio, redispersibility, viscosity and rheological properties and content uniformity studies. The results revealed that a high-viscosity modified mungbean starch, MMS-M-04, possessed suitable properties as a suspending agent and, at 1% concentration, was as effective as sodium carboxymethylcellulose and xanthan gum, two most-commonly used suspending agents. This modified starch could be further developed and employed as a new commercial suspending agent in the pharmaceutical industry.