The effect of phase viscosity ratio on the rheology of liquid two phase gelatin-locust bean gum systems

The rheological behaviour of liquid two phase gelatin–locust bean gum (LBG) systems, comprising of (a) liquid LBG enriched continuous phase, and (b) flow-deformable gelatin-enriched dispersed particles seems to be determined, at the same phase composition, by phase viscosity ratio (μ). In the μ range from 0.03 to 0.21, viscosity dropped to values noticeably lower (13–40 times) than those of the corresponding LBG solution. Decrease in the viscosity of the mixtures was not observed at μ=0.5–0.6, corresponding that to the maximum energy scatter inside the droplets, in agreement with Mason’s conception of droplet deformation and disruption of liquid Newtonian emulsions.     

Gelling interactions of phycocolloids extracted from red algae with a galactomannan from locust bean and a glucomannan from konjac tuber

The synergistic interaction between three red algae extracts and the galactomannan from locust bean (Ceratonia siliqua L.) and the glucomannan from the konjac tuber (Amorphophallus konjac C. Koch (syn.A. rivieri Durien var. konjac (C. Kock) Engler)) has been characterized in terms of gel properties. The extract obtained fromEucheuma alvarezii Doty (E. cottonii of commerce) was highly synergistic with bothkonjac flour and locust bean gum.Furcellaria fastigiata (Huds.) Lamour andEucheuma gelatinae (Esper) extracts were only slightly synergistic with locust bean gum, but were found to be highly synergistic with konjac flour.     

The effect of degradation on κ-carrageenan/locust bean gum/konjac glucomannan gels at acidic pH

The feasibility of textural and rheological modification of gels containing κ-carrageenan (KC) and locust bean gum (LBG) by addition of konjac glucomannan (KGM) was investigated. Special attention was paid to the effect of polysaccharide degradation during heating at acidic pH. The general effect of polysaccharide degradation was to decrease the Young's modulus, while the fracture strain in extension was scarcely affected unless the degradation was very severe.     

Binding of mineral elements to locust bean gum influences availability in vitro

Experiments were conducted to evaluate the extent to which element binding of locust bean gum (LBG) affects the availability of calcium, iron, and zinc in the gut. Infant formula was supplemented with increasing amounts of LBG and subjected to an intraluminal digestion procedure. Element binding was measured by eliminating the complexes by twofold centrifugation. Availability of the elements was determined using a validated continuous-flow dialysis technique. Elemental content of the samples, supernatants, and dialysates was analyzed with validated atomic absorption spectrometry. LBG provided small amounts of intrinsic calcium (1.13 ± 0.02 mg/g) and trace amounts of iron (0.02 ± 0.00 mg/g) and zinc (0.01 ± 0.00 mg/g), which were strongly bound to the LBG molecule (respectively: 76.6 ± 3.3%, 83.4 ± 1.2%, 96.7 ± 6.6%). Correlation analysis, between percent element bound by LBG after centrifugation and percent trapped after dialysis, yielded significant correlation only for the data of zinc (r=0.93). For calcium and iron, no correlation could be demonstrated; however, for iron a similar trend was observed. These findings suggest that element binding of LBG has a major influence on the availability of zinc and maybe of iron. For calcium, other factors might also be involved, affecting availability.     

Studies on κ-carrageenan/locust bean gum mixtures in the presence of sodium chloride and sodium iodide

The solution properties of κ-carrageenan and κ-carrageenan/locust bean gum mixtures have been studied by small deformation oscillation measurements and differential scanning calorimetry (DSC) in the presence of sodium chloride and sodium iodide. Both salts induced the κ-carrageenan to undergo a coil-helix conformational change as noted by an increase in the storage and loss moduli (G′, G′) and by an exothermic peak in the DSC cooling curves. The enthalpy ΔH_c-h and temperature of the conformational transition T_c-h were higher in Nal compared to NaCl and T_c-h increased with increasing the concentration of both electrolytes. Gelation was not observed for carrageenan or carrageenan/locust bean gum mixtures in the presence of up to 200 mM Nal. Although carrageenan alone did not gel in the presence of 100 mM NaCl, a weak gel was obtained for a mixture containing 0.9%/0.1% carrageenan/locust bean gum. Furthermore, the mixture showed hysteresis in both the rheological and DSC cooling and heating curves. A strong gel was produced for carrageenan alone in the presence of 200 mM NaCl and the gel strength increased on adding a small proportion of locust bean gum (0.9%/0.1%). © 1997 John Wiley & Sons, Inc. Biopoly 41: 657–671, 1997     

Rheology and synergy of κ-carrageenan/locust bean gum/konjac glucomannan gels

The rheology and melting of mixed polysaccharide gels containing konjac glucomannan (KGM), locust bean gum (LBG) and κ-carrageenan (KC) were studied. Synergy-type peaks in the Young's modulus at optimal mixing ratios were found for both KC/LBG and KC/KGM binary gels at a fixed total polysaccharide content (1:5.5 for LBG:KC and 1:7 for KGM:KC). The Young's modulus peak for KC/KGM was higher than for KC/LBG gels. The same stoichiometric mixing ratios were found when either LBG or KGM was added to KC at a fixed KC concentration, where the Young's modulus increased up to additions at the stoichiometric ratio, but leveled off at higher LBG or KGM additions. Addition of KGM or LBG to the 2-component gels beyond the stoichiometric (optimal) mixing ratio at a fixed total polysaccharide content led to a decrease in the Young's modulus and an increase in the rupture strain and stress in extension, and both trends were stronger for KGM than for LBG.     

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25°C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (λ_max), respectively. Solubility of atorvastatin calcium (from 100 to 345 μg/ml), cefuroxime axetil (from 441 to 1948 μg/ml), clotrimazole (from 63 to 677 μg/ml), ketoconazole (from 16 to 500 μg/ml), and metronidazole benzoate (from 112 to 208 μg/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs.KEY WORDS: dissolution, effervescence, fusion, solid dispersion, solubility     

Phase separation in dextran/locust bean gum mixtures

Dextran/locust bean gum (LBG) mixtures have been prepared and investigated with respect to their phase separation behaviour. These systems exhibited phase separation at 20 °C, the upper phase, itself biphasic, being enriched with locust bean gum but also containing dextran, whereas the lower phase contained only dextran. This lower phase was a liquid. The upper phase, which did not flow, was characterized by means of rheological dynamic measurements. Clearly, its behaviour was typical of a gel, the three-dimensional structure of which can be ascribed to self-association of LBG chains owing to the very high concentration of the galactomannan in this upper phase. The self-association of the galactomannan was confirmed by fluorescence microscopy carried out on mixtures containing fluorescein isothiocyanate (FITC)-labelled dextran. The rheological behaviour of a concentrated LBG solution was also investigated as a function of time, clearly showing progressive formation of a weak gel structure.     

Enhancement of dissolution profile by solid dispersion (kneading) technique

This article investigates enhancement of the dissolution profile of valdecoxib using solid dispersion with PVP. The article also describes the preparation of fast-dissolving tablets of valdecoxib by using a high amount of superdisintegrants. A phase solubility method was used to evaluate the effect of various water-soluble polymers on aqueous solubility of valdecoxib. Polyvinyl pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the method of kneading. Dissolution studies, using the USP paddle method were performed for solid dispersions of valdecoxib. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffractometry (XRD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Tablets were formulated containing solid dispersion products and compared with commercial products. IR spectroscopy, XRD, and DSC showed no change in the crystal structure of valdecoxib. Dissolution of valdecoxib improved significantly in solid dispersion products (<85% in 5 minutes). Tablets containing solid dispersion exhibited better dissolution profile than commercial tablets. Thus, the solid dispersion technique can be successfully used for improvement of dissolution of valdecoxib. Published: August 18, 2006     

A Menthol-Based Solid Dispersion Technique for Enhanced Solubility and Dissolution of Sulfamethoxazole from an Oral Tablet Matrix

A menthol-based solid dispersion was designed to improve the intrinsic solubility of the poorly soluble sulfamethoxazole- a class II drug molecule of Biopharmaceutics Classification System (BCS) displaying widespread antibacterial activity. Solid dispersions of menthol and sulfamethoxazole were compressed with hydroxypropyl methylcellulose (HPMC) into suitable sulfamethoxazole-loaded matrix tablets for oral drug delivery. The sulfamethoxazole-loaded solid dispersions and compressed tablets were characterized for their physicochemical and physicomechanical properties such as changes in crystallinity, melting point, molecular transitions, and textural analysis for critical analysis of their effects on the solubility and dissolution of sulfamethoxazole. The formulations were further evaluated for swelling, degradation, solubility, and in vitro drug release behavior. In vitro drug release from the sulfamethoxazole-loaded matrix tablets displayed a minimum and maximum fractional release of 0.714 and 0.970, respectively. The tablets further displayed different release rate profiles over the study periods of 12, 16, 48, and 56 h which were attributed to the varying concentrations of menthol within each formulation. Menthol was determined as a suitable hydrophilic carrier for sulfamethoxazole since it functioned as a solubilizing and release-retarding agent for improving the solubility and dissolution of sulfamethoxazole as well as controlling the rate at which it was released.KEY WORDS: crystallinity, menthol, oral solubility and dissolution, solid dispersion, sulfamethoxazole     

Improved Hypolipidemic Effects of Xanthan Gum-Galactomannan Mixtures in Rats

This study describes the effects of mixtures of xanthan gum and galactomannan, guar gum, or locust bean gum, on the lipids in plasma and liver in non-diabetic and diabetic rats. Non-diabetic rats were fed cholesterol-free diets with 3% guar gum, locust bean gum, or xanthan gum (3G, 3L, and 3X), or a mixture of xanthan gum and guar gum or locust bean gum (1:2, w/w) (2G1X, 2L1X) for 2 weeks. Rats fed diets not containing these polysaccharides were used as controls. The total cholesterol in plasma and the triacylglycerol in liver were significantly lowered in rats fed the 2G1X diet. The 3G, 3X, 3L, and 2L1X diets showed no significant effect on the total cholesterol and triacylglycerol in plasma and liver. In the streptozotocin-induced (STZ) diabetic rats, the total cholesterol in plasma was lowered in rats fed the 3G, 3X or 2G1X diet for 4 weeks, and the 2G1X diet was more effective than the 3G and 3X diets. The triacylglycerol in plasma in STZ diabetic rats was also significantly lowered by the 2G1X diet. These results showed that a mixture of xanthan gum and guar gum has an improved hypolipidemic effect on non-diabetic and STZ diabetic rats. The effects of the 2G1X diet on the diabetic symptoms in STZ diabetic rats, suppression of food and water intakes, decrease in glucose in urine, and lowering of plasma glucose, were also observed.     

Process optimization and characterization of poloxamer solid dispersions of a poorly water-soluble drug

The objective of the present investigation was to improve the dissolution rate of Rofecoxib (RXB), a poorly water-soluble drug by solid dispersion technique using a water-soluble carrier, Poloxamer 188 (PXM). The melting method was used to prepare solid dispersions. A 3² full factorial design approach was used for optimization wherein the temperature to which the melt-drug mixture cooled (X ₁) and the drug-to-polymer ratio (X ₂) were selected as independent variables and the time required for 90% drug dissolution (t₉₀) was selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution of RXB from PXM solid dispersions, a low level ofX ₁ and a high level ofX ₂ were suitable. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution of RXB from solid dispersion might be due to a decrease in the crystallinity of RXB and PXM and dissolution of RXB in molten PXM during solid dispersion preparation. In conclusion, dissolution enhancement of RXB was obtained by preparing its solid dispersions in PXM using melting technique. The use of a factorial design approach helped in identifying the critical factors in the preparation and formulation of solid dispersion. Published: April 13, 2007     

A celluloytic complex from <Emphasis Type="Italic">Clostridium cellulovorans</Emphasis> consisting of mannanase B and endoglucanase E has synergistic effects on galactomannan degradation

In our previous study using a fluorescently labeled cohesin biomarker, we detected and identified a putative cellulosomal mannanase belonging to the glycosyl hydrolase family 26 from Clostridium cellulovorans in xylan-containing cultures. In this study, a mannanase gene, manB from C. cellulovorans, was expressed in Escherichia coli. The optimal pH of a purified enzyme was around pH 7.0 and the optimal temperature was 40°C. The purified mannanase B (ManB) showed high hydrolytic activity toward galactomannan. An assembly of ManB with mini-CbpA, which contains a carbohydrate-binding module that provides proximity to insoluble substrates, increased the activity toward galactomannan [locust bean gum (LBG) and guar gum] 1.7- and 2.0-fold over those without mini-CbpA. We tested the synergistic effects on galactomannan (LBG and guar gum) degradation using cellulosomal mannanase ManB with cellulosomal endoglucanase E, which was predicted to have mannanase activity in C. cellulovorans as a cellulolytic complex. When assembled with the mini-CbpA, the mixture of endoglucanase E (EngE) and ManB at a molar ratio of 1:2 showed the highest synergistic effect (2.4-fold) on LBG. The mixture at a ratio of 1:3 showed the highest synergistic effect (2.8-fold) on guar gum. These synergistic actions indicated that ManB assembled with mini-CbpA hydrolyzed insoluble galactomannan, which in turn promoted soluble galactomannan degradation by EngE.     

Evaluation of Drug Load and Polymer by Using a 96-Well Plate Vacuum Dry System for Amorphous Solid Dispersion Drug Delivery

It is well recognized that poor dissolution rate and solubility of drug candidates are key limiting factors for oral bioavailability. While numerous technologies have been developed to enhance solubility of the drug candidates, poor water solubility continuously remains a challenge for drug delivery. Among those technologies, amorphous solid dispersions (SD) have been successfully employed to enhance both dissolution rate and solubility of poorly water-soluble drugs. This research reports a high-throughput screening technology developed by utilizing a 96-well plate system to identify optimal drug load and polymer using a solvent casting approach. A minimal amount of drug was required to evaluate optimal drug load in three different polymers with respect to solubility improvement and solid-state stability of the amorphous drug-polymer system. Validation of this method was demonstrated with three marketed drugs as well as with one internal compound. Scale up of the internal compound SD by spray drying further confirmed the validity of this method, and its quality was comparable to a larger scale process. Here, we demonstrate that our system is highly efficient, cost-effective, and robust to evaluate the feasibility of spray drying technology to produce amorphous solid dispersions.     

Thermal, Mechanical, and Molecular Relaxation Properties of Frozen Sucrose and Fructose Solutions Containing Hydrocolloids

Model frozen systems formulated with 20wt% sucrose or fructose and with the addition of 0.3 or 0.5wt% of xanthan gum (XG), guar gum (GG), locust bean gum (LBG), or a 50wt% mixture of XG and LBG were studied by differential scanning calorimetry, dynamic mechanical analysis, and ¹H-pulsed nuclear magnetic resonance. Melting onset of either the sucrose or fructose model systems was not affected by the addition of hydrocolloids. As expected, ice content was lower in fructose than in sucrose systems. Addition of hydrocolloids had no effect on ice content, except when the blend of XG and LBG was added to the fructose system, where ice content was significantly diminished. Hydrocolloids decreased molecular mobility for both frozen sucrose or fructose solutions, especially for the addition of XG/LBG blend. Relaxation times and storage modulus of the frozen systems with added hydrocolloids were significantly lower than the control frozen sugar solutions.     

In vivo evaluation of modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug,nimodipine

This work examines the influence of modified gum karaya (MGK) on the oral bioavailability of a poorly water-soluble drug, nimodipine (NM), in comparison with that of gum karaya (GK). A cogrinding method was selected to prepare mixtures of NM and GK or MGK in a 1:9 ratio (NM:GK/MGK). Differential scanning calorimetry (DSC), Fourier transmission infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solubility studies, and in vitro release studies were performed to characterize the properties of the cogrinding mixtures. No drug-carrier interactions were found, as confirmed by DSC and FT-IR studies. The XRD study revealed that the crystallinity of NM was identical in both the cogrinding mixtures and was decreased when compared to that of physical mixtures or pure NM. The in vitro release rate of NM from both cogrinding mixtures was significantly higher than that of physical mixtures or pure NM. The in vivo study revealed that the bioavailability of NM from pure drug was significantly lower when compared to the cogrinding mixtures. The oral bioavailability was found to be NM powder < cogrinding mixtures of NM and GK < cogrinding mixtures of NM and MGK < NM solution. It can be inferred from the above results that MGK, an economical carrier, could be used for the dissolution enhancement of NM.     

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.     

Acyclovir-Polyethylene Glycol 6000 Binary Dispersions: Mechanistic Insights

The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.     

Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hotstage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions suggests the transformation of crystalline etoricoxib into an amorphous form. In the HSM examination of solid dispersions, the dissolution of drug in the lipid carriers was observed, which was also confirmed by the absence of etoricoxib peak in DSC curves of solid dispersions. The DRIFTS spectra revealed the presence of hydrogen bonding in solid dispersions. The in vitro dissolution rate of solid dispersions as compared with pure etoricoxib, spray-dried etoricoxib, and physical mixtures of drug with lipid carriers. Therefore, the dissolution rate of poorly water-soluble drug etoricoxib can be significantly enhanced by the preparation of solid dispersions using lipid carriers by spray drying technique. Published: October 19, 2005     

A Co-blended Locust Bean Gum and Polymethacrylate-NaCMC Matrix to Achieve Zero-Order Release via Hydro-Erosive Modulation

Locust bean gum (LBG) was blended with a cellulose/methacrylate-based interpolyelectrolyte complex (IPEC) to assess the hydro-erosive influence of addition of a polysaccharide on the disposition and drug delivery properties inherent to IPEC matrix. The addition of LBG modulated the drug (levodopa) release characteristics of the IPEC by reducing excessive swelling and preventing bulk erosion. After 8 h in pH 4.5 dissolution medium, gravimetric analysis established that IPEC tablet matrix eroded by 30% of the initial weight due to bulk erosion while LBG-blended IPEC (LBG-b-IPEC) demonstrated surface erosion accounting to 62% of initial weight (596→226.8 mg). Mathematical modeling of the drug release data depicted a transformation from non-Fickian mechanism (IPEC matrices) to zero-order drug release pattern (LBG-b-IPEC matrices) with the linearity of release profile being close to 1 (R² = 0.99). Physicochemical characterizations employing Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) explicated that LBG interacted with IPEC by its hydrophilic groups associating with the existing water-holding bodies of IPEC to produce compact matrices. The lattice atomistic modeling elucidated that LBG acted as a linker with the formation of intra- and intermolecular hydrogen bonds generating a highly stabilized polysaccharide-polyelectrolytic structure which influenced the improved properties observed.KEY WORDS: controlled release, interpolyelectrolyte complex, levodopa, locust bean gum, oral drug delivery, swelling and erosion