ENHANCED DELIVERY THROUGH MODIFIED XANTHAN GUM IN SOLID DISPERSIONS

The aim of this investigation was to improve the dissolution properties of the water-insoluble drug ezetimibe (EZE) and potentially improve bioavailability. A combination of melt and adsorption techniques was employed for the preparation of solid dispersions. PEG 4000, PEG 6000, and Gelucire 44/14 were used as hydrophilic carriers, and lactose monohydrate was used as an adsorbent. Phase solubility curves are of AL type, indicating a linear relationship between drug solubility and carrier concentration. Dissolution studies reveal an improvement of in vitro drug release. Mathematical modeling indicates that drug release data are best described by the Korsmeyer–Peppas model, with Fickian diffusion as the possible drug-release mechanism. Physicochemical characterization of solid dispersions by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) suggests a reduction in drug crystallinity following dissolution enhancement. Hence, the present investigation reveals that the dissolution characteristics of EZE could be ameliorated in a solid dispersion. INTRODUCTION Out of several methods employed to enhance the dissolution characteristics of poorly water-soluble drugs, solid dispersion techniques have been widely reported by various researchers with encouraging results for different drugs. However, a solid dispersion system is somewhat limited by poor flow properties and poor stability. The processing variables of solid dispersions can be improved by the addition of adsorbent in the solid dispersion melt, thereby increasing the effective surface area of the drug leading to improved dissolution (1, 2). Various carriers have been used to prepare solid dispersion systems; among those, polyethylene glycols (PEG) and Gelucire 44/14 are employed in the present investigation. PEGs are used because of their low toxicity, high water solubility, low cost, and availability in a wide range of molecular weights. Gelucire 44/14 is a mixture of glycerol and PEG 1500 esters of long-chain fatty acids. The suffixes 44 and 14 refer to its melting point and its hydrophilic/lipophilic balance (HLB), respectively. PEG 4000, PEG 6000, and Gelucire 44/14 have been used successfully to improve the dissolution properties of poorly water-soluble drugs by preparing solid-dispersion systems (3–5). However, the solid dispersions prepared with these carriers are sticky and difficult to handle. Hence, they must be used in amalgamation with an adsorbent to improve their flow properties. Ezetimibe (EZE), 1-(4–fluorophenyl) –3(R)-[3-(4–fluorophenyl) –3(S) hydroxy-propyl]-4(S)-(4-hydroxyphenyl)-2azetidinone, is the first lipid-lowering drug that inhibits the intestinal uptake of cholesterol without affecting the absorption of fat-soluble nutrients. It is indicated as a monotherapy or in combination with statins for the treatment of hypercholesterolemia (6). EZE, being practically insoluble in water, exhibits a low dissolution profile in gastrointestinal fluids with variable bioavailability. Thus, researchers have investigated different approaches to ameliorate the dissolution characteristics of EZE (7–9) and optimize bioavailability with a less variable pharmacokinetic profile. In the present investigation, an attempt was made to improve the dissolution properties of EZE by preparing free-flowing solid dispersions. A combination of solid dispersion and adsorption techniques was employed for the preparation of the solid systems, using lactose monohydrate as adsorbent. The prepared solid dispersions were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). MATERIALS AND METHODS Materials EZE was kindly gifted by Mepro Pharmaceuticals Ltd. (Surendranagar, India). Gelucire 44/14 was a generous gift sample from Gattefosse Pvt. Ltd. (Mumbai, India). PEG 4000 and PEG 6000 were purchased from Sisco Research Lab Pvt. Ltd. (Mumbai, India). All reagents were of analytical grade. Double-distilled water was used throughout the work. Methods Phase Solubility Phase solubility studies were carried out as described by Higuchi and Connors (10). A quantity of EZE (about 10 mg) that exceeded its solubility was added to flasks containing 25 mL of solutions of different polymer *Corresponding author. diss-18-03-07.indd 55 8/31/2011 3:26:40 PM dx.doi.org/10.14227/DT180311P55

The present work aims at fabricating the colon specific drug delivery of mesalamine (MES) by modified pulsincap technique and using natural polysaccharides. Mesalamine being poorly water soluble drug, solubility has been increased by solid dispersion technique using natural polymers such as guar gum (GG), hupu gum (HG) and xanthan gum (XG). Solid dispersions were prepared by kneading method at 1:1, 1:2 and 1:3 weight ratios (drug:polymer). The solid dispersions were characterized by FTIR, DSC studies and evaluated for practical yield, drug content. Saturation solubility, pH dependent solubility, phase solubility studies and dissolution studies were carried out. The solubility of the formulated solid dispersions was high when compared to pure drug. The order of drug release from the solid dispersions prepared by different gums are as follows GG>HG>XG and different ratio exhibited release as 1:3>1:2>1:1. The optimized solid dispersions have been exploited in the formulation of pulsincaps. Bodies were made insoluble by formaldehyde treatment. Solid dispersions of mesalamine were filled in the bodies. Guar gum (GG) was used as hydrogel plug. Sealing of body and cap was done using ethyl cellulose. Ethyl cellulose coating was employed on pulsincaps to ensure the capsule empties from the stomach intact. The pulsincaps were assessed for their dissolution profiles. Percent MES release from pulsincaps prepared with pure MES, MES-GG, MES-HG and MES-XG solid dispersions were found to be 63.22, 96.25, 94.90 and 93.05 respectively. Our studies have shown very effective and desirable mesalamine release profiles by pulsincap formulations at simulated colon pH condition, which can enable the drug delivery specifically at colon segment.

The main objective of the present investigation to develop and evaluate solid dispersions of BCS Class II drugs etoricoxib employing various natural polymers, compatible with conventional manufacturing method to enhance solubility of poorly soluble drugs. In this study, etoricoxib solid dispersion were prepared using xanthan gum, gaur gum and acacia and their combinations by solvent evaporation method. Solid dispersions and pure etoricoxib in the form of powder were characterized in comparison with pure drug and corresponding physical mixtures in the same ratios by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffractogram, and in vitro drug release. Solid dispersion (ET11) prepared with 1: 2: 2: 2 drug carrier ratios were showed highest solubility in different solvents. Hence the solid dispersion (ET11) of 1: 2: 2: 2 ratios were selected for characterization. The DSC study indicated that the crystalline nature of etoricoxib was reduced to amorphous. The diffraction pattern of the solid dispersions in each figure indicates that diffraction peaks at 2ɵ values has less intensity than that of pure drugs. This indicated that the crystalline nature of drug sample was converted to amorphous with ET11. Scanning electron microscope photographs of solid dispersion seem to be more porous in nature. From the in vitro drug release profile, it can be seen that formulation ETM11 shows higher dissolution rate i.e. 98.2±1.3% compared with other formulations. It is predicted that, increasing concentration of carrier, increases the drug dissolution rate. This study has shown that the solid dispersion of etoricoxib using natural carrier can be promising formulation for solubility and dissolution enhancement. Natural polymers used have shown promising results in the modification of drug release from the formulations.

The aim of this study was to develop solid dispersions (SDs) of clarithromycin (CLA) using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and xanthan gum (XNG) as drug carriers. An in vitro dissolution study was performed in dissolution media of pH 6.8, and the results were compared with those of standard drugs. In vivo pharmacokinetic studies were carried out on an animal model (rabbits). The thermal behavior of each SD formulation was studied using differential scanning calorimetry analysis. It was concluded from the results that the crystalline nature of CLA had been transformed into an amorphous form in SDs. Pharmacokinetic parameters were observed to improve in HPMC- as well as XNG-based SDs compared with those of the standard drug. Additionally, powder X-ray diffraction analysis also confirmed the phase transition (crystalline to amorphous) of the drug present in SDs. Higher values of C max were found in the case of HPMC-based SDs, whereas t max values were prolonged in SDs based on XNG. Additionally, the enhanced half-life values indicated that SDs would have the potential to achieve a once-daily dose and improved patient compliance of drugs. Hence, the formulated SDs of a poorly soluble drug, based on HPMC and XNG as carriers, exhibited a more hydrophilic nature with enhanced aqueous solubility and therefore improved bioavailability compared with that of a standard drug.

Improving the solubility of drugs that are poorly soluble in water is a significant difficulty in pharmaceutical formulation development. To improve the solubility and rate of dissolution of pharmaceuticals, a commonly used technique called solid dispersion involves dispersing the drugs inside a hydrophilic carrier matrix. Because of their excellent environmental properties, affordability, and biocompatibility, natural gums derived from plants have garnered a lot of attention as flexible carriers in solid dispersion formulations. Natural gums that are hydrophilic and able to create films include guar gum, xanthan gum, and gum Arabic. These properties increase the surface area and improve the dissolution kinetics of the polymeric matrix by aiding in the dispersion of drug molecules throughout it. Recent advancements in the subject are also covered in the abstract, such as the use of natural gums in conjunction with specific other materials to increase the solubility and bioavailability of pharmaceuticals. Two cooperative processing methods that have showed promise in enhancing formulation stability and obtaining superior drug solubility characteristics are co-precipitation and hot melt extrusion. In order to increase the solubility of medications with limited water solubility, the current study explores the possible use of natural gums in solid dispersion systems. The paper's first part looks into solid dispersion and discusses the role that natural gums play in making medications more soluble. Moreover, improved treatment outcomes and higher patient adherence may result from the application of cutting-edge technologies and techniques meant to boost pharmaceutical solubility.

Introduction. Flavonoids, despite their pronounced therapeutic benefits, are limitedly used in medicine as active pharmaceutical ingredients (API) owing to a complex of unsatisfactory physicochemical properties. In order to study the mentioned problem, we decided to use quercetin as model compound with extremely low water solubility and dissolution in gastrointestinal (GI) tract media. Therefore, the main idea appears to study the possibility and prospects of hot melt extrusion (HME) application for enhancement the solubility properties of quercetin in the composition of solid dispersion system (SDS) based on hydrophilic polymeric carrier (polyvinylpyrrolidone vinyl acetate, PVP/VA). Consequently, there is a necessity to select effective drug-to-polymer ratio in solid dispersion for providing better solubility and dissolution properties.Aim. Assessment of PVP/VA effect on quercetin solubility properties in binary solid dispersion prepared by HME.Materials and methods. Quercetin substance with purity 98 % was purchased from Molekula Limited, United Kingdom. PVP/VA (copolymer of polyvinylpyrrolidone with vinyl acetate in the ratio of 60 : 40, VIVAPHARM® PVP/VA 64) as carrier was procured from JRS PHARMA (JRS PHARMA GmbH & Co. KG, Germany). Quercetin SDS were prepared using micro-conical twin screw compounder HAAKE™ MiniCTW (Thermo Fisher Scientific, Germany). The obtained samples were analyzed by phase-contrast microscopy, FTIR spectroscopy and differential scanning calorimetry (DSC). Quercetin quantitative content in SDS were determined by UV-spectrophotometry.Results and discussion. The improvement of water solubility and dissolution rates of quercetin SDS in comparison with pure substance was observed for all solid dispersion compositions irrespective to drug-to-polymer ratio. Notably, with reduction of quercetin content in SDS compositions the PVP/VA contribution was increased. We found partial or even complete amorphization of API in formulations with 1 % and 5 % quercetin content, resulting in the improvement of water solubility properties, stability of solutions and increased dissolution rates in GI tract media. Water solubility of 1 % SDS relative to pure substance was enhanced by 353-fold. At the same time, the complete release of quercetin from 1 % SDS was achieved in 40 minutes in the hydrochloric acid and citrate buffer, and also quercetin dissolution of 90 % in 60 minute was observed in phosphate buffer.Conclusion. 1 % quercetin SDS based on PVP/VA appears to be the most promising for solid dosage forms development.

Flocculation of food dispersions by gums: isotropic/anisotropic dispersion separation by xanthan gum

Chitosan, xanthan and locust bean gum matrices crosslinked with β-cyclodextrin as green sorbents of aromatic compounds

Objective: The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble drug by solid dispersion (SD) technique, in order to conduct an investigation of the effect of these natural hydrophilic polymers on release mechanism from SD.Methods: The SD of diazepam (DZM) were prepared by using modified sodium alginate (SA) and modified guar gum (GG) in different drug: polymer ratios (1:1 and 1:2) by using physical mixture method (PM) and fusion method (FM). Further, the formulations were characterized for calibration curve, Fourier transforms infrared spectroscopy (FTIR) studies, % age practical yield, drug content estimation, solubility studies, dissolution studies.Results: The pure drug and SD were characterized by pre and post-formulations studies. The %age practical yield ranged from 92.9±0.25 to 49±0.57%, and the drug content estimation ranged from 99.34±0.40 to 65.25±0.25 %. The FTIR studies shown that the compatibility between pure drug and natural polymers was stable. All the SD showed improved solubility as compared to the pure drug (PD). SD prepared with modified SA (1:2) by PM and FM shown the huge enhancement of solubility and dissolution rate of the DZM. This can be specific to the improvement in wettability and dispersibility, as well as enhances the drug amorphous fraction.Conclusion: On the basis of the research study, the SD technique shows the enhancement in the solubility of poorly water-soluble drug using natural polymers. SD containing natural polymers prepared with PM and FM shown the remarkable improvement in the release outline compared with PD, DZM.

Application of Enhanced oil recovery methods (EOR) in offshore oil fields are getting more popular with the advancement in technology and chemicals used. Polymer flooding is one of the most successful projects to improve water mobility by increasing the viscosity. Application of polymers promises to improve areal sweep efficiency and consequently recovery factor. However the main concern associated with injection of chemicals in offshore oil fields is the possibility of leakage and pollution of marine systems affecting biodiversity and environment. The following study focuses on rheological properties of three bio-polymers: Xanthan gum, Wulan gum and Potato starch in laboratory conditions as viscosifying agents. The study involved characterization of each polymer at different concentrations from 500 ppm to 5,000 ppm dosage. Sensitivity analysis on various reservoir temperatures were also performed from 25°C to 55°C to fit Kazakhstan reservoirs along with sea water salinity to simulate Kazakhstan reservoir conditions. Results from rheological studies showed that 3,000 ppm is considered as the optimum concentration from Xanthan and Wulan gums, Potato starch did not show any good results as viscosifying agent. Further temperature effect studies showed that both Xanthan and Wulan gums have a strong temperature resistance and does not experience dramatic viscosity drop at reservoir temperatures in a range of 8-14% of loss. However, salinity effect showed that Wulan gum tends to lose rheological properties in high salinity environment and high viscosity drop. Rheological studies showed that Xanthan gum is highly resistant to salinity and temperature changes, while Wulan is only temperature resistant. The obtained rheological data were correlated with the Ostwald–de Waele power-law model to characterize fluid flow parameters, shear thinning behavior and identify n, k values. The correlations affirmed the shear-thinning properties of Xanthan and Wulan gums, a critical attribute for effective oil displacement in offshore reservoirs Core flooding experiments were performed for each polymer at the optimum concentration, salinity and temperature. Carbonate cores were used to simulate reservoir conditions and assess the effectiveness of natural polymers in improving oil recovery. Core flooding experiments with Xanthan and Wulan gums showed incremental oil recovery of 30 and 20% respectively. In the context of Kazakhstan's Caspian Sea, these findings herald a promising future for enhanced oil recovery, leveraging the robustness of natural polymers in challenging offshore conditions. Overall, these polymers demonstrated impressive results in displacing oil under harsh offshore reservoir conditions

Carvedilol (CVD) is a non-selective β-blocker. CVD is included in BCS class II. It has low water solubility. In this research, solid dispersion was used to increase the solubility and dissolution profile of CVD. In silico study using the ligand-ligand docking method. The preparation of solid dispersion using the kneading method with a weight ratio of 1:1, 1:2, 1:3, and 1:4, evaluation of solid dispersion includes solubility and dissolution. The best solid dispersion was characterized using FTIR, DSC, and PXRD. In silico study showed complexes CVD-SA, CVD-GG, CVD-XG and CVD-LBG have a hydrogen interaction. SA and XG were chosen as carriers in solid dispersion. CVD solid dispersion showed increased solubility in all samples, with the highest increase at 90.63 times at CVD: XG (1:4). The results of the dissolution profile obtained at 60 min are 64.95 ± 0.45% at pure CVD, 83.32 ± 1.19% at CVD:SA (1:4), and 72.56 ± 3.62% at CVD: XG (1:4). The FTIR spectrum indicates an interaction between CVD and SA. The thermogram indicated the amorphous drug, and the diffractogram showed a decrease in crystallinity. Solid dispersion is proven to increase the solubility and dissolution profile of CVD. Solid dispersion CVD: SA (1:4) showed the highest solubility and dissolution profile.

Solid dispersions formulated to improve solubility & dissolution rate of poorly soluble drug clopidogrel bisulfate. Physical mixtures & solid dispersions of clopidogrel bisulfate were prepared with carboxymethylcellulose sodium and xanthan gum in the weight ratios of 1:1, 1:3 and 1:5 using kneading method. The prepared solid dispersions were characterized by solubility determination, drug content, In Vitro dissolution and accelerated stability studies. The results revealed that solid dispersions shown improvement in solubility and dissolution characteristics than the physical mixtures and pure drug. The reasons for increase in solubility and dissolution rate is decrease in particle size, increased surface area, amorphous state of the drug in solid dispersions, absence of aggregation and increased wetting of drug molecules. It was also observed that solid dispersions of drug with both carriers showed increased dissolution rate in the ratio of 1:5 (Drug: Carrier) in comparison to pure drug and found to be stable during stability studies.

This recent research work was aimed to develop the oral dissolving films of gliclazide. Solid dispersions of gliclazide using natural polymers such as hupu gum (HG), guar gum (GG) and xanthan gum (XG) were prepared by kneading technique and the optimized solid dispersion was exploited to develop the gliclazide films. Different grades of HPMC (E5, 50 cps and K4M) were used to develop the films by adapting solvent casting method. Six formulations (FG1-FG6) of gliclazide films were prepared. The films were evaluated for their thickness, tensile strength, elongation, weight variation, folding endurance, drug content uniformity and surface pH and obtained satisfactory results. The films were assessed for their compatibility between the drug and excipients by FTIR and DSC techniques. The film formulations were subjected to disintegration, in vitro drug release and pharmacodynamic studies. From the results FG4 formulation was found as best formulation which contains HPMC K4M and gliclazide solid dispersion with guar gum at weight ratio of 1:2. The formulation had showed excellent film characteristics such as disintegration time of 64 sec and drug release was 97.30 % within 10 min. The optimized film formulation (FG4) showed excellent stability over 45 days when stored at 40°C /60% RH. The pharmacodynamic study in animal models (rats) proved that fast dissolving films of gliclazide produced a faster onset of action compared to that of conventional formulation. Keywords: Blood glucose levels, elongation, folding endurance, solvent casting, tensile strength, wistar rats.


 This research work was aimed to develop the telmisartan fast dissolving films. Fast dissolving films allow rapid drug dissolution in the oral cavity and thereby bypass the first pass metabolism. Solid dispersions of telmisartan using natural polymers such as hupu gum (HG), guar gum (GG) and xanthan gum (XG) were prepared by kneading technique and the optimized solid dispersion was exploited in the development of rapidly dissolving film. Telmisartan films were prepared by solvent casting method using different grades of HPMC (E5, 50 cps and K4M). Six formulations (FT1-FT6) of telmisartan films were prepared and evaluated for their physical characteristics such as thickness, tensile strength, percentage elongation, weight variation, folding endurance, drug content uniformity and surface pH and gave satisfactory results. The compatibility of the drug in the formulation was confirmed by FTIR and DSC studies. The formulations were subjected to disintegration, in vitro drug release and pharmacodynamic studies on spontaneous hypertensive rats (SHR). Amongst the formulations of FT1-FT6, FT6 was found as best formulation which contains HPMC E5 and telmisartan solid dispersion with guar gum at weight ratio of 1:2 and showed excellent film forming characteristics such as disintegration time at 42 sec and percentage drug release 97.98% within 10 minutes. The optimized film formulation (FT6) showed excellent stability over 45 days when stored at 40°C/60% RH. The pharmacodynamic study in SHR proved that fast dissolving films of telmisartan produced a faster onset of action.

This study explores the enhancement of oral bioavailability, dissolution rate, and solubility of weakly water-soluble fluoroquinolone antibiotic, ofloxacin (OFL), by solid dispersion (SD) formulation prepared using the spray drying technique. Hydrophilic polymers; hydroxypropyl methylcellulose (HPMC) and xanthan gum (XNG) were used as carriers. FT-IR spectroscopy indicated hydrogen bonding between OFL and the polymer's backbone. DSC and PXRD analyses revealed a transformation from the crystalline to the amorphous state. SEM images revealed reduced particle size and changed surface morphology, which are favorable for solubility improvement. The in vitro drug release studies, performed in simulated gastric conditions (pH 6.8) showed a significant improvement in the drug release, 97.88% and 82.34% for HPMC-based (O–H) and XNG-based (O–X) SDs, respectively, as compared to only 59.2% for unprocessed OFL. Further, in vivo, kinetics reported in a validated HPLC-UV method in rabbits showed an impressive Cmax (O–H: 4.33 µg mL−1; O–X: 4.12 µg mL−1; OFL: 1.8 µg mL−1) and prolonged t1/2 (8 h vs. 5 h). Thus demonstrating a significant enhancement in bioavailability in the rabbit model. The SDs produced with HPMC and XNG represent a promising strategy to improve the solubility and in vivo performance of OFL, which may translate to improved therapeutic efficacy.