Molecular Weight Methylcellulose Research Articles

Effect of different surface active polysaccharide derivatives on the formation of ethyl cellulose particles by the emulsion-solvent evaporation method

This paper aims at a better understanding of the systematic production of the ethyl cellulose (EC) particles by using an emulsification-solvent evaporation method in the presence of different polysaccharide derivatives. In particular, the role of different surface active polymers i.e. one ionic—carboxymethyl cellulose, one nonionic—hydroxyethyl cellulose, and two amphiphilic—high molecular weight methyl cellulose and low molecular weight methyl cellulose on EC particle formation was investigated. We have established how individual surface active polysaccharides with varying concentration from 0.1 to 3.0 wt% affect particle size and its distribution, particle shape, surface charge, and particle surface morphology. The interdependencies between surfactant nature and concentration at constant processing parameters and the subsequent nano- to micro-particle characteristics are discussed. It was determined that the particle size, surface morphology, supramolecular structure and surface properties of EC particles, prepared by an emulsion evaporation method can be effectively controlled by the type and concentration of used polysaccharide surfactant yielding spherical particles sizes from 170 nm to the micrometer level with smooth particle surfaces or remarkably a wrinkled surface morphology or “particle on particle” structures.Graphical abstract

Molecular Weight Dependence of Methylcellulose Fibrillar Networks

Gelation of aqueous methylcellulose (MC) solutions upon heating has been shown to result from the formation of a network of semiflexible fibrils, with diameters of 15 ± 2 nm. Here, we investigate the impact of MC molecular weight on the elasticity and structure of aqueous gels at concentrations between 0.1 and 3 wt %. Small-amplitude oscillatory shear measurements conducted at a fixed concentration reveal that the gel modulus increases monotonically by a factor of 5 for weight-average molecular weights (Mw) between 22 and 550 kg/mol. Small-angle X-ray scattering data, fit to a semiflexible cylinder model, demonstrate that the fibril radius, Kuhn length, and volume fraction are approximately constant throughout this molecular weight range. Small-angle light scattering shows that the fibrillar-rich and fibrillar-depleted domains within the gel are associated with an essentially invariant heterogeneity correlation length. Direct visualization by cryo-TEM reveals that lower molecular weight MC forms fibrils o...

Surfactant-free solubilization and systemic delivery of anti-cancer drug using low molecular weight methylcellulose

Docetaxel, an advanced taxoid, has been widely used as an anti-mitotic agent, but further augmentation of its properties is still required, including improvement in low aqueous solubility. Herein, we report the development of bio-eliminable low molecular weight methylcellulose-based surfactant-free injectable formulation for the delivery of docetaxel. Crude methylcellulose, a hydrophobically modified cellulose derivative, was hydrolyzed by an enzymatic degradation method to obtain low molecular weight methylcellulose (LMwMC). Docetaxel was successfully loaded in micelles with small particle sizes high drug loading and sustained release profile. The in vivo anti-cancer effects of intravenously injected nanoparticle systems in B16F10 melanoma xenograft mice were evaluated and demonstrated a significantly enhanced therapeutic effect with the docetaxel-LMwMC micellar aggregates compared to a commercially available docetaxel, Taxotere®. Surfactant-free solubilization of docetaxel could be a promising delivery method for effective insoluble drug delivery for anti-tumor efficacy.

Conformation of Methylcellulose as a Function of Poly(ethylene glycol) Graft Density.

Low molecular weight thiol-terminated poly(ethylene glycol) (PEG) (M ≈ 800) has been grafted onto a high molecular weight methylcellulose (MC, Mw ≈ 150000) by a facile thiol-ene click reaction; graft densities varied from 0.7% to 33% (grafts per anhydroglucose unit). Static and dynamic light scattering reveals that the overall radius of the chain increases systematically with graft density, in a manner in excellent agreement with theory. As the contour length remains unchanged, it is apparent that grafting leads to an increase in the persistence length of this semiflexible copolymer, by as much as a factor of 4. These results represent the first experimental verification of the excluded volume theory at low grafting densities, and demonstrate a promising synthetic platform for systematically increasing the persistence length of a model semiflexible, water-soluble polymer.

Size-exclusion chromatography of ultrahigh molecular weight methylcellulose ethers and hydroxypropyl methylcellulose ethers for reliable molecular weight distribution characterization

Size-exclusion chromatography (SEC) coupled with multi-angle laser light scattering (MALLS) and differential refractive index (DRI) detectors was employed for determination of the molecular weight distributions (MWD) of methylcellulose ethers (MC) and hydroxypropyl methylcellulose ethers (HPMC) having weight-average molecular weights (Mw) ranging from 20 to more than 1,000kg/mol. In comparison to previous work involving right-angle light scattering (RALS) and a viscometer for MWD characterization of MC and HPMC, MALLS yields more reliable molecular weight for materials having weight-average molecular weights (Mw) exceeding about 300kg/mol. A non-ideal SEC separation was observed for cellulose ethers with Mw>800kg/mol, and was manifested by upward divergence of logM vs. elution volume (EV) at larger elution volume at typical SEC flow rate such as 1.0mL/min. As such, the number-average molecular weight (Mn) determined for the sample was erroneously large and polydispersity (Mw/Mn) was erroneously small. This non-ideality resulting in the late elution of high molecular weight chains could be due to the elongation of polymer chains when experimental conditions yield Deborah numbers (De) exceeding 0.5. Non-idealities were eliminated when sufficiently low flow rates were used. Thus, using carefully selected experimental conditions, SEC coupled with MALLS and DRI can provide reliable MWD characterization of MC and HPMC covering the entire ranges of compositions and molecular weights of commercial interest.

Thermo-reversible injectable gel based on enzymatically-chopped low molecular weight methylcellulose for exenatide and FGF 21 delivery to treat types 1 and 2 diabetes

Diabetes is the fastest growing metabolic disease that fails to utilize glucose properly due to insulin deficiency or insulin resistance. Although several limited studies demonstrated non-invasive means of protein delivery, major hurdles for commercial success such as short half-life, enzymatic degradation and low bioavailability still remain to overcome. Methylcellulose (MC), a hydrophobically-modified cellulose derivative, forms temperature reversible gel in aqueous solution. However, as the gelling temperature of MC is higher than body temperature, it should be lowered to below body temperature for practical clinical application. In order to decrease gelling temperature and increase bio-compatibility and bio-elimination of MC, the molecular weight of MC was decreased using enzymatic degradation method and confirmed by gel permeation chromatography. Bio-elimination of low molecular weight (LMw) MC was confirmed with non-invasive live image and ex vivo experiment. The exenatide and FGF 21 were physically loaded 100% into LMwMC-based thermo-reversible gel and slowly released from gel with no initial bursts. Exenatide-loaded LMwMC gel showed reduction of blood glucose level for a week in type 1 diabetic animal model. FGF 21-loaded LMwMC gel reduced glucose level to normal condition and maintained over 10days in type 2 diabetic animal model. LMwMC-based thermo-reversible and injectable hydrogel provides a strong potential to be efficient protein drug delivery system for the treatment of type 1 and type 2 diabetes.

Preparation of Temperature and Water Responsive Microcapsules Containing Hydroquinone with Spray Drying Method

It was tried to prepare temperature and water responsive microcapsules containing hydroquinone as a water soluble core material with the spray drying method. Microcapsules were composed of ethyl cellulose (EC), methyl cellulose (MC) and P-N-isopropylacrylamid (PNIPAM). P-N-isopropylacrylamid and methyl cellulose were used as a temperature responsive polymer and as a water responsive polymer, respectively. Ethyl cellulose was the main shell material of microcapsule. At the microencapsulation process, the core and shell materials were dissolved in ethyl alcohol dissolving water (20 wt%) and then, spray-dried to prepare microcapsules. In the fundamental operation, the concentration and molecular weight of methyl cellulose were mainly changed. The releasing rate of hydroquinone was repressed at 40°C and increased at 20°C due to temperature responsive PNIPAM. Furthermore, responsibility to water was increased with the concentration of methyl cellulose.

Dietary Flavonoid Apigenin is not Effective in Preventing Development of a Bleomycin-Induced Murine Model of Scleroderma

Objective, Systemic sclerosis is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. The dietary flavonoid apigenin has been shown to reduce expression of the myofibroblast phenotype and to inhibit contraction of collagen gels. We investigated the effect of apigenin on the prevention and treatment of a modified bleomycin-induced animal model of scleroderma. Methods, Recently, we successfully induced scleroderma by weekly subcutaneous injections of bleomycin using a thermo- reversible combination gel composed of low molecular weight methylcellulose, A weekly subcutaneous injection of methylcellulose gel loaded with bleomycin induced focal skin fibrosis on the back skin and fibrotic phenotype of lung tissue in mice. The histologic examination of skin and lungs, collagen assay of lungs, and expression of connective tissue growth factor were investigated. Results, Daily intra-peritoneal injection of 1.0 mg/kg or 2.5mg/kg of apigenin starting a week before the bleomycin injections failed to prevent the development of skin fibrosis and reduce the fibrotic phenotypes of skin and lung tissue, Conclusion. Although some in vitro experiments have supported a potential role of apigenin in the treatment of fibrosis, dietary flavonoid apigenin is not effective in preventing development of a bleomycin-induced murine model of scleroderma.

A convenient method for producing the bleomycin-induced mouse model of scleroderma by weekly injections using a methylcellulose gel

Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. An animal model of SSc, the bleomycin-induced mouse model, has been established and used extensively to investigate the pathogenesis of SSc and to seek novel therapeutic agents. We recently developed thermo-reversible combination gels that can be injected subcutaneously and are made in aqueous solution by forming a complex coacervate with the substance of interest and cationic macromolecules, followed by co-formulation with methylcellulose (MC) as a negative thermosensitive polysaccharide. The objective of this study was to demonstrate whether weekly injections of bleomycin using combination gels loaded with bleomycin can induce the skin fibrosis model of SSc in susceptible mouse strains. A low molecular weight MC (4%) gel with 4.5% ammonium sulfate was made in aqueous solution, and mixed with bleomycin. This was injected subcutaneously into female C3H/He mice at weekly intervals. Control mice were injected with the gel made with phosphate-buffered saline. After 4 weeks, histological examination and gene expression assays of cytokines were performed. Examination in vitro showed that more than 80% of the bleomycin was released from the gel by the 4th day. Histological examination showed that dermal thickness increased in the MC-bleomycin-injected group compared with the control, and semi-quantitative analysis indicated that the extent of inflammation did not differ between the groups. In the MC-bleomycin-injected group, dermal fibrosis assessed with the Masson-Trichrome stain and numbers of alpha-smooth muscle actin-positive fibroblastic cells also increased. The procedure for inducing scleroderma in which bleomycin is injected weekly as an easily-made gel system using methylcellulose, can induce dermal fibrosis in susceptible mice without causing inflammation. We believe this system represents a time- saving and convenient procedure that should facilitate research on SSc.

Development and In-Vitro Clinical Study of Tinidazole - Chlorhexidine Gluconate ophthalmic suspension for Treatment of Keratitis

A new model aqueous micro fine suspension of tinidazole (TND) was developed on the basis of the combination with chlorhexidine gluconate to be useful in treatment of ungal corneal infection or ulcer (fungal keratitis). In vitro clinical study for TND - chlorhexidine gluconate showed a significant antifungal activity against certain species of fungi isolated from patients with corneal ulcer . Propylene glycol (PG) was chosen because it is known as a good solubilizer , it could be used as a tonicity adjustment agent in appropriate concentration & it is nontoxic . An enhancement in the solubility of TND was achieved also by interaction with a non-ionic surfactant polysorbate 80 (Tween80) and PG. .
 The models prepared by using PG were showed some practical advantages over the models containing a combination of PG and non –ionic surfactant polysorbate 80 (Tween 80) , by enhancement the in vitro dissolution & releasing of TND suspension .Previous histological studies have shown that these additives used not cause eye irritation. The prepared models showed high physiological tolerance onrabbit eye. Moreover high molecular weight methylcellulose (MC) was effective to create appropriate viscosity that was maintained unchanged after heatsterilization.

Effects of molecular weight on thermoreversible gelation and gel elasticity of methylcellulose in aqueous solution

Aqueous solutions of two methylcellulose (MC) polymers with different molecular weights ( M w=100,000 and 400,000) have been studied. The thermoreversible gelation `properties and the gel elasticity were measured as a function of polymer concentration by means of micro differential scanning calorimetry and rheology, respectively. The experimental results prove that the aqueous solutions of MC are completely thermoreversible and the thermoreversibility of MC is independent of either polymer concentration or molecular weight. The total enthalpy required for the sol–gel transition is a linear function of polymer concentration, which is again independent of molecular weight. The quasi-equilibrium modulus G e could be scaled with concentration c as G e∼ c 2.19 ( c>1.0 wt%) and G e∼ c 3.12 ( c<1.0 wt%) for the high molecular weight MC, while G e∼ c 3.12 and (c<1.0 wt%)for the low molecular weight MC. At the same concentration of MC, with increasing molecular weight, G e increases while the heat absorbed during the sol–gel transition remains constant.

Lyophilised wafers as a drug delivery system for wound healing containing methylcellulose as a viscosity modifier

Lyophilised wafers have potential as drug delivery systems for suppurating wounds. A dual series of wafers made from low molecular weight sodium alginate (SA) and xanthan gum (XG) respectively, modified with high molecular weight methylcellulose (MC) were produced. The swelling and flow properties of these wafers on model suppurating surfaces were both qualitatively and quantitatively investigated. The wafers instantaneously adhered to the surfaces, absorbing water and transforming from glassy, porous solids to highly viscous gels. The rate at which this occurred varied for the series studied with clear distinctions between the behaviour of SA and XG systems. For SA wafers there was a distinct relationship between the flow-rate and MC content. Increased amounts of MC decreased the rate at which the SA wafers flowed across a model gelatine surface. Flow rheometry was used to quantify the effect of increased MC content on both series of wafers and for the SA series, highlighted a substantial increase in apparent viscosity as a function of incremental increases in MC content. These results reflected those from the gelatine model. Observations of the reluctance of a swollen, unmodified XG wafer to flow compared with the relative ease of unmodified, low molecular weight SA was attributed to the yield stress characteristic of xanthan gels. XG is known to exhibit complex, loosely bound network structures in solution via the association of helical backbone structures. The inclusion of sodium fluorescein as a visible model for a soluble drug highlighted the potential of lyophilised wafers as useful drug delivery systems for suppurating wounds.

Formation of junction zones in thermoreversible methylcellulose gels

AbstractTo analyze the structure of junction zones formed in methylcellulose (MC) gel, the modified Eldridge–Ferry method was applied to phase diagrams for aqueous solutions of different molecular weight MCs derived from micro‐DSC, small‐angle X‐ray scattering, and visual inspection. The results suggested that junctions in MC gels took thin, rodlike fringed‐micellar crystallites. The junction multiplicity s decreased from 4.3 for low‐temperature melting gels to 2.0 for high‐temperature melting gels. With increasing molecular weight, the number ζ of statistical units in a junction along a single chain increased from 27 to 54. Because the number depends sensitively on the enthalpy of bonding per mole of the repeat units of MC, our estimate is considered to give an upper bound to the junction length. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci B: Polym Phys 39: 943–946, 2001

Thermoreversible gelation and phase separation in aqueous methyl cellulose solutions

We derived typical phase diagrams for aqueous solutions of methyl cellulose (MC) of different molecular weights via micro-differential scanning calorimetry, small-angle X-ray scattering, and visual inspection. The phase diagrams showed the cooccurrence of gelation and phase separation and qualitatively agreed with the theoretically calculated diagrams. The sol–gel transition line and phase separation line of a lower critical solution point type shifted toward lower temperatures and lower concentrations with an increase in the MC molecular weight. The sol–gel transition line intersected at a temperature higher than the critical point of the phase separation; therefore, both sol–gel phase separation and gel–gel phase separation were possible, depending on the temperature. Specifically, through visual inspection of a high molecular weight MC sample in the critical temperature region, we observed phase separation into two coexisting gels with different polymer concentrations. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 91–100, 2001

Gel‐sol transition of methylcellulose

AbstractThe gelation mechanism of aqueous solutions of methylcellulose (MC) with different molecular weights was studied by small deformation oscillation rheological measurments and differential scanning calorimetry (DSC). The gelation is promoted by the increase in molecular weight of MC: the elastic modulus becomes larger, the gelation occurs at lower temperatures and the DSC peaks accompanying the gel‐sol transition become sharper. Cooling DSC curves split into two peaks, indicating that the gel‐to‐sol transition occurred via two steps.

The molecular weight of methyl cellulose used in pharmaceutical formulation

Methyl cellulose is used extensively in pharmacy as a thickener, emulsifier and stabilizer in liquid and semi-solid formulations and as a binder and film-former in tablet and film coating formulations. It is prepared by the alkaline degradation of cellulose fibres which are subsequently treated with methyl chloride. The basic repeating structure is one of the anydroglucose units with some of the hydroxyl groups substituted by methoxyl groups. The methyl cellulose used in pharmaceutical formulation has a degree of substitution (i.e. the average number of hydroxyl groups substituted per anhyd..,oglucose unit) of between 1.64 and 1.92 corresponding to a methoxyl content of between 27.5 and 31.5~ w/w. An advantage of this polymer is its availability in a wide range of grades with varying viscosity designations representing the viscosity of a 2% w/w aqueous solution of the polymer at 20°C. Since a knowledge of the molecular weight of these various viscosity grades is of importance io the pharmaceutical formulator, especially the one involved in film coating formulation where the molecular weight of the polymer used has an important effect on the mechanical properties of the resultant films (Rowe, 1976, 1980, 1982) and on the incidence of film cracking (Rowe and Forse, 1980), it is pertinent to review and compare the literature data on this polymer. Data relating the molecular weight of a polymer to its viscosity in a solvent system are usually expressed in the form of the Mark-Houwink equation: