Molecular Weight Hydroxypropyl Methylcellulose Research Articles

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Hydroxypropyl methylcellulose-based micro- and nanostructures for encapsulation of melanoidins: Effect of electrohydrodynamic processing variables on morphological and physicochemical properties

Electrohydrodynamic processing (EHDP) allows the use of a wide range of biopolymers and solvents, including food-grade biopolymers and green solvents, for the development of micro- and nanostructures. These structures present a high surface-area-to-volume ratio and different shapes and morphologies. The aim of this work was to design and produce hydroxypropyl methylcellulose (HPMC)-based micro- and nanostructures through EHD processing using green solvents, while exploring the influence of process and solution parameters, and incorporating a bioactive extracted from a food by-product. Low (LMW) and high (HMW) molecular weight HPMC have been used as polymers. The design-of-experiments methodology was used to determine the effects of process parameters (polymer concentration, flow rate, tip-to-collector distance, and voltage) of EHDP on the particle and fibre diameter, aspect ratio, diameter distribution, aspect ratio distribution, and percentage of fibre breakage. Additionally, melanoidins extracted from spent coffee grounds were encapsulated into the HPCM-based structures at a concentration of 2.5 mg melanoidins/mL of the polymer solution. Polymer solutions were characterised regarding their viscosity, surface tension and conductivity, and showed that the incorporation of melanoidins increased the viscosity and conductivity values of the polymer solutions. The developed structures were characterised regarding their thermal properties, crystallinity and morphology before and after melanoidin incorporation and it was observed that melanoidin incorporation did not significantly influence the characteristics of the produced micro- and nanostructures. Based on the results, it is possible to envision the use of the produced micro- and nanostructures in a wide range of applications, both in food and biomedical fields.

Optical, mechanical and electrical properties of HPMC-AuNPs nanocomposite films

The current study reports the production of gold nanoparticles (AuNPs) employing low molecular weight hydroxypropyl methyl cellulose (HPMC) as a reducing and stabilizing agent of chloroauric acid (HAuCl4). The existence of gold nanoparticles (AuNPs) was established by a color conversion from light yellow to light purple, as well as UV–Visible absorption spectroscopy (UV–Vis) with the surface Plasmon resonance (SPR) in the 545–550 nm range. Scanning electron microscopy (SEM) was used to examine the surface morphology of the fabricated nanocomposites. Mechanical properties of the samples were changed as the concentrations of the synthesized nanoparticles increased. While, electrical properties were determined using an impedance analyzer, which revealed a decrease in dielectric loss and dielectric constant as frequency increased.

Fabrication and characterization of HPMC-AuNPs nanocomposite films

This paper presents the in-situ generation of gold nanoparticles (AuNPs) by reducing chloroauric acid (HAuCl4·H2O) with low molecular weight hydroxypropyl methylcellulose (HPMC), and HPMC-AuNPs nanocomposites are developed via solution casting method. The generation of AuNPs was initially established by a swap in color from pale yellow to purple, and then by UV–Visible (UV–Vis) spectrophotometry with the surface plasmon resonance (SPR) band observed at λ = 550 nm. The functional groups accountable for the reduction of gold ions to neutral gold atoms were identified using Fourier transform infrared spectroscopy (FT-IR). The crystalline form of the AuNPs with FCC structure was shown by X-ray diffraction (XRD) studies. The size and shape evolution of the different shaped AuNPs are confirmed by the transmission electron microscopy (TEM) study which divulged the presence of triangular plate, hexagonal, quasi spherical, isosceles trapezoid and truncated triangular morphologies of the AuNPs with an average size of 12.5 nm.

Evaluating the efficacy of different curcumin polymorphs in transdermal drug delivery

Curcumin exists in three polymorphic forms: one monoclinic form and two orthorhombic forms. This work aims to investigate the efficacy of curcumin polymorphs in transdermal drug delivery by formulating curcumin polymorphs and their incorporation in polymeric films. Monoclinic form, Form 1, was precipitated by liquid antisolvent technique from acetone solutions, whereas orthorhombic form, Form 2, was obtained by vacuum evaporation of solutions of curcumin in a mixed solvent of chloroform and hexane (60:40%v/v). The other orthorhombic form, Form 3, was precipitated from dimethylsulfoxide solutions. All three curcumin polymorphs were incorporated into polymeric films made of low molecular weight hydroxypropyl methyl cellulose (HPMC E5LV) along with different plasticizers, and permeation enhancers. Radical scavenging activity and cytotoxicity of curcumin polymorphs on human melanoma cell lines were evaluated. Water uptake, in-vitro release, and in-vitro permeation studies on HPMC films loaded with curcumin polymorph were carried out. Cytotoxicity studies on human melanoma cells (SK-MEL-28) showed that Form 2 results in the highest cell inhibition. Among all three curcumin polymorphs, the free radical scavenging activity of Form 3 was found to be the highest. HPMC films loaded with Form 3 exhibited higher water uptake and higher curcumin release profiles at pH of 5.5 (95.3% in 20 h) and pH 7.4 (79.8% in 20 h) as well as the highest in-vitro permeation compared to the other two curcumin forms. Overall, orthorhombic curcumin polymorphs (i.e., Form 2 and Form 3) showed a higher propensity for transdermal drug delivery as compared to the monoclinic curcumin (Form 1).

Effect of hydroxypropyl methylcellulose molecular weight on supramolecular structures and properties of HPMC/sodium citrate photophobic films

Photophobic (white) films were prepared by mixing hydroxypropyl methylcellulose (HPMC) of different molecular weights with sodium citrate (SC). Wide angle X-ray diffractometry, small angle X-ray scattering, scanning electron microscopy, dynamic mechanical analysis, whiteness determination and texture analysis were used to investigate the effect of HPMC molecular weight on the aggregation structures and properties of HPMC film. The crystalline integrity decreased with the increased molecular weight of HPMC for these HPMC/SC films. Similar crystallinity was observed for 6HPMC/SC and 15HPMC/SC, which was larger than that of 50HPMC/SC. All the three HPMC/SC film showed surface fractal structure with similar Ds. With the increasing molecular weight of HPMC, the HPMC/SC film showed honeycomb structures with smaller holes and more compact porous structure, Tg first increased and then decreased a little, the tensile strength and elongation increased with the increasing HPMC molecular weight. 50HPMC/SC films with the smallest pores showed the largest whiteness. A new Tg' peak was observed for HPMC/SC film.

Development of Itraconazole Tablets Containing Viscous KinetiSol Solid Dispersions: In Vitro and In Vivo Analysis in Dogs.

The formulation factors relevant to developing immediate and controlled release dosage forms containing poorly soluble drugs dispersed in amorphous systems are poorly understood. While the utility of amorphous solid dispersions is becoming apparent in the pharmaceutical marketplace, literature reports tend to concentrate on the development of solid dispersion particulates, which then must be formulated into a tablet. Amorphous solid dispersions of itraconazole in high molecular weight hydroxypropyl methylcellulose were prepared by KinetiSol® Dispersing and tablets were formulated to immediately disintegrate or control the release of itraconazole. Formulated tablets were evaluated by two non-sink dissolution methodologies and the dosage form properties that controlled the gelling tendency of the dispersion carrier, hydroxypropyl methylcellulose, were investigated. Selected formulations were evaluated in an exploratory beagle dog pharmacokinetic study; the results of which indicate potential for a prolonged absorption phase relative to the commercially extruded control.

Multiple Thermal Gelation of Hydroxypropyl Methylcellulose and Kappa-Carrageenan Solutions and their Interaction with Salts

The multiple gelation behavior of aqueous solutions of kappa-carrageenan (KCG) and low molecular weight hydroxypropyl methylcellulose (HPMC) was studied with the presence of various salts. Multiple gelation behavior of aqueous solutions of HPMC/KCG/salt mixture were found. The shear viscosity of HPMC/KCG blend increased by one orders of magnitude, while the viscosity of HPMC/KCG/potassium chloride (KCl) mixture increased by three orders of magnitude as compared to HPMC solution at temperatures below apparent gelation. The dynamic elastic modulus of HPMC/KCG blend increased by two orders of magnitude, while the elastic modulus of HPMC/KCG/potassium chloride (KCl) mixture increased by three orders of magnitude as compared to HPMC solution at temperatures below apparent gelation temperature. The gel elastic modulus of the solution blend of HPMC/KCG/salt mixture decreased in the order of KCl > NaCl > CaCl2. Thermal analysis revealed a linear relationship between the depression of melting temperature and the salt concentrations, which is independent of KCG. The free water content computed by enthalpy data showed that free water content decreased with increasing salt concentrations. The secondary peak which typically associated with bound water appeared in the mixture of HPMC and KCG in the presence of KCl. As the concentrations of KCl salt increased, the bound water peak also amplified and lifted to a higher temperature.

Effect of temperature on the wetting behavior of hydroxypropyl methylcellulose in a twin-screw granulator

Temperature has rarely been examined in twin-screw wet granulation despite the obvious capabilities of the extruder for operating at elevated temperatures. The present work investigates the wetting behavior of a mixture of powders with different sorption characteristics at various temperatures to explain the unique granulation behavior witnessed with high molecular weight hydroxypropyl methylcellulose in a twin-screw extruder. The work studies the twin-screw granulation of a controlled release formulation at three different temperatures, namely 30°C, 55°C and 80°C and attempts to interpret the granular properties of collected samples relative to characterized moisture sorption isotherms measured for the individual ingredients as well as the mixtures. A result of higher temperature processing was reduced coarse particles and a final product with more spherical granules. Increasing temperature was found to reduce water absorption capacity among the ingredients, especially hydroxypropyl methyl cellulose and microcrystalline cellulose, leaving more of the added water for particle bridging. The gel layer of hydroxypropyl methyl cellulose particles was diminished by the higher temperatures which did not appear to impact the strength of the particle bridges formed. Inclusion of a more hydrophobic ingredient like acetaminophen complicates the distribution of water in a granule.

Tailoring the mucoadhesive and sustained release characteristics of mesalamine loaded formulations for local treatment of distal forms of ulcerative colitis

Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal systems to manage distal forms of ulcerative colitis was studied. The High molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined with hydrophilic surfactants to control polymer hydration process allowing optimization of the mucoadhesive and controlled drug release properties for the rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared and in vitro characterized using scanning electron microscope, differential scanning calorimetry and X-ray diffraction techniques. Rectal formulations were prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG) combination bases. The developed rectal formulations were investigated for physical, mucoadhesion, in-vitro drug release and swelling characteristics. Results revealed acceptable physical characteristics of the prepared formulations with good content uniformity and minimum weight variation. Sustained release patterns of MS form HPMC K4M based formulations were observed. Formulations prepared using high proportions of the polymer or PEG 400 showed higher extent of mucoadhesion, swelling and greatly extended drug release time. Efficacy of an optimized formulation was assessed using the acetic acid induced colitis model in rats and compared to a reference polymer-free formulation of the drug. Clinical evaluation included bleeding from rectum, consistency of animal stool and colon/body weight ratio. Furthermore, histopathological analysis was carried out to evaluate the degree of inflammation and mucosal damage. Overall results showed a significant enhancement in the clinical pictures and colon histopathology of animals treated by the sustained release mucoadhesive formulation compared to the reference polymer free formulation and the non-treated colitis group.

Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets

The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n = 6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.

Prevention of peritoneal adhesions using polymeric rheological blends

The effectiveness of rheological blends of high molecular weight hyaluronic acid (HA) and low molecular weight hydroxypropyl methylcellulose (HPMC) in the prevention of peritoneal adhesions post-surgery is demonstrated. The physical mixture of the two carbohydrates increased the dwell time in the peritoneum while significantly improving the injectability of the polymer compared with HA alone. HA–HPMC treatment decreased the total adhesion area by ∼70% relative to a saline control or no treatment in a repeated cecal injury model in the rabbit. No significant cytotoxicity and minimal inflammation were associated with the blend. Furthermore, no chemical or physical processing was required prior to their use beyond simple mixing.

Monovalent and divalent salt effects on thermogelation of aqueous hypromellose solutions

The effect of salt on gelation behavior of concentrated low molecular weight Hydroxypropyl methylcellulose (HPMC, Hypromellose) solutions were investigated by using rheology measurements. Various gelation matrices were used to characterize gelation point as a function of salt concentrations. It was found that gelation temperature identified by frequency-independent loss tangents is similar to the gelation temperature at which minimum elastic modulus, G′, occurred during heating process. Thermal analysis showed that the melting temperature decreased linearly with increasing ion concentration of salts. The bound water analysis showed that the bound water increased as the salt concentration increased. Secondary peaks that represent the freezable bound water were also observed for solutions with NaCl and KCl.

<i>In Vitro</i> and <i>In Vivo</i> Evaluation of Diclofenac Sodium Gel Prepared with Cellulose Ether and Carbopol 934P

Purpose: To develop diclofenac sodium gel using high molecular weight hydroxypropyl methylcellulose (HPMC) and Carbopol 934P for topical and systemic delivery.Methods: Diclofenac sodium gel was prepared with HPMC K100M and Carbopol 934P as gelling agents. The formulations were examined for pH, spreadability, consistency, viscosity, homogeneity, drug content and stability. In vitro drug release was evaluated using Franz diffusion cell. Carrageenaninduced rat paw oedema model was used for the evaluation of the anti-inflammatory activity of the gels. A commercial diclofenac sodium gel product was used as the reference drug.Results: Formulations containing glycerin as permeation enhancer gave drug release patterns comparable to that of the reference product. The drug content of F2, F5 and F9 was 99.81, 99.75 and 99.96 %, respectively. Accelerated stability results showed no significant variation in the appearance and drug release after storage for 3 months.Conclusion: Diclofenac sodium gel containing HPMC K100M and Carbopol 934P exhibited pronounced anti-inflammatory activity and could be further developed for topical and systemic delivery..Keywords: Diclofenac sodium, Anti-inflammatory, Hydroxypropyl methylcellulose, Carbopol, Drug release, Glycerin

Competition of Thermodynamic and Dynamic Factors During Formation of Multicomponent Particles via Spray Drying

As psicose cannot be spray dried because of its low glass transition temperature (T(g)), additives have been used to manufacture spray-dried particles. Its thermodynamic miscibility with each additive was evaluated by thermal analysis and C solid-state nuclear magnetic resonance. Aspartame was miscible with psicose at all ratios, and spray-dried particles were obtained when T(g) of the mixture was higher than the outlet temperature of the spray dryer, where 30 wt % of psicose was loaded. poly(vinylpyrrolidone) and cluster dextrin were partially miscible with psicose, with a maximum loading of 40 wt %. When polymeric excipients were used, their mixing behavior with psicose was affected by the dynamic factor during the spray drying, that is, enhanced phase separation due to the molecular-weight difference. The T(g) value of the polymer-rich phases, which were likely to form shell layers on the surfaces, played an important role in determining availability of the spray-dried particles. Hydroxypropyl methylcellulose (HPMC) offered a very effective loading capacity of 80 wt %, due to distinct phase separation to form shell phase with a very high T(g). Because molecular weight of HPMC was the smallest among the polymeric excipients, the thermodynamic miscibility seemed to affect the dynamic phase separation. These results provide useful information for preparing multicomponent spray-dried particles.

Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses

Symptoms of contact lenses induced dry eye (CLIDE) are typically treated through application of macromolecular re-wetting agents via eye drops. Therapeutic soft contact lenses can be formulated to alleviate CLIDE symptoms by slowly releasing comfort agent from the lens. In this paper, we present an extended wear silicone hydrogel contact lens with extended, controllable release of 120 kDa hydroxypropyl methylcellulose (HPMC) using a molecular imprinting strategy. A commercial silicone hydrogel lens was tailored to release approximately 1000 μg of HPMC over a period of up to 60 days in a constant manner at a rate of 16 μg/day under physiological flowrates, releasing over the entire range of continuous wear. Release rates could be significantly varied by the imprinting effect and functional monomer to template ratio (M/T) with M/T values 0, 0.2, 2.8, 3.4 corresponding to HPMC release durations of 10, 13, 23, and 53 days, respectively. Lenses had high optical quality and adequate mechanical properties for contact lens use. This work highlights the potential of imprinting in the design and engineering of silicone hydrogel lenses to release macromolecules for the duration of wear, which may lead to decreased CLIDE symptoms and more comfortable contact lenses.

P11-12. A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140

BackgroundCervicovaginal (CV) tissue is the primary site for HIV transmission and a major reservoir for viral replication. Therefore, a successful vaccine strategy should induce potent immune responses at this mucosal surface. One potential method for achieving a localised immuneresponse is to administer the antigen directly to the CV tissue (Marx et al., 1993, Wassen et al., 1996). The aim of the study was to evaluate the in vitro release characteristics oflyophilised hydroxypropylmethylcellulose (HPMC) gel inserts containing HIV envelope protein CN54gp140 either as stand-alone formulations or located within a novel rod-insert vaginal ring device (RIVR).MethodsVaginal gel formulations comprising either low or high molecular weight (MW) HPMC and CN54gp140 (0.25% w/w) were prepared. The gels were injected into silicone elastomer tubing, cut to 40 mm lengths, and then lyophilised to produce solid rod inserts. In vitro release testing was performed on rod inserts alone and rod insert vaginal rings (RIVRs) containing two CN54gp140-loaded rod inserts. Release of gp140 was quantified by ELISA.ResultsRelease of CN54gp140 from rods prepared from low MW HPMC was similar for both inserts alone and rings containing inserts (99% cf. 90% over two hr). Release from the high MW inserts was significantly slower and more sustained than the low MW formulations. Also, CN54gp140 release from high MW rod inserts rings (68% of theoretical over 48 hr) was significantly more sustained than high MW inserts alone (86% over 24 hr).ConclusionThe study demonstrates that CN54gp140 (i) maintains its antigenicity during the preparation of HPMC lyophilised rod inserts, and (ii) may be administered in a sustainedmanner when the inserts are placed into an RIVR device. This stable, sustained-release formulation strategy has the potential to induce stronger immune responses andimmune memory upon vaginal administration (Zhao and Leong, 1996; Lofthouse, 2002).

Formulation and evaluation of pectin-hydroxypropyl methylcellulose coated curcumin pellets for colon delivery

High molecular weight hydroxypropyl methylcellulose (HPMC) and biodegradable pectin were used for coating the pellets containing curcumin, to be released in the colon. The prepared pellets were freeflowing. in vitro release of curcumin remained intact up to pH 3.0, disintegrated at pH 7.2, and released up to 12 hours. The ideal batch (1:3) showed minimum release at pH 1.2 and maximum release at pH 6.8, and an increased amount of curcumin in the blood stream(1.287 μg/ml) was achieved when compared with pure curcumin (0.5 μg/ml). The drug release was retarded by the high concentrationand greater thickness of the coating of HPMC on the pellets. Release kinetics of the preparation shows a non-Fickian or anamolous diffusion or matrix erosion.

Bio-fluid uptake and release of Indomethacin of direct-compressed HPMC tablets

Tablets of three different grades of hydroxypropyl methyl cellulose (HPMC), having different viscosity, were prepared using the direct-compression technique with no additive or binder. The fluid uptake behavior of these HPMC tablets was studied in three types of bio-media – water, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). The amount of fluid uptake by the tablets followed a power law relationship with time for all three media. Variants such as pH value, type of salts and salt concentration in the media were found to have little influence on the swelling process for the tablet. On the contrary, viscosity and molecular weight of HPMC were the controlling parameters for the swelling process. Subsequently, Indomethacin was added in certain percentage to the tablets as a model drug. It was to examine and elucidate drug releasing properties of the HPMC tablets. The possible mechanisms involved in the process of drug dispersion are proposed and discussed.

Compression and compaction properties of plasticised high molecular weight hydroxypropylmethylcellulose (HPMC) as a hydrophilic matrix carrier

The compression and compaction properties of plasticised high molecular weight USP2208 HPMC were investigated with the aim of improving tablet formation in HPMC matrices. Experiments were conducted on binary polymer–plasticiser mixtures containing 17 wt.% plasticiser, and on a model hydrophilic matrix formulation. A selection of common plasticisers, propylene glycol (PG) glycerol (GLY), dibutyl sebacate (DBS) and triacetin (TRI), were chosen to provide a range of plasticisation efficiencies. T g values of binary mixtures determined by Dynamic Mechanical Thermal Analysis (DMTA) were in rank order PG > GLY > DBS > TRI > unplasticised HPMC. Mean yield pressure, strain rate sensitivity (SRS) and plastic compaction energy were measured during the compression process, and matrix properties were monitored by tensile strength and axial expansion post-compression. Compression of HPMC:PG binary mixtures resulted in a marked reduction in mean yield pressure and a significant increase in SRS, suggesting a classical plasticisation of HPMC analogous to that produced by water. The effect of PG was also reflected in matrix properties. At compression pressures below 70 MPa, compacts had greater tensile strength than those from native polymer, and over the range 35 and 70 MPa, lower plastic compaction values showed that less energy was required to produce the compacts. Axial expansion was also reduced. Above 70 MPa tensile strength was limited to 3 MPa. These results suggest a useful improvement of HPMC compaction and matrix properties by PG plasticisation, with lowering of T g resulting in improved deformation and internal bonding. These effects were also detectable in the model formulation containing a minimal polymer content for an HPMC matrix. Other plasticisers were largely ineffective, matrix strength was poor and axial expansion high. The hydrophobic plasticisers (DBS, TRI) reduced yield pressure substantially, but were poor plasticisers and showed compaction mechanisms that could be attributed to phase separation. The effect of different plasticisers suggests that the deformation characteristics of this HPMC in the solid state is dominated by hydroxyl mediated bonding, rather than by hydrophobic interactions between methoxyl-rich regions.