Hydroxypropyl Methylcellulose Blends Research Articles

Effect of annealing on morphologies and performances of hydroxypropyl methylcellulose/hydroxypropyl starch blends

AbstractThe morphologies and performances of the blends of hydroxypropyl methylcellulose (HPMC), which is a thermal gel, and hydroxypropyl starch (HPS), which is a cooling gel, provides a scientific model to understand the relationship between the microstructure and performance of the unique thermal/cooling gel system. The films based on these blends have been developed for various applications, such as food packaging and medicine capsules, mainly for improving processibility. The morphologies and performance of the blends strongly depend on annealing or storage conditions and time since they are neither miscible nor compatible. This work focuses on the effects of storage conditions and time on the morphologies and performance of the blend films. It was found that the morphologies of the blend system depend on temperature, moisture, and annealing time. Correspondently, the gas permeability and mechanical properties of the film were also environmentally and time dependent. When HPS is continuous phase, the annealing results in starch recrystallization, which increases rigidity. When HPMC is the continuous phase, the materials showed less moisture sensitivity. Starch recrystallization and phase separation, which resulted in microcracks on the surface of the films, are the main reasons for the reduction in gas barrier and elongation. This work will study these issues using scanning electron microscope, X‐ray diffraction, mechanical testing and establish their relationship.

Chemical mapping analysis of compatibility in gelatin and hydroxypropyl methylcellulose blend films

Blending different polymers for composite formulations can improve the functionalities of the products. The compatibility between hydroxypropyl methylcellulose (HPMC) and gelatin was studied using Chemical mapping analysis such as synchrotron micro-infrared spectroscopy (μSR-FTIR) and confocal Raman microscopy. The interface and phase composition of the blend films with varying ratios of gelatin and HPMC were analyzed in detail. It was found that the distribution patterns of continuous matrices and dispersed phases changed with varying concentrations of the components. Raman spectroscopy based imaging analysis showed that HPMC easily aggregated to form continuous phases. Both μSR-FTIR and Raman microscopic analysis confirmed the existence of intermediate phases in the composites from the molecular interactions between the two components. Overall, the Chemical mapping techniques were useful to study the phase composition of composites of polysaccharides and proteins.

Miscibility studies of plastic-mimetic polypeptide with hydroxypropylmethylcellulose blends and generation of non-woven fabrics

In the current investigation, the results of viscometric measurements, thermal property, SEM, XRD and FTIR of the polymer blends containing synthetic plastic-based polypeptide (PLP) with hydroxypropylmethylcellulose (HPMC) on miscibility is discussed. Various interaction parameters; KH, Δ[η]m, ΔB, μ, α, β and ΔK indicated the miscibility of polypeptide/HPMC up to 40% of the PLP in the blend at room temperature. The calorimetric results a single glass transition event for miscible systems. Further, the results were aligned with the scanning electron microscope and XRD analysis. Details concerning the nature of interactions in these systems and how they are influenced by the peptide proportion in the blends are discussed. The thermo gravimetric analysis manifested the improved thermal stability of the blends than their individual polymers. Additionally, the blend solutions were fabricated into non-woven fabrics with electrospinning technique, which may be a good candidate for pharmaceutical and biomedical applications.

Design, in vitro/in vivo evaluation of meclizine HCl-loaded floating microspheres targeting pregnancy-related nausea and vomiting

The aim of this study was to investigate whether floating microspheres prepared from polymer blends of hydroxypropyl methylcellulose in combination with either Eudragit S100 or Eudragit RS100 could improve the systemic bioavailability of the antiemetic drug; meclizine HCl (MCZ). Floating microspheres containing MCZ were prepared by emulsion solvent evaporation method. The influence of different polymer blend compositions on various formulation parameters and in vitro release characteristics of the prepared microspheres was investigated. In addition, the in vivo pharmacokinetic profile of an optimized formula was evaluated. The mean particle size of prepared microspheres ranged from 290 to 383 μm. The percent drug entrapment efficiency varied between 51.9 ± 0.3% to 91.6 ± 0.7%. The formulated microspheres exhibited excellent floating ability. In vitro release profiles of floating microspheres indicated a rapid initial release followed by a sustained drug release for up to 24 h. The pharmacokinetic data affirmed the sustained effect of the optimized formula as indicated by the prolonged tmax, compared to the plain drug. Furthermore, the optimized formula showed higher relative bioavailability (154.25%), compared to the plain drug. These results suggest that MCZ floating microspheres might represent potential alternative to conventional MCZ oral formulations, with a higher and sustained therapeutic efficacy.

Effect of plasticizers on microstructure, compatibility and mechanical property of hydroxypropyl methylcellulose/hydroxypropyl starch blends

Polymer film blends of hydroxypropyl methylcellulose (HPMC) and hydroxypropyl starch (HPS) were produced with an incorporation of three different plasticizers, including polyethylene glycol (PEG), glycerol and 1, 2-propylene glycol (PG) respectively, and the influence of these plasticizers were compared and studied by X-ray Diffraction (XRD), small angel X-ray Scattering (SAXS), optical microscope and dynamic mechanical analysis (DMA). Results showed that multi-scale structure of the blends were greatly affected by the plasticizers and therefore caused significant changes in mechanical properties. In the course, blends with glycerol presented lamellar structure rather than self-similar structure. Moreover, crystalline degree was increased with an order of glycerol > PEG > PG, whereas the compactness of amorphous region of all samples was decreased by PEG and PG.

Formulation, Characterization, and Optimization of Captopril Fast-Dissolving Oral Films.

This work aimed to using optimization study to formulate a patient-friendly captopril fast-dissolving oral film with satisfactory disintegration time. Films were made with pullulan and hydroxypropyl methyl cellulose (HPMC) by using the solvent-casting method. Cellulose nanofiber (CNF) was used as a compatibilizer and glycerine was used as a plasticizer. In order to find an optimum formulation, a response surface methodology and a central composite design were employed. The concentration percentages of pullulan and glycerine were considered to be the design factors. Disintegration time, tensile strength, percent elongation at break, and folding endurance were considered to be the responses. The results showed that CNF improved the compatibility and tensile strength of the pullulan and HPMC blend. Also, the rigid nature of CNF reduced the film elongation but the addition of glycerine improved its flexibility. All formulations showed an acceptable uniformity content and dissolution rate. Complete dissolution for all formulations occurred within 2min. Films with 26% pullulan, 74% HPMC, 1% CNF, and 5% glycerine were reported to be optimum formulations for captopril fast-dissolving oral films, with 95% confidence levels. The in vivo comparison of optimized formulation with a conventional captopril sublingual tablet exhibited significant increase in AUC (~62%) and Cmax (~52%) and a major decrease in Tmax (~33%). The overall results showed that the captopril FDF is a promising candidate for enhanced in vivo orotransmucosal absorption.

Improved hydroxypropyl methylcellulose (HPMC) films through incorporation of amylose-sodium palmitate inclusion complexes

Polymer film blends of hydroxypropyl methylcellulose (HPMC) and amylose-sodium palmitate inclusion complexes (Na-Palm) were produced with no plasticizer, and were observed to have improved physical and gas barrier properties as compared with pure HPMC. The crystalline amylose helices incorporating the hydrophobic sodium palmitate ligand decreased the water vapor permeability of a 50/50% blended film of HPMC/Na-Palm by 40% and decreased oxygen permeability by 96%. The incorporation of 25% Na-Palm into HPMC films resulted in improved elongation, Young’s modulus and toughness. Addition of the amylose-complexes produced relatively smooth, high clarity films which had reduced solubility in neutral and acidic solutions. Increasing concentrations of Na-Palm increased film thermal resilience and increased storage modulus at high temperatures. The heat deflection temperature of the films also increased with increasing concentrations of amylose-complex; HPMC/Na-Palm film blends with >50% Na-Palm displayed almost no material deformation up to 250 °C.

New blends of hydroxypropylmethylcellulose and Gelucire 44/14: physical property and controlled release of drugs with different solubility

New blends of hydroxypropylmethylcellulose (HPMC, 4000 cps) and Gelucire®44/14 (GE) were utilized to modulate the solubility and release rate of poorly water-soluble drug in a controlled manner. HPMC was used as sustained release polymer while GE was blended as a solubilizing carrier. The binary blends of HPMC and GE with proportional ratios (0, 25, 50, 70, 100%) were prepared by three different preparation methods: simple physical mixing, solvent evaporation and hot-melting. The physical properties such as surface morphology, thermal behavior and crystallinity pattern of the binary blends without loading drugs were then characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), respectively. Finally, the ternary solid dispersions (SD) were prepared by dispersing model drugs in a binary blend. Two model drugs, water-soluble acetaminophen (AAP) and poorly water-soluble pranlukast (PLK) were applied to the binary blends. In case of AAP, HPMC retarded release rate but GE had no significant solubilizing effect due to the high AAP solubility, In contrast, the release rate of PLK was efficiently modulated release rate in a controlled manner with an aid of HPMC and GE. Surely, GE could play a key role in enhancing the dissolution rate while HPMC efficiently controlled release rate of drugs without losing drug crystallinity.

Miscibility of Itraconazole-Hydroxypropyl Methylcellulose Blends: Insights with High Resolution Analytical Methodologies.

Drug-polymer miscibility is considered to be a prerequisite to achieve an optimally performing amorphous solid dispersion (ASD). Unfortunately, it can be challenging to evaluate drug-polymer miscibility experimentally. The aim of this study was to investigate the miscibility of ASDs of itraconazole (ITZ) and hydroxypropyl methylcellulose (HPMC) using a variety of analytical approaches. The phase behavior of ITZ-HPMC films prepared by solvent evaporation was studied before and after heating. Conventional methodology for miscibility determination, that is, differential scanning calorimetry (DSC), was used in conjunction with emerging analytical techniques, such as fluorescence spectroscopy, fluorescence imaging, and atomic force microscopy coupled with nanoscale infrared spectroscopy and nanothermal analysis (AFM-nanoIR-nanoTA). DSC results showed a single glass transition event for systems with 10% to 50% drug loading, suggesting that the ASDs were miscible, whereas phase separation was observed for all of the films based on the other techniques. The AFM-coupled techniques indicated that the phase separation occurred at the submicron scale. When the films were heated, it was observed that the ASD components underwent mixing. The results provide new insights into the phase behavior of itraconazole-HPMC dispersions and suggest that the emerging analytical techniques discussed herein are promising for the characterization of miscibility and microstructure in drug-polymer systems. The observed differences in the phase behavior in films prepared by solvent evaporation before and after heating also have implications for processing routes and suggest that spray drying/solvent evaporation and hot melt extrusion/melt mixing can result in ASDs with varying extent of miscibility between the drug and the polymer.

Developing hydroxypropyl methylcellulose/hydroxypropyl starch blends for use as capsule materials

Blends of hydroxypropyl methylcellulose (HPMC) with up to 70% hydroxypropyl starch (HPS) were developed for use as hard capsule materials. Polyethylene glycol (PEG) was used as both a plasticizer and a compatibilizer in the blends. In order to prepare hard capsules for pharmaceutical application using the well-established method of dipping stainless steel mold pins into solution then drying at certain temperature, equilibrated solutions with higher solids concentration (20%) were investigated and developed. The solutions, films and capsules of the different HPMC/HPS blends were characterized by viscosity, transparency, tensile testing, water contact angle, SEM, as well as FTIR. The results showed that the blend system is immiscible but compatible in certain degree, especially after adding PEG. The hydroxypropylene groups grafted onto both cellulose and starch improved the compatibility between the HPMC and the modified starch. The higher viscosity of starch at lower temperature improved the viscosity balance of the system, which enlarged the operation window for the dipping–drying technique. The PEG increased the transparency and toughness of the various blends. By optimizing temperature and incubation time to control viscosity, capsules of various blends were successfully developed.

Characterization and Evaluation of the Release Kinetics of a Model Poorly Water-Soluble and Low Dose Drug from Matrix Tablets Composed of Blends of Swellable and Erodible Polymers: Implications for Controlled and Complete Release

The specific aim of this study was to prepare sustained release matrix tablets containing indapamide as a low dose and low water solubility model drug. The matrix formers were composed of blends of hydroxypropyl methylcellulose as a swellable polymer and methyl cellulose as an erodible polymer. The matrix tablets were prepared by the direct compression technique and they have shown robust and acceptable physical properties with a content uniformity within the acceptable limits. Lactose and microcrystalline cellulose were investigated as additives to these matrices in order to adjust and modulate the release of the drug from the matrices to achieve a release profile similar to that obtained from the reference commercial product, Natrilix ® . All matrix tablets prepared with these two additives have gave a release profile that is close to zero order kinetics, however, the matrix tablets prepared with lactose gave a release profile with closer resemblance to that of the reference product with a similarity factor (F2) of 86. This is attributed to the rapid water solubility of lactose which enhanced higher erosion of the tablets, and thus, higher dissolution and diffusion of the drug. Microcrystalline cellulose is a swellable polymer where it has resulted in delayed release of the drug with time as compared to the reference product. Investigation of the mechanism of release of the drug from the matrices indicated that erosion is the dominant mechanism of drug release from these matrices.

Optical study of poly(vinyl alcohol)/hydroxypropyl methylcellulose blends

The proposal in this study was to evaluate the optical properties of different biopolymers films. The materials used were poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC). PVA/HPMC blends were prepared by casting technique. Variations in the group coordination in the infrared region were followed. The effects of HPMC concentrations on the optical properties of the PVA films were studied by near infrared, ultraviolet/visible, transmittance, and reflectance in the spectral region 200–2500 nm. Absorption, transmittance, and reflectance spectra were used for the determination of the optical constants. The study has been also extended to include the changes in the optical parameters including the band tail width and band gap energies and extinction coefficient for the investigated films. The results indicate that the optical band gap was derived from Tauc’s extrapolation and decreases with the HPMC contents. The obtained optical parameters were found to be strongly affected by HPMC contents.

Physical Properties of Whey Protein–Hydroxypropylmethylcellulose Blend Edible Films

The formations of glycerol (Gly)-plasticized whey protein isolate (WPI)-hydroxypropylmethylcellulose (HPMC) films, blended using different combinations and at different conditions, were investigated. The resulting WPI: Gly-HPMC films were analyzed for mechanical properties, oxygen permeability (OP), and water solubility. Differences due to HPMC quantity and blend method were determined via SAS software. While WPI: Gly and HPMC films were transparent, blend films were translucent, indicating some degree of immiscibility and/or WPI-HPMC aggregated domains in the blend films. WPI: Gly-HPMC films were stronger than WPI: Gly films and more flexible and stretchable than HPMC films, with films becoming stiffer, stronger, and less stretchable as the concentration of HPMC increased. However, WPI: Gly-HPMC blended films maintained the same low OP of WPI: Gly films, significantly lower than the OP of HPMC films. Comparison of mechanical properties and OP of films made by heat-denaturing WPI before and after blending with HPMC did not indicate any difference in degree of cross-linking between the methods, while solubility data indicated otherwise. Overall, while adding HPMC to WPI: Gly films had a large effect on the flexibility, strength, stretchability, and water solubility of the film polymeric network, results indicated that HPMC had no effect on OP through the polymer network. WPI-HPMC blend films had a desirable combination of mechanical and oxygen barrier properties, reflecting the combination of hydrogen-bonding, hydrophobic interactions, and disulfide bond cross-linking in the blended polymer network.

Miscibility, thermal, and mechanical studies of hydroxypropyl methylcellulose/pullulan blends

AbstractMiscibility of blends of hydroxypropyl methylcellulose (HPMC) and Pullulan in common solvent water were studied by viscometry, ultrasonic, density, and refractometric methods at 30 and 40°C. Further the blend films of HPMC and Pullulan were prepared by solution casting method and characterized by Fourier transform IR spectroscopy (FTIR), scanning electron microscopy, tensile measurements, thermogravimetric, and differential scanning calorimetric (DSC) methods. Using the viscosity data, interaction parameters were computed and it suggests that the blend is miscible when the HPMC content is more than 50% in the blend. The change in temperature had no significant effect on the miscibility of HPMC/Pullulan blends. The semimiscibility is confirmed by ultrasonic velocity, density, and refractometric methods. The specific intermolecular interactions of hydrogen bonding type of the blends were investigated by DSC and FTIR. The miscible compositions of HPMC/Pullulan blend showed improved thermal and mechanical properties. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Surface Characterizations of Spin-Coated Films of Ethylcellulose and Hydroxypropyl Methylcellulose Blends

Films of pure ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) polymers and EC/HPMC blends were prepared from solutions by spin coating where isopropyl alcohol (IPA), water, and IPA/water cosolvent were used as solvents. Surface structures of the films were investigated using optical microscopy, atomic force microscopy (AFM), and Raman mapping and spectroscopy. For the films prepared from EC/HPMC blend solutions using the IPA/water cosolvent, different domain structures such as islands or pits and phase separation between EC and HPMC were observed by optical microscopy and AFM. The nature of the polymer components on the surface of the films was identified by Raman mapping and spectroscopy. Experimental results also indicated that polymer composition, solvent, and temperature during spin coating had significant impacts on surface structures of the films.

Blends of hydroxypropyl methylcellulose and poly(1-vinylpyrrolidone- co-vinyl acetate): Miscibility and thermal stability

The miscibility, kinetic parameters, and mechanism associated with the thermal degradation of hydroxypropyl methylcellulose/poly(1-vinylpyrrolidone- co-vinyl acetate) (HPMC/P(VP- co-VAc)) blends, were analysed. The presence of only one glass transition temperature ( T g) in the blend, intermediate between those for the pure polymers, the shift of the bands in the region of 3430 cm −1 and the disappearance of the band at 1647 cm −1 from the infrared spectra, suggest miscibility between the components. The thermogravimetric curves associated with the temperature of maximum degradation rate ( T max) indicate a higher thermal stability for the blend with 30% HPMC and for the pure copolymer. This conclusion was supported by the activation energy ( E) values which increased to ca. 190 and 170 kJ mol −1 for the blend with 30% HPMC and the pure copolymer, respectively. The E-values for the studied systems suggested a degradation mechanism associated with a random scission of the chain. The FTIR spectra of the solid residues from the thermal degradation reaction of both systems suggest the formation of alcohol and unsaturated hydrocarbons as reaction products. For the HPMC system, CO 2, CO, aldehydes, alcohols and ethers were detected as volatile products. Volatile products such as, acetic acid, CO 2, CO and NH 3 were detected for P(VP- co-VAc).

Sustained release of acetaminophen from a heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers

This study examined the release of acetaminophen (APAP) from hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) matrices. The effect of pseudoephedrine (PE) as a co-active, HPMC:HPC ratio, polymer loading, pH of the dissolution media, and compression force on APAP release were studied. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and HPC were compressed into tablets at different compression forces. APAP release from the matrix tablets was not considerably influenced by changes in HPMC:HPC ratio or compression force. The rate of drug release was significantly affected by pH of the dissolution media, total polymer loading, and the presence of PE. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP. Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45. Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.4. The drug release data showed a good fit to the Power Law Model. The mechanism of drug release is consistent with a complex behavior. The results of the tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation mechanism.

Interactions in poly(ethylene oxide)–hydroxypropyl methylcellulose blends

Blends of poly(ethylene oxide) and hydroxypropyl methylcellulose in the form of free films are examined for evidence of specific polymer:polymer interactions. Such interactions might affect the drug release behaviour of compressed matrices incorporating these polymers. The effect of HPMC on the crystallisation of PEO during casting is investigated using differential scanning calorimetry (DSC) and wide-angle X-ray diffraction. Fourier transform infra-red (FT-IR) and Raman spectroscopies are used to examine the possibility of a complex between the two polymers. Thermodynamic interaction parameters are calculated for films cast from water and N,N-dimethylacetamide (DMAc) using the Flory–Huggins theory of mixing. The interaction parameter calculated is negative, indicating a miscible blend, and a hydrogen bonding interaction is detected. This hydrogen bonding is less likely to occur in films cast from water than in films cast from DMAc perhaps because residual water can shield the interaction sites. Finally, a transition involving a sharp reduction in heat capacity at high temperatures is reported. This transition is characterised using DSC and FT-IR and Raman spectroscopies, and is interpreted as a further complexing of the polymers.

Assessment of polymer-polymer interactions in blends of HPMC and film forming polymers by modulated temperature differential scanning calorimetry.

To assess the miscibility and phase behavior of binary blends of hydroxypropylmethyl cellulose (HPMC) with hydroxypropyl cellulose (HPC), methylcellulose (MC), and polyvinylpyrrolidone (PVP). Polymer-polymer miscibility was assessed by measurement of the glass transition temperature (Tg) and the width of the glass transition temperature (W-Tg), using modulated temperature differential scanning calorimetry (MTDSC). HPMC K4M/PVP and HPMC E5/MC blends were miscible as evidenced by a single, composition dependent, Tg throughout the entire composition range. HPMC/HPC blends were immiscible at all compositions. For the miscible blends, the variation in Tg with blend composition was compared to the values predicted by the Fox and Couchman-Karasz equations. At intermediate blend compositions, HPMC K4M/PVP blends exhibited negative deviations from ideal behavior. The Tg of the HPMC E5/MC blends was found to follow the Fox equation. The W-Tg measurements of the miscible blends gave evidence of phase separation at certain compositions. MTDSC was shown to be a useful technique in characterizing the interactions between some commonly used pharmaceutical polymers.

Sustained Release of Acetaminophen from Heterogeneous Matrix Tablets: Influence of Polymer Ratio, Polymer Loading, and Co-active on Drug Release

ABSTRACTThe aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 lb. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (≥ 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.