methylcellulose and hydroxyethylcellulose

This study focused on the development of novel coating formulations for stainless steel microneedles against influenza A virus. With in vitro studies, various viscosity enhancers and stabilizers were screened based on the hemagglutination activity of the vaccine, which was coated and dried onto a stainless steel chip at room temperature for 1 day. Following the long-term storage test, the hemagglutination activity and particle size of the vaccine, which was formulated with conventional or methylcellulose or hydroxyethyl cellulose and dried onto the microneedle, were monitored. Next, to evaluate the in vivo immunogenicity and protection effect of each dried vaccine formulation, mice were immunized by the antigen-coated microneedle, which had either the conventional or the proposed formulation. Two novel formulations were chosen in the preliminary screening, and in further evaluations, they exhibited a 20 % higher HA activity during storage for 3 months, and no aggregation was observed during storage after drying. In a mouse model, the microneedle with the novel formulation elicited a higher level of IgG and IgG2a was more prevalent in the IgG isotype profile. In addition, mice immunized with the HEC-coated microneedle survived with small weight loss (>90 %) against lethal challenge infection. Overall, the novel formulation hydroxyethyl cellulose preserved significantly higher HA activity during the production and storage of the microneedle as well as improved the in vivo immunogenicity of the vaccine.

Topics: Animals; Cellulose; Drug Stability; Female; Hemagglutination Tests; Immunoglobulin G; Influenza Vaccines; Injections, Intradermal; Methylcellulose; Mice; Needles; Stainless Steel; Vaccination; Viscosity

Incipient caries lesions on smooth surfaces may be subjected to toothbrushing, potentially leading to remineralization and/or abrasive wear. The interplay of dentifrice abrasivity and fluoride on this process is largely unknown and was investigated on three artificially created lesions with different mineral content/distribution. 120 bovine enamel specimens were randomly allocated to 12 groups (n = 10), resulting from the association of (1) lesion type [methylcellulose acid gel (MeC); carboxymethylcellulose solution (CMC); hydroxyethylcellulose gel (HEC)], (2) slurry abrasive level [low (REA 4/ RDA 69); high (REA 7/RDA 208)], and (3) fluoride concentration [0/275 ppm (14.5 mM) F as NaF]. After lesion creation, specimens were brushed in an automated brushing machine with the test slurries (50 strokes 2×/day). Specimens were kept in artificial saliva in between brushings and overnight. Enamel surface loss (SL) was determined by optical profilometry after lesion creation, 1, 3 and 5 days. Two enamel sections (from baseline and post-brushing areas) were obtained and analyzed microradiographically. Data were analyzed by analysis of variance and Tukey's tests (α = 5%). Brushing with high-abrasive slurry caused more SL than brushing with low-abrasive slurry. For MeC and CMC lesions, fluoride had a protective effect on SL from day 3 on. Furthermore, for MeC and CMC, there was a significant mineral gain in the remaining lesions except when brushed with high-abrasive slurries and 0 ppm F. For HEC, a significant mineral gain took place when low-abrasive slurry was used with fluoride. The tested lesions responded differently to the toothbrushing procedures. Both slurry fluoride content and abrasivity directly impacted SL and mineral gain of enamel caries lesions.

Topics: Animals; Carboxymethylcellulose Sodium; Cariostatic Agents; Cattle; Cellulose; Dental Caries; Dental Enamel; Dentifrices; Gels; Methylcellulose; Microradiography; Minerals; Protective Agents; Random Allocation; Saliva, Artificial; Sodium Fluoride; Tooth Abrasion; Tooth Remineralization; Toothbrushing

The preparation of thin composite layers has promising advantages in a variety of applications like transdermal, buccal, or sublingual patches. Within this model study the impact of the matrix material on the film forming properties of ibuprofen-matrix composite films is investigated. As matrix materials polystyrene, methyl cellulose, or hydroxyl-ethyl cellulose were used. The film properties were either varied by the preparation route, i.e., spin coating or drop casting, or via changes in the relative ratio of the ibuprofen and the matrix material. The resulting films were investigated via X-ray diffraction and atomic force microscope experiments. The results show that preferred (100) textures can be induced via spin coating with respect to the glass surface, while the drop casting results in a powder-like behavior. The morphologies of the films are strongly impacted by the ibuprofen amount rather than the preparation method. A comparison of the various matrix materials in terms of their impact on the dissolution properties show a two times faster zero order release from methyl cellulose matrix compared to a polystyrene matrix. The slowest rate was observed within the hydroxyl ethyl cellulose as the active pharmaceutical ingredients (APIs) release is limited by diffusion through a swollen matrix. The investigation reveals that the ibuprofen crystallization and film formation is only little effected by the selected matrix material than that compared to the dissolution. A similar experimental approach using other matrix materials may therefore allow to find an optimized composite layer useful for a defined application.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Crystallization; Ibuprofen; Methylcellulose; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Pharmaceutical Solutions; Surface Properties; X-Ray Diffraction

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery.

Topics: Cellulose; Diltiazem; Drug Chronotherapy; Drug Delivery Systems; Ethylene Glycols; Humans; Hypromellose Derivatives; Kinetics; Methylcellulose; Pectins; Polymers; Tablets

The present study investigated the effects of fluoride (F) concentration, lesion baseline severity (ΔZ(base)) and mineral distribution on lesion progression. Artificial caries lesions were created using three protocols [methylcellulose acid gel (MeC), hydroxyethylcellulose acid gel (HEC), carboxymethylcellulose acid solution (CMC)] and with low and high ΔZ(base) groups by varying demineralization times within protocols. Subsequently, lesions were immersed in a demineralizing solution for 24 h in the presence of 0, 1, 2 or 5 ppm F. Changes in mineral distribution characteristics of caries lesions were studied using transverse microradiography. At baseline, the protocols yielded lesions with three distinctly different mineral distributions. Secondary demineralization revealed differences in F response between and within lesion types. In general, lowΔZ lesions were more responsive to F than highΔZ lesions. LowΔZ MeC lesions showed the greatest range of response among all lesions, whereas highΔZ HEC lesions were almost unaffected by F. Laminations were observed in the presence of F in all but highΔZ HEC and CMC lesions. Changes in mineral distribution effected by F were most pronounced in MeC lesions, with remineralization/mineral redeposition in the original lesion body at the expense of sound enamel beyond the original lesion in a dose-response manner. Both ΔZ(base) and lesion mineral distribution directly impact the F response and the extent of secondary demineralization of caries lesions. Further studies - in situ and on natural white spot lesions - are required to better mimic in vivo caries under laboratory conditions.

Topics: Acetic Acid; Animals; Apatites; Calcium Fluoride; Calcium Phosphates; Carboxymethylcellulose Sodium; Cariostatic Agents; Cattle; Cellulose; Dental Enamel; Disease Progression; Dose-Response Relationship, Drug; Durapatite; Fluorides; Hydrogen-Ion Concentration; Lactic Acid; Methylcellulose; Microradiography; Minerals; Temperature; Time Factors; Tooth Demineralization; Tooth Remineralization

Disaccharides are, in general, the first choice as formulation compounds when freeze-drying microorganisms. Although polysaccharides and other biopolymers are considered too large to stabilise and interact with cell components in the same beneficial way as disaccharides, polymers have been reported to support cell survival. In the present study we compare the efficiency of sucrose and the polymers Ficoll, hydroxyethylcellulose, hydroxypropylmethylcellulose and polyvinylalcohol to support the survival of three bacterial strains during freeze drying. The initial osmotic conditions were adjusted to be similar for all formulations. Formulation characterisation was used to interpret the impact that different compound properties had on cell survival.. Despite differences in molecular size, both sucrose and the sucrose-based polymer Ficoll supported cell survival after freeze drying equally well. All formulations became amorphous upon dehydration. Scanning electron microscopy and X-ray diffraction data showed that the discerned differences in structure of the dry formulations had little impact on the survival rates. The capability of the polymers to support cell survival correlated with the surface activity of the polymers in a similar way for all investigated bacterial strains.. Polymer-based formulations can support cell survival as effectively as disaccharides if formulation properties of importance for maintaining cell viability are identified and controlled.

Topics: Arthrobacter; Calorimetry, Differential Scanning; Cellulose; Colony Count, Microbial; Cryoprotective Agents; Ficoll; Freeze Drying; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Methylcellulose; Microbial Viability; Microscopy, Electron, Scanning; Polyvinyl Alcohol; Pseudomonas putida; Sphingomonas; Structure-Activity Relationship; Sucrose; Surface Tension; Surface-Active Agents; Transition Temperature; X-Ray Diffraction

A swelling-controlled mechanism, based on the simple fitting of drug release data to a power law, is frequently invoked to explain deviations from Fickian diffusion. Therefore, the purpose of this work was to evaluate whether such a mechanism is possible in the case of compressed hydrophilic matrices made of cellulose ethers, using parameters that were independently obtained, either in Part I (Ferrero et al.,) or in the present study. The derivatives used were hydroxypropyl methyl celluloses, hydroxyethyl celluloses and hydroxypropyl celluloses of varying molecular mass. We investigated polymer chain relaxation (by mechanical testing and oscillatory rheology), the release characteristics of the model drug sodium salicylate, as well as the swelling behavior of the compressed tablets (front movements and water uptake). Assessment of a possible swelling-controlled release (relaxation-controlled, penetrant-activated) mechanism was based on the use of the Deborah number, De, and that of the swelling interface number, Sw. Two extreme polymer fractions were considered for the evaluation of De and Sw, namely those fractions that were assumed to be present at the swelling front and at the eroding front. Analysis of drug release data using the Korsmeyer-Peppas model resulted in diffusional exponent n values that were consistently greater than 0.44 (for the cylindrical geometry used here), which could thus indicate anomalous (coupled diffusion-relaxation) drug transport behavior. However, from the observed De values<<1 (at both fronts), which are indicative of water Fickian diffusion in the rubbery polymer matrix, and the Sw values>>1 (at the swelling front), which correspond to drug Fickian diffusion, we infer that a swelling-controlled drug release mechanism should be dismissed for such water-soluble hydrophilic cellulose ethers, i.e. polymer chain relaxation is not the rate-limiting step in the drug release process from this type of hydrophilic polymer. In fact, Sw values close to unity were calculated for the erosion front, but this is not a sufficient criterion for a swelling-controlled release mechanism. In addition, the dimensionless numbers calculated for the erosion front should be considered cautiously and conservatively since relaxation of the macromolecules is very unlikely to still occur when the latter are in the process of detaching from the polymer matrix. In addition, it was experimentally confirmed from the front positions that erosion is the pheno

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Drug Carriers; Drug Compounding; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Biological; Molecular Conformation; Sodium Salicylate; Solubility; Tablets; Transition Temperature; Viscosity; Water

In this paper, the effect of anhydrous-monohydrate process-induced transformation of theophylline was examined in microcapsules produced by in situ gelation method using sodium alginate, hydroxypropylmethylcellulose and hydroxyethylcellulose. Films produced from gel were applied to characterize the changes by NIR spectroscopy, X-ray, DSC method and stereomicroscopy because it is easier to study that in films in the case of gel systems used in situ gelation process. The properties of end-product are influenced by the swelling ability, equilibrium water uptake, release profile and encapsulation efficiency. Water penetration and drug release were evaluated by Davidson-Peppas and Korsmeyer-Peppas models. The ex tempore formed monohydrate crystals were smaller and built into the matrix structure in a greater extent. Increased drug release, matrix erosion and diffuse reflectance values at 1470 and 1950 nm were observed added theophylline later into the gel because of developing a denser structure.

Topics: Alginates; Bronchodilator Agents; Capsules; Cellulose; Crystallization; Gels; Glucuronic Acid; Hexuronic Acids; Hypromellose Derivatives; Methylcellulose; Models, Chemical; Polymers; Theophylline; Water

Vaginal gels may act as physical barriers to HIV during sexual transmission. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within the lower female reproductive tract. In cases where a topical gel has previously been applied to the vaginal epithelium, virions must move through gel layers before reaching vulnerable tissue. This additional barrier could affect the functioning of anti-HIV microbicide gels and placebos. To better understand HIV transport in gels, we: (1) quantified diffusion coefficients of HIV virions within semi-solid delivery vehicles; and (2) tested the barrier functioning of thin gel layers in a Transwell system. Two gels used as placebos in microbicides clinical trials, hydroxyethyl cellulose (HEC) and methylcellulose (MC), were found to hinder HIV transport in vitro. The diffusion coefficients for HIV virions in undiluted HEC and MC were 4±2 x 10⁻¹² and 7±1 x 10⁻¹² cm²/s, respectively. These are almost 10,000 times lower than the diffusion coefficient for HIV in water. Substantial gel dilution (80%:diluent/gel, v/v) was required before diffusion coefficients rose to even two orders of magnitude lower than those in water. In the Transwell system, gel layers of approximately 150-μm thickness reduced HIV transport. There was a log reduction in the amount of HIV that had breached the Transwell membrane after 0-, 4-, and 8-h incubations. The ability of a gel to function as a physical barrier to HIV transport from semen to tissue will also depend on its distribution over the epithelium and effects of dilution by vaginal fluids or semen. Results here can serve as a baseline for future design of products that act as barriers to HIV transmission. The potential barrier function of placebo gels should be considered in the design and interpretation of microbicides clinical trials.

Topics: Administration, Intravaginal; Anti-HIV Agents; Anti-Infective Agents; Cellulose; Diffusion; Drug Design; Female; Gels; HIV Infections; HIV-1; Humans; Male; Methylcellulose; Vagina; Vaginal Creams, Foams, and Jellies

The European Pharmacopoeia (Ph. Eur.) monographs for the water-soluble cellulose ethers require viscosity determination, either in the "Tests" section or in the non-mandatory "Functionality-related characteristics" section. Although the derivatives are chemically closely related and used for similar applications, the viscosity tests strongly differ. Some monographs generically speak of the rotating viscometer method (2.2.10) and a fixed shear rate (e.g. 10 s-1), which would necessitate an absolute measuring system, while others recommend the capillary viscometer method for product grades of less than 600 mPa∙s and the rotating viscometer method and given operating conditions for grades of higher nominal viscosity. Viscometer methods also differ between the United States Pharmacopeia/National Formulary (USP/NF) and the Japanese Pharmacopoeia (JP) monographs. In addition, for some cellulose ethers the tests sometimes diverge from one pharmacopoeia to the other, although the three compendiums are in a harmonisation process. But the main issue is that the viscometer methods originally employed by the product manufacturers are often not those described in the corresponding monographs and generally vary from one manufacturer to the other. The aim of this study was therefore to investigate whether such a situation could invalidate the present pharmacopoeial requirements. 2 per cent solutions of several viscosity grades of hydroxyethylcellulose, hypromellose and methylcellulose were prepared and their (apparent) viscosity determined using both relative and absolute viscometer methods. The viscometer method used not only affects the measured viscosity but experimental values generally do not correspond to the product nominal viscosities. It emerges that, in contrast to Newtonian solutions (i.e. those of grades of up to ca. 50 mPa∙s nominal viscosity), some of the viscometer methods currently specified in the monographs are not able unambiguously to characterise the grades exhibiting non-Newtonian behaviour. It is also concluded that, unless the various manufacturers redefine their product viscosity grades using a single compendial test, two strategies could be adopted, both based on the operating conditions specified in the labeling (i.e those of the manufacturer), the test appearing either in the mandatory section if this is acceptable to the pharmacopoeia (like in some USP/NF monographs) or, for the Ph. Eur., in the "Functionality-related characteristics" sectio

Topics: Cellulose; Ethers; Hypromellose Derivatives; Methylcellulose; Temperature; Viscosity

The present study was aimed to prepare and evaluate buccoadhesive films of miconazole nitrate (MCZ). The films based on chitosan were prepared by solvent casting method using L(9) orthogonal array design to release the drug above its minimum inhibitory concentration (MIC) for a prolonged period of time so as to reduce its frequency of administration. As per the experimental design, guar gum, HPMC K15M and HEC were added at three different levels to control the drug release. Films showed smooth, uniform and non-sticky surface with good flexibility and folding endurance. Thickness and weight-variation data showed no significant difference among the batches, indicating that the polymeric blend possessed a good film forming ability and its desired properties could easily be achieved by varying the composition of the casting solution. Films composed of chitosan with guar gum appeared to be tougher; comparatively more bioadhesive in vitro, resided to an appropriate time interval and swelled at a more reasonable rate than those containing HPMC and HEC, suggesting the superiority of guar gum over other polymers. In vitro drug release studies conducted on all batches and microbiological studies done on the statistically optimized formulation demonstrated that the films had ability to sustain the drug concentration above its MIC for 6 hrs, despite the incorporation of a smaller dose (2.5 mg/cm(2) of the film). Films, except CF2 and CF3, followed Fickian diffusion of release mechanism. FT-IR spectra revealed no interactions between the drug and polymers.

Topics: Adhesiveness; Administration, Buccal; Analysis of Variance; Biological Availability; Candida albicans; Cell Proliferation; Cellulose; Chemistry, Pharmaceutical; Chitosan; Delayed-Action Preparations; Drug Design; Drug Stability; Elasticity; Excipients; Galactans; Hypromellose Derivatives; Kinetics; Mannans; Methylcellulose; Miconazole; Microscopy, Electron, Scanning; Models, Theoretical; Plant Gums; Spectroscopy, Fourier Transform Infrared; Surface Properties; Temperature; Tensile Strength; Water

The purpose of this study was to develop poloxamer-based in situ gelling formulations of ciprofloxacin hydrochloride (HCl) aiming at prolonging corneal contact time, controlling drug release, enhancing ocular bioavailability, and increasing patient compliance. The in situ forming gels were prepared using different concentrations of poloxamer 407 (P407) and poloxamer 188 (P188). Mucoadhesives such as hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were added to the formulations to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their in vitro drug release, sol-gel transition temperature, rheological behavior, and mucoadhesion force. The in vivo antimicrobial efficacy of selected ciprofloxacin HCl in situ gelling formulations was studied on infected rabbit's eyes and compared with that of the marketed conventional eye drops. The gelation temperature of the prepared formulations ranged from 28.00 to 34.03 degrees C. Increasing the concentrations of P407, HPMC, and HEC increased the viscosity and mucoadhesion force of the preparations and decreased the in vitro drug release. Ciprofloxacin HCl in situ forming gel formulae composed of P407/P188/HPMC (18/13/1.5%, wt/wt), and P407/P188/HEC (18/13/0.5%, wt/wt) showed optimum release and mucoadhesion properties and improved ocular bioavailability as evidenced by an enhanced therapeutic response compared with the marketed conventional eye drops.

Topics: Adhesiveness; Animals; Anti-Infective Agents; Biological Availability; Cellulose; Ciprofloxacin; Conjunctivitis, Bacterial; Delayed-Action Preparations; Disease Models, Animal; Excipients; Gels; Hypromellose Derivatives; Methylcellulose; Patient Compliance; Poloxamer; Rabbits; Rheology; Transition Temperature; Viscosity

The objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethyl cellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23 factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.

Topics: Biological Availability; Buffers; Cellulose; Chemistry, Pharmaceutical; Citrates; Cyclooxygenase 2 Inhibitors; Dimethylformamide; Drug Carriers; Drug Compounding; Emulsifying Agents; Excipients; Geriatrics; Mannitol; Meloxicam; Methylcellulose; Polyethylene Glycols; Polysorbates; Sodium Citrate; Solubility; Suspensions; Thiazines; Thiazoles

Cellulose ethers have been increasingly used in the formulation of controlled release dosage forms; among them, compressed hydrophilic matrices for the oral route of administration are of special importance. Much interest has also been expressed in the study of the drug release mechanism from such swellable systems, in particular, in trying to explain deviations from Fickian diffusion. Thus, swelling-controlled transport is often invoked without any rationale. It is the purpose of the present work to provide independently determined diffusivity data for elucidating the drug release mechanism from the water-soluble cellulose derivatives. In the first part of this work, pulsed-field-gradient spin-echo nuclear magnetic resonance (PFG-SE NMR) was used to investigate the self-diffusion of the model solute sodium salicylate and, incidentally, that of water, in hydrogels made of hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC) and hydroxypropylcellulose (HPC) of varying polymer weight fraction and molecular weight in D2O. In parallel, the extent of bound water in the gels was determined using differential scanning calorimetry (DSC), and the presence of liquid crystals in the gels was examined by polarized light microscopy, as these are the structural factors capable of affecting drug diffusion. Solute diffusivity was not significantly affected by the substitution type of the cellulose ether, and an exponential polymer weight fraction dependence of the solute's self-diffusion coefficient was observed, ascertaining the validity of the free-volume theory, with extrapolated self-diffusion coefficient values similar to those in pure solvent. This also indicates that diffusion also takes place in the so-called bound water (which represents about 40% of the hydrogel weight). This questions the existence of thermodynamically different classes of water. Slightly reduced solute diffusion was measured in the HPC hydrogel of the highest polymer concentration (45 wt.%) where a liquid crystalline mesophase was observed. This structural factor could be of importance, especially in consideration of hydrogels of higher polymer fractions. The polymer molar mass (viscosity grade) of the cellulose ethers also did not affect solute self-diffusivity. The polymer matrix displayed the same retarding effect at equal weight fraction. This confirms that solute molecules can only diffuse in the void space occupied by the solvent. Solute self-diffusivity is dictated by the

Topics: Calorimetry, Differential Scanning; Cellulose; Diffusion; Hydrogels; Hypromellose Derivatives; Magnetic Resonance Spectroscopy; Methylcellulose; Microscopy, Polarization; Polymers; Sodium Salicylate; Water

Detailed knowledge based on new developments, especially in analytical techniques, is needed for characterizing polymer excipients. Inverse gas chromatography (IGC) is a useful method for investigating polymer surfaces in terms of thermodynamic parameters. The aim of our work was to study the correlation between polymer surface properties determined with IGC and the mechanisms of release of water-soluble pentoxifylline and vancomycin hydrochloride from cellulose ether matrices. Tablets were made of hydroxypropyl (HPC), hydroxyethyl (HEC) or hydroxypropylmethyl (HPMC) cellulose and contained 25% of drug. Differences in dispersive component of the surface free energy for these polymers were relatively small and ranged from 26 to 33mN/m. However, polar properties, expressed as specific component of the enthalpy of adsorption and as acid-base properties show larger differences between the polymers and demonstrate their relative polarity in the order HEC>HPMC>HPC, which correlates well with water sorption on bulky polymers and with the swelling degree of polymer matrices. The release of pentoxifylline and vancomycin from HPC is governed mainly by Fickian diffusion, whereas from HEC the relaxation of polymer chains is important too. The analysis of the release profiles in the light of Peppas-Sahlin model lead to the conclusion that the surface properties of the cellulose ethers influence the interactions with water and the release mechanisms of the drug. It was found out, that data obtained by IGC enable rapid inference about the behaviour of polymers in water and the release of water-soluble drugs.

Topics: Cellulose; Chromatography, Gas; Delayed-Action Preparations; Diffusion; Hypromellose Derivatives; Kinetics; Methylcellulose; Pentoxifylline; Polymers; Reproducibility of Results; Solubility; Surface Properties; Tablets; Thermodynamics; Vancomycin; Water

The novel approach described allows to characterise the surfactant-polymer interaction under several sodium dodecyl sulphate (SDS) concentrations (0-20 mM) using size exclusion chromatography (SEC) with online multi-angle light scattering (MALS) and refractometric (RI) detection. Three different cellulose derivatives, hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC) and hydroxyethyl cellulose (HEC), have been studied in solution containing 10 mM NaCl and various concentrations of sodium dodecyl sulphate. It is shown that this approach is well suited for successful application of both Hummel-Dreyer and multi-component light scattering principles and yields reliable molecular masses of both the polymer complex and the polymer itself within the complex, the amount of surfactant bound into the complex as well as appropriate values of the refractive index increment (dn/dc)micro, of both the complex and the polymer in question. The more hydrophobic derivatives HPC and HPMC adsorbed significantly more SDS than HEC. The inter-chain interactions close to critical aggregation concentration (cac) were clearly seen for HPC and HPMC as an almost two-fold average increase in polymer molecular mass contained in the complex.

Topics: Cellulose; Chromatography, Gel; Hypromellose Derivatives; Light; Methylcellulose; Online Systems; Refractometry; Scattering, Radiation; Sodium Dodecyl Sulfate; Solutions

The paper is concerned with the formulation of the antihistamine cetirizine into hydrogels. The cellulose derivatives hydroxyethylcellulose (HEC) and methylcellulose (MC) were employed to prepare hydrogels. As auxiliary substances from the group of humectants are indispensable components of hydrogels, the paper examines their effect (glycerol--GL, propylene glycol--PG, and sorbitol--SO) on the rheological properties and pharmaceutical availability of cetirizine in its formulation into hyrogel. The obtained results show that from the viewpoint of dermal administration for cetirizine at this stage of research hydrogels of the following composition are optimal: 3% HEC + 15% GL and 2.5% MC + 10% SO.

Topics: Cellulose; Cetirizine; Chemistry, Pharmaceutical; Glycerol; Histamine H1 Antagonists; Hydrogels; Methylcellulose; Pharmaceutic Aids; Propylene Glycol; Rheology; Sorbitol

The purposes of this study were to establish a quantitative method for evaluating rabbit tear film status and investigate the efficacy of artificial tear preparations through ocular surface bathing or eye drop application.. The rabbit tear film was evaluated using a noninvasive specular reflection video recording system. The appearance of a tear break area (TBA) on the tear film images (7.4 mm2/mm) after 30 seconds of eye opening was quantified by image analysis. To induce disruption of the rabbit tear film, the ocular surface was challenged for 60 minutes with 1 ppm hypochloric acid (HOCl). Immediately after irrigation, artificial tear preparations composed of viscosity agents sodium hyaluronate (SH), hydroxypropylmethycellulose (HPMC), hydroxyethylcellulose (HEC), or chondroitin sulfate (CS) were applied to the rabbit eye through ocular surface bathing or eye drop application, and the recovery of the disrupted tear film was compared for each preparation.. A dramatic increase in TBA was observed immediately after the ocular surface was challenged with HOCl, and it returned to the initial level after 6 hours. Immediately after ocular surface bathing and eye drop application, a dramatic recovery of TBA was observed in all the test solution-treated eyes. One hour after treatments, prolonged amelioration of the tear film instability was observed after ocular surface bathing, but not by eye drop application, with the artificial tear preparations composed of HPMC or SH.. Ocular surface bathing with artificial tear preparations composed of a suitable viscosity agents could be useful in managing tear film instability.

Topics: Animals; Cellulose; Chondroitin Sulfates; Disease Models, Animal; Dry Eye Syndromes; Hyaluronic Acid; Hypochlorous Acid; Hypromellose Derivatives; Methylcellulose; Ophthalmic Solutions; Rabbits; Tears; Viscosity

Mucoadhesive patches containing 10mg miconazole nitrate were evaluated. The patches were prepared with ionic polymers, sodium carboxymethyl cellulose (SCMC) and chitosan, or non-ionic polymers, polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC) and hydroxypropylmethyl cellulose (HPMC). Convenient bioadhesion, acceptable elasticity, swelling and surface pH were obtained. Patches exhibited sustained release over more than 5h and the addition of polyvinyl pyrrolidone (PVP) generally enhanced the release rate. Optimum release behaviour was shown with patches containing 10% w/v PVA and 5% w/v PVP. Study of the in vivo release from this formulation revealed uniform and effective salivary levels with adequate comfort and compliance during at least 6h. On the contrary, in vivo release of the commercial oral gel product resulted in a burst and transient release of miconazole, which diminished sharply after the first hour of application. Storage of these patches for 6 months did not affect the elastic properties, however, enhanced release rates were observed due to marked changes in the crystal habit of the drug.

Topics: Adhesiveness; Adjuvants, Pharmaceutic; Administration, Buccal; Administration, Oral; Adult; Antifungal Agents; Carboxymethylcellulose Sodium; Cellulose; Chemistry, Pharmaceutical; Chitin; Chitosan; Cross-Over Studies; Delayed-Action Preparations; Drug Stability; Female; Humans; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Miconazole; Middle Aged; Mouth Mucosa; Polyvinyl Alcohol; Time Factors

The effect of different grades of hydroxyethyl cellulose (HEC) and hydroxypropyl methllcellulose (HPMC) on the film-formation and taste-masking ability for ibuprofen granules was evaluated. Three batches of coated ibuprofen granules were prepared using a roto-granulator, each with a different coating composition. Two grades of HEC [MW300,000 (H) and MW90,000 (L)] were combined with three different grades of HPMC [MW 11,000 (L), MW 25,000 (M) and MW 35,000 (H)] to prepare the coating solutions. Mechanical strength and physical properties of the polymer films were evaluated. Films made from HPMC (L)/HEC (H), HPMC (M)/HEC (H), and HPMC (H)/HEC (H) were stronger and more flexible than the HPMC (L) HEC (L) films. The assay, dissolution, particle size distribution, and environmental scanning electron microscopy (ESEM) data of the three batches of the coated ibuprofen granules were similar.

Topics: Cellulose; Drug Compounding; Excipients; Hypromellose Derivatives; Ibuprofen; Methylcellulose; Microscopy, Electron, Scanning; Molecular Weight; Particle Size; Pharmaceutical Preparations; Polymers; Solubility; Tablets; Taste; Water

Gel formulations of ciprofloxacin hydrochloride (CPH) were prepared with bioadhesive polymers such as hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC) and methylcellulose (MC). They were administered into the nasal cavity of rabbits. A nasal aqueous suspension of CPH with glycerol was also applied. In addition, the effect of Tween 80 as penetration enhancer was examined. The agar plate diffusion technique was applied for the assay of CPH. The results were compared with oral and intravenous administrations. The bioavailability of the CPH gel formulation prepared with HPMC was almost identical to that of the oral route. Other nasal formulations with HEC and MC had bioavailabilities lower than oral preparations. The relative bioavailabilities for the formulation containing HEC and MC were 48.7 and 45.54%, respectively. To increase the bioavailabilities, 1% (w/w) of Tween 80 was added. The bioavailability of these gel formulations increased to 63.54 and 55.72%, respectively. Experiments carried out on rabbits showed that the nasal administration of CPH bioadhesive gel formulation containing HPMC may be an alternative to the oral route.

Topics: Administration, Oral; Animals; Anti-Infective Agents; Biological Availability; Calibration; Cellulose; Ciprofloxacin; Excipients; Female; Injections, Intravenous; Lactose; Male; Methylcellulose; Oxazines; Pharmaceutic Aids; Rabbits

In the course of the drug form development of heptacaine potential local anaesthetic, the influence of auxiliary substances on the heptacaine release and its local anaesthetic effect was studied. The obtained results show that the following auxiliary substances are optimal: a) 0.3-1.2% solution hydroxypropylmethyl cellulose for 0.025% eye drops, which have the fastest onset of the local anaesthetic effect in the hamster's eye, b) hydroxyethyl cellulose containing 0.5% heptacaine and 10% glycerol or propylene glycol for hydrogels, c) cocoa oil without and with Dimodan S for suppositories.

Topics: Anesthesia, Local; Anesthetics, Local; Animals; Cellulose; Cricetinae; Delayed-Action Preparations; Hypromellose Derivatives; Methylcellulose; Ophthalmic Solutions; Piperidines; Solutions; Time Factors

The influence of viscolysers on the precorneal residence of a fluorescent tracer was determined, using slit lamp fluorophotometry. The solution acceptability was evaluated by the volunteers by answering a standard questionnaire. The relationship between precorneal retention of viscous eye drops, discomfort and tear fluid composition after instillation of various cellulosic solutions was examined. Irritating hydroxypropylcellulose solution increases the total protein concentration of tears, without change in the ratio of lysozyme to total protein.

Topics: Cellulose; Cornea; Eye Proteins; Fluorescein; Fluoresceins; Fluorophotometry; Humans; Hypromellose Derivatives; Methylcellulose; Ophthalmic Solutions; Osmolar Concentration; Surface Tension; Tears; Viscosity

The glass-rubber transition temperatures (Tg) of several cellulosic polymers [hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC)] have been examined using dynamic mechanical analysis (DMA). The melting temperatures of the above polymers were examined using a hot stage melting point apparatus. The primary Tg of three different grades of HPMC (3, 6, and 15 cps) were determined to be 160, 170, and 175 degrees C, respectively. The primary Tg of the HEC film was determined as 120 degrees C. The HPC film did not indicate a primary Tg. These cellulosic polymers also displayed secondary transitions. Hot stage melting of HPMC and HPC was observed at 225 to 254 degrees C and 190 to 195 degrees C, respectively. The HEC powder did not exhibit a melting temperature, but became darker at temperatures greater than 150 degrees C.

Topics: Cellulose; Chemical Phenomena; Chemistry, Physical; Glass; Hypromellose Derivatives; Methylcellulose; Polymers; Rubber; Temperature

The electrophoretic separation of nucleic acids, including small DNA fragments in the range 50-1000 bp, is presently carried out in polyacrylamide gels or in gels containing high concentrations of agarose. We have developed an alternative gel matrix composition which is inexpensive, nontoxic, easy to prepare, and highly transparent to visible and uv light. The composition combines a soluble nonionic polysaccharide such as hydroxyethylcellulose, methylcellulose, or galactomannan with a minimum but sufficient concentration of agarose to form a gel which immobilizes the "liquid phase sieve." These mixtures do not replace polyacrylamide for resolving fragments smaller than approximately 75 nucleotides. However, the new gels show DNA fragment resolution (band separation versus distance traveled) and optical clarity superior to those of conventional agarose.

Topics: Carbohydrates; Cellulose; DNA; Electrophoresis, Agar Gel; Galactose; Mannans; Methylcellulose; Polymers

Topics: Cellulose; Cellulose, Oxidized; Chemical Phenomena; Chemistry, Physical; Chromatography, Gel; Hypromellose Derivatives; Methylcellulose; Structure-Activity Relationship; Viscosity

The use of sufficiently high concentrations of polyvinylpyrrolidone (PVP), hydroxyethyl cellulose (HEC) and methyl cellulose (MC) in tablet formulations leads to depot preparations of the prolonged- or sustained-release type. Having swollen up with the dissolution medium, the tablets form a hydrated matrix from which the active agent diffuses for a considerable time at constant speed. The verification of the bioavailability of chlorpromazine from PVP-, MC- and HEC-containing tablets and of a macromoleculefree standard preparation on rabbits showed considerable differences among the plasma curves. With reference to the standard preparation, the cellulose-containing preparations have a relative bioavailability of 38.8 and 45.7%, respectively. The constancy of the plasma level values for almost 8 h is remarkable. The plasma level profile of these formulations corresponds to that of a depot form of the sustained-release type.

Topics: Animals; Biopharmaceutics; Biotransformation; Cellulose; Chlorpromazine; Kinetics; Macromolecular Substances; Methylcellulose; Povidone; Rabbits

Topics: Cellulose; Conjunctiva; Drug Combinations; Humans; Methylcellulose; Ophthalmic Solutions; Pilocarpine; Viscosity