Biomedical subjects

C Alvarez-Lorenzo

Publications and source records attributed to C Alvarez-Lorenzo.

At least 19 recordsLinked to original sources

PubMed2006

Estradiol sustained release from high affinity cyclodextrin hydrogels.

Hydrogels for loading estradiol and controlling its release were prepared cross-linking various cyclodextrins with ethyleneglycol diglycidylether. To select the more adequate cyclodextrins, estradiol solubility diagrams in water with beta-cyclodextrin (betaCD), methyl-beta-cyclodextrin (MbetaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), and sulfobutyl-beta-cyclodextrin (SBbetaCD) were made in absence and presence of hydroxypropyl methylcellulose (HPMC) applying or not autoclaving. Although all cyclodextrins showed enough complexation capability, the low solubility of betaCD and the high anionic character of SBbetaCD hindered the cross-linking process, and these cyclodextrins were discarded for preparing hydrogels. Hydrogels prepared with MbetaCD (20%, 25%) or HPbetaCD (20%, 25%, and 30%), with or without HPMC 0.25%, absorbed 4-10 times their weight in water and loaded up to 24 mg estradiol per gram, which is 500 times greater than the amount of drug that can be dissolved in their aqueous phase. Positive linear correlation was found between the stability constant and the network/water partition coefficients of drug. The hydrogels sustained the release up to one week; the affinity of estradiol for the cyclodextrin units controlling the process, as shown by the negative correlation with the release rate constants. These results highlight the potential of cyclodextrin complexation for the development of hydrogels useful in loading hydrophobic drugs and controlling their release.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2005

Preparation of chitosan beads by simultaneous cross-linking/insolubilisation in basic pH. Rheological optimisation and drug loading/release behaviour.

A one-step procedure to prepare chitosan beads by simultaneous cross-linking with glutaraldehyde and insolubilisation in 1.5 M NaOH solution has been developed. The optimisation of the procedure was carried out by monitoring the evolution of the loss and storage moduli of chitosan solutions (1.5% (w/v), in acetic acid 0.2 M) in the presence of different proportions of glutaraldehyde. Increasing the chitosan molecular weight, glutaraldehyde concentration and/or process temperature from 20 to 37 degrees C, a reduction of time to reach the gel point was observed. The diameter of freshly prepared swollen beads was 3.2+/-0.4 mm and, after drying 0.48+/-0.18 mm. Swollen or previously dried beads were loaded with metronidazole by immersion in 0.1% (w/v), drug solution in a phosphate buffer pH 7.5, purified water, 0.2 M acetic acid or 0.1 M HCl. Beads synthesised at 37 degrees C experimented faster swelling than the ones prepared at 20 degrees C and even disintegrated in acetic acid. The amounts of metronidazole loaded (ranging from 1 to 286 mg/g dried beads) increased with swelling capacity of beads. The release studies carried out in 0.1 M HCl indicated that, regardless of the medium used to load the beads, all of them released the dose in less than 30 min. In summary, applying this one-step procedure and choosing the adequate glutaraldehyde proportion, it is possible to obtain particles of chitosan cross-linked with itself, which exhibit pH-sensitive swelling and which are able to release all the drug quickly into an acidic environment such as the stomach. The results obtained also highlight the importance of the pH of the medium for modulating the amount of drug loaded (it is remarkably greater at lower pHs) and the influence of temperature at which the beads are prepared on their tendency to disintegrate.

Chitosan↗

PubMed2005

Structural properties of biodegradable polyesters and rheological behaviour of their dispersions and films.

This paper focuses on the dependence of the rheological properties of PLA-PEG and PLGA dispersions and films on the polymer structural properties, in order to obtain useful information to predict and explain the performance of polyester films as drug-delivery systems. In this study, one PLA-PEG and three PLGA polymers of different molecular mass were synthesized and characterized by NMR, GPC, DSC and TGA-FT-IR. To characterize the viscoelastic behaviour of concentrated solutions in dichloromethane and of the films obtained by a solvent-casting technique, oscillatory shear rheometry was used. The polymer dispersions showed a characteristic Newtonian viscous behaviour, but with different consistency index depending on the nature of the polymer. Freshly prepared, PLGA and PLA-PEG films had elastic modulus (G') greater than viscous modulus (G"). The decrease in both moduli caused by an increase in temperature from 25 to 37 degrees C was especially marked for the polymers with T(g) below or around 25 degrees C (PLGA 27 kDa and PLA-PEG 27 kDa). After being immersed in pH 7.4 aqueous solution for one week, PLGA films showed a significant increase in both G' and G", due to the promotion of polymer-polymer interactions in a non-solvent medium. In contrast, the PLA-PEG film became softer and more hydrated, due to the amphiphilic character of the polymer. The water taken up by the film acted as a plasticizer and induced the softening of the system. These results suggest that the presence of PEG chains exerts a strong influence on the mechanical properties of polyesters films and, possibly, the performance as coating or matrices of drug-delivery systems.

Biodegradation, Environmental↗

PubMed2004

Glass transitions and viscoelastic properties of carbopol and noveon compacts.

Glass transitions of five varieties of Carbopol (acrylic acid polymers cross-linked with allyl sucrose or allyl pentaerythritol) and two varieties of Noveon (calcium salts of acrylic acid polymer cross-linked with divinylglycol) differing in cross-linking density and nature and content in residual solvents, were analysed (as compressed probes) by differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (MTDSC), and oscillatory rheometry. All carbopol compacts showed a main glass transition, at a temperature between 130 and 140 degrees C, Tg, independently of their cross-linking degree and molecular weight. Additionally two batches of Carbopol 971P, which had greater contents in residual solvents, also presented a secondary transition at 65-70 degrees C. Sorption of water during storage of carbopol compacts at different relative humidity environments caused the Tg to strongly decrease. Compacts stored at 97.5% relative humidity have Tg below 0 degrees C and behave, at room temperature, as flexible hydrogels. The Gordon-Taylor/Kelley-Bueche equation only fit the dependence of Tg on water content well for carbopol compacts containing less than 15% water. The plasticizing effect of water was clearly evidenced in the considerable decrease in the storage and loss moduli of the compacts. Although the energy associated to the glass transitions of carbopol polymers, 0.40-0.50 Jg(-1) degrees C(-1), is high enough to be clearly detected by DSC, in some cases the evaporation of residual solvents may make it difficult to observe the Tg. This inconvenience is overcome using MTDSC or oscillatory rheometry. The decrease in Tg of carbopol caused by water sorption when compacts were stored at 97.5% R.H. explains why their loss (G") and storage (G') moduli at room temperature decreased four orders of magnitude. In contrast, in noveon varieties, calcium ions act as ionic cross-linkers of the carboxylic groups, providing rigid networks with much higher Tg, and storage and loss moduli. This explains that despite sorbing similar amounts of water to carbopol, the changes on the mechanical properties of noveon compacts were much less important (i.e., G' and G" decreased up to one order of magnitude).

Acrylic Resins↗

PubMed2004

Rheological properties of PLGA film-based implants: correlation with polymer degradation and SPf66 antimalaric synthetic peptide release.

This paper reports on the rheological properties of poly(D,L-lactic-co-glycolic acid) polymers (PLGA) dispersions used to form films and of the implants prepared by compression of SPf66 antimalaric peptide between several films, before application and during drug release. 25% PLGA (M(w)=48,000Da) dispersions in dichloromethane showed viscous Newtonian behaviour, being easy flowing and adaptable to the moulds. Evolution of viscoelastic properties, polymer molecular weight, and SPf66 release pattern from the implants immersed in various media was evaluated. Oscillatory shear test showed that freshly prepared implants have an elastic modulus, G', greater than the viscous modulus, G", being both practically independent of angular frequency. After 6 weeks immersion in a pH 7.4 phosphate buffer, G' and G" increased in almost one order of magnitude, despite of a significant polymer degradation. Polymer molecular weight decreased slowly during the first 10 days of immersion (a similar pattern was obtained at pHs 2 and 7.4) and then the degradation process accelerated (degradation index on day 7 equals to 0.89, and on day 14 equals to 16.5). SPf66 release profile followed a pattern similar to that of the polymer degradation index. These observations are explained in terms of changes in polymer structure and conformation that happen in the implant.

Absorbable Implants↗

PubMed2003

Poly(acrylic acid) microgels (carbopol 934)/surfactant interactions in aqueous media. Part I: nonionic surfactants.

The interaction between Tween 80 and Pluronic F-127 with carbopol in water was studied as a function of surfactant concentration. 0.25% carbopol microgels dispersions showed a continuous decrease in transmittance, viscosity and conductivity when surfactant concentration ranged from 0.01-0.02% to 0.50% Tween 80 or from 0.03-0.06% to 0.30% Pluronic F-127. These limit values can be considered as the critical association concentration and the saturation binding concentration, respectively. In this concentration range, a strong rise in pH (from 3.18 to 3.50) suggested that surfactant-polymer binding occurred mainly through a stoichiometric hydrogen-bonding interaction between the oxyethylene and carboxylic groups. In the presence of carbopol, the concentration of Tween 80 at the air/water interface decreases as the surfactant is adsorbed onto the polymer and drawn into the bulk solution. In contrast, the interaction with the polymer seems to change the conformation of the expanded chains of Pluronic F-127, making it easier for more molecules of surfactant to be at the interface and increasing the thickness of the interfacial surfactant layer. Fluorescence probes indicated that the carbopol network presents a more apolar medium than pure water, and the differences in the hydrophile-lipophile balance (HLB) of each surfactant were responsible for the lower I(I)/I(III) values obtained with Tween 80/carbopol systems. Microcalorimetry titration data made it possible to conclude that Tween 80/carbopol interaction, at 298K, is an enthalpy-driven process due to stabilization of Tween 80 units inside the polymer network. In contrast, Pluronic F-127/carbopol association (endothermic process) occurs owing to a gain in entropy when polymer-surfactant interaction allows the restoration of free water hydrogen-bonding structure, resembling the micellization process.

Acrylates↗

PubMed2003

Poly(acrylic acid) microgels (carbopol 934)/surfactant interactions in aqueous media. Part II: Ionic surfactants.

The interaction of sodium dodecylsulfate (SDS) or benzalkonium chloride (BkCl) with carbopol microgels (0.25% (w/w)) in water was studied through pH, trasmittance, viscosity, surface tension, conductivity, fluorescence, oil solubilization, and microcalorimetry measurements. In the case of the anionic surfactant, enthalpy-driven hydrophobic absorption of SDS into carbopol microgels began when SDS concentration reached 0.05-0.08% and ended around 0.6%. These concentrations were estimated as the critical aggregation (cac) and saturation binding concentration, respectively. The hydrophobic absorption of the surfactant accompanied by its counter-ion caused carbopol microgels to swell and promoted the occurrence of bridges among several carbopol microgels. As a consequence, the consistency of the dispersions increased significantly. Above binding saturation, further addition of SDS produced a shielding effect among the anionic charges of carbopol and its dehydration, which was shown as a decrease in the viscosity of the dispersions. At low shear rates, the dispersions behaved as pseudoplastic owing to orientation of carbopol/SDS aggregates in the flow direction. Increasing shear rates caused the inter-microgel bridges to break, the water layer surrounding them to diminish, and the system to show a shear-thickening behavior. In contrast, carbopol/BkCl aggregates showed shear-thickening flow in the whole range of shear rates analyzed. Electrostatic interactions between BkCl and carbopol carboxylic groups release protons to the medium and decrease the internal osmotic pressure of the microgels. This may favor the establishment of hydrophobic interactions among surfactant tails, and induces carbopol microgels to collapse. The cac was approximately 0.01% BkCl. Saturation binding occurred at 0.3-0.5%, indicating that only 25-40mol% carboxylic groups were neutralized with BkCl. The shrinking of carbopol microgels as BkCl is absorbed prevents additional surfactant molecules from interacting with the remaining carboxylic groups. Microcalorimetry assays revealed that the aggregation process occurred with a strong gain in enthalpy.

Acrylates↗

PubMed2003

Influence of cationic cellulose structure on its interactions with sodium dodecylsulfate: implications on the properties of the aqueous dispersions and hydrogels.

The interactions of sodium dodecylsulfate (SDS) with the aqueous dispersions and the chemically cross-linked hydrogels of two cationic hydroxyethylcelluloses, polyquaternium-4 (PQ-4) and polyquaternium-10 (PQ-10), commonly used in cosmetics and in topical drug delivery devices, were analyzed. This surfactant was chosen not only for its interest as excipient, but also as a model of the amphiphilic behavior shown by many drugs. In aqueous dispersions, the interaction process was studied through transmittance, surface tension, fluorescence, microcalorimetry titration, viscosity and oscillatory rheometry measurements. The ammonium/sulfate groups ratios at the critical aggregation concentration (0.05% SDS) were 2.61 for PQ-4 and 4.02 for PQ-10; while at the saturation concentration (0.25% SDS), these ratios decreased to 0.52 and 0.80, respectively. The binding process, through ionic and hydrophobic interactions, was strongly exothermic in both water and aqueous NaCl 0.9% solution, which indicates that the salt did not modify the interaction. PQ-4/SDS dispersions had, for all SDS concentrations, higher viscous (G") and, especially, elastic (G') moduli than the polymer solution. The maxima in G' and G" (four orders of magnitude greater than PQ-4 only solutions) were observed at the SDS concentrations in which the ammonium/sulfate groups ratio is close to 1. PQ-10/SDS dispersions behaved very differently and, near the neutralization point, the precipitation of the system caused G" to decrease abruptly, and G' to disappear. The contrasting behavior of the two cationic celluloses may be attributed to their structural differences; PQ-4 has less ammonium groups, in small chains grafted to the cellulose backbone, and more free hydroxyethyl substituents than PQ-10. Therefore, although the neutralization of charges causes the formation of a neutral polyampholyte, the presence of the free hydrophilic hydroxyethyl groups in PQ-4 avoids the precipitation of the aggregates and contributes to the establishment of a three-dimensional network. In contrast, in PQ-10, the ammonium groups are directly bonded to the hydroxyethyl substituents and, in the aggregation process, they may be included in the polyampholyte complex, contributing to the precipitation. This different behavior was easily seen in the surfactant-induced shrinking of the hydrogels around the charges neutralization. Although the SDS binding isotherms were very similar, PQ-10 hydrogels decreased their volume up to 20 times at the neutralization point, while PQ-4 hydrogels reduced their initial volume only three times under the same conditions. These results suggest that the phase transitions of the hydrogels may be used as quick predictors of the behavior of the polymer dispersions.

Cations↗

PubMed2001

Incorporation of small quantities of surfactants as a way to improve the rheological and diffusional behavior of carbopol gels.

This paper analyzes the effects of Tween 80, Pluronic F-127, sodium dodecylsulfate (SDS), and benzalkonium chloride on the macro and microviscosity of Carbopol 934NF (0.25-0.50 g/dl) pharmaceutical gels. Carbopol/surfactant interactions, which were reflected in changes in the intrinsic viscosity of the polymer and in shifts of IR spectra bands of films, considerably modified the rheological properties of the gel (flow and oscillatory rheometry) and the diffusion coefficients of polystyrene particles (dynamic light scattering, DLS). At pH 4, any surfactant at a concentration of 0.01 g/dl promoted interpolymer connections producing an open three-dimensional network with maximum viscous and elastic moduli, which does not disturb the diffusive movement of polystyrene particles. An increase in non-ionic surfactant (0.05-0.50 g/dl) gradually decreased viscosity and elasticity since there were more surfactant molecules to surround each carbopol particle, forming intrapolymeric micelles and breaking the interpolymer connections. This macroscopic effect is, however, not reflected in a decrease but in an increase in microviscosity (estimated by DLS) owing to the formation of larger carbopol/surfactant aggregates and free micelles that contribute significantly to the obstruction of the diffusional path. Both ionic surfactants decreased macroviscosity owing to ionic aggregation (benzalkonium chloride) or increase in ionic strength (mainly SDS), while the repercussion on the diffusion of polystyrene particles was dramatically different, and was hindered (due to the carbopol/surfactant aggregates) or enhanced (due to the shrinking of carbopol microgels), respectively. At pH 7.4, the ionization of the carboxylic groups produced an expansion of the polymer chains accompanied by a huge increase in viscosity and elasticity and a decrease in diffusion coefficients in comparison with those obtained at pH 4. The effects of the surfactants were similar to those observed at pH 4 but less intense. Chloramphenicol release studies (Franz-Chien cells) revealed that 0.01 g/dl surfactant did not affect the diffusion while a change in pH dramatically altered the process. The results show that by choosing the appropriate proportion of the most suitable surfactant, it is possible to modulate the flow behavior, elastic properties, and diffusional microenvironment of carbopol gels, without losing the pH-dependent gelling ability, which could improve the suitability of carbopol gels for drug delivery through different routes.

Acrylic Resins↗

PubMed2001

Rheological evaluation of the interactions between cationic celluloses and Carbopol 974P in water.

This paper reports on the influence of the structural properties of two cationic hydroxyethylecelluloses, polyquaternium-4 (PQ-4; 1.13-1.27% N) and polyquaternium-10 (PQ-10; 1.88-1.95% N), on the rheological behavior of their dispersions and of the dispersions of their blends with Carbopol 974P (60.9% COOH) in water. Dynamic shear oscillation measurements showed that the rheological behavior of 1 and 2% (w/w) cellulose polymers was mainly viscous. Flow curves of PQ-10 dispersions presented a higher consistency and pseudoplasticity than PQ-4 dispersions, in which the thixotropy was higher. Structural features, such as type and distribution of substituents and molecular weight, explain why they behave different. The presence of 0.00125-0.02% Carbopol in diluted cationic cellulose (0.01-0.08%) dispersions produced an important decrease in viscosity, due to a strong associative process via an electrostatic interaction phenomenon. Similar results were obtained when sodium acetate was added instead of Carbopol. In contrast, in the concentrated range (1% cellulose polymer), the viscous (G") and especially the elastic (G') moduli of the dispersions increased monotonically with Carbopol concentration (0.010-0.125%) and became physical gels, except in the proximity of the neutralization of the ammonium groups (0.07% Carbopol for PQ-4, and 0.1% Carbopol for PQ-10) in which G" and G' decreased. The concentrated dispersions showed pH-sensitivity when the Carbopol added was around or above the neutralization point. In dispersions with this composition, consistency increased dramatically when pH changed from 4.5 to 7.4. This property can open a wide range of applications, especially in the pharmaceutical field to prepare gelling in situ systems.

Acrylates↗

PubMed2001

Extrusion-Spheronization of blends of carbopol 934 and microcrystalline cellulose.

We evaluated the effects of several process variables on the pharmaceutical and drug release properties of extrusion-spheronization pellets of blends of Carbopol 934 and microcrystalline cellulose (MCC) containing a high proportion of Carbopol. The model drug was theophylline. Rheological monitoring during mixing was by mixer torque rheometry. Carbopol:MCC blends wetted with a CaCl2 solution showed different rheological behavior compared to blends with a high proportion of MCC wetted with water only. In contrast to previous suggestions, the optimal wetting point for extrusion did not coincide with the point of peak torque, but occurred just beyond this point, at much lower torque. The influence of process variables on blend properties was investigated with a three-variable factorial design (Carbopol:MCC ratio, wetting liquid proportion, CaCl2:Carbopol ratio), and the influence of process variables on pellet properties with a four-variable design (the variables listed plus extrusion screen hole diameter). Blend torque values were strongly influenced by CaCl2 proportion, while mean pellet diameter was influenced by Carbopol:MCC ratio. Mean pellet diameter also differed depending on whether the pellets contained theophylline. The observed among-formulation differences in theophylline release kinetics were largely explained by differences in pellet size and theophylline hydration state. Compaction of pellets to form tablets markedly modified the drug release profile, making it biphasic.

Acrylates↗

PubMed2000

Interactions between liposomes and hydroxypropylmethylcellulose.

The characteristics of the adsorption process of hydroxypropylmethylcellulose (HPMC) of molecular weight 35400 Da and nominal viscosity 100 cps onto liposomes prepared with different egg lecithin-cholesterol molar ratios were examined. Adsorption isotherms were constructed and analysed to investigate the mechanisms implicated in the incorporation of the polymer to the interface. Only the isotherms obtained with cholesterol-free liposomes were fitted with Langmuir model. When cholesterol is present in the composition they present a sigmoidal slope. The mechanism of adsorption depends on liposome composition being the main force that drives polymer adsorption of hydrophobic nature. The apparent volumes of HPMC indicate that the conformation of the adsorbed macromolecules depends on liposome composition. Hydration enthalpy values show that adsorbed polymers do not give more hydrophilic systems after freeze-drying as expected with the hydrophilic characteristics of the HPMC.

Adsorption↗

PubMed2000

Evaluation of low-substituted hydroxypropylcelluloses (L-HPCs) as filler-binders for direct compression.

The aims of this study were to assess the potential value of low-substituted hydroxypropylcelluloses (L-HPCs) as excipients of direct compression, and to investigate relationships between the chemical and physical properties of the polymers and (a) the powder rheological behavior and (b) drug release profiles from direct compressed tablets elaborated with (1:1) theophylline:L-HPC mixtures. Experiments were performed with five L-HPC varieties of different nominal particle sizes and degree of substitution. The products were characterized with regard to the moisture content, density, IR and Raman spectroscopy, hydroxypropyloxy content, heat of hydration, particle size, specific surface and porosity, and important differences were found in relation with all these properties. The differences in specific surface principally determine the flow and compaction properties of the powders, and the mechanical and microstructural properties of the tablets. The control of the hydroxypropyloxy content and the particle size of the L-HPCs allow the theophylline release profile to be regulated.

Cellulose↗

PubMed2000

Interactions between hydroxypropylcelluloses and vapour/liquid water.

Understanding of the uptake of water vapour or liquid water by cellulose-based polymers is important because of the influence of these processes on many of the biologically or technologically relevant properties of these polymers. In this work we studied these processes in the cases of twelve hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively), characterization of which showed significant differences in structural and physical parameters (substitution pattern, crystallinity, particle size, specific surface area, and intraparticular porosity). Water vapour sorption-desorption isotherms determined to characterize the uptake of water vapour were fitted well by the Young-Nelson model, the optimized parameters of which indicated that at all relative humidities the capacity to bind water vapour as a surface monolayer is greater for HPCs than L-HPCs, but the capacity to absorb water vapour internally is greater for L-HPCs than HPCs. Guggenheim-Anderson-deBoer (GAB) models fitted the sorption-desorption isotherms less well. Differential scanning calorimetry (DSC) experiments showed all sorbed water vapour to be held as non-freezing water. Isoperibol microcalorimetry experiments carried out to investigate interactions with liquid water showed enthalpies of hydration/dissolution of between -62.86 and -71.35 J g(-1) for L-HPCs and between -82.95 and -99.80 J g(-1) for HPCs, and DSC showed average numbers of non-freezing water molecules per polymer repeat unit of 2.65-4.19 for L-HPCs and 18.10-22.42 for HPCs. DSC characterization of the kinetics of the water uptake by 10 mg compacts obtained by direct compression of hydroxypropylcelluloses showed faster uptake by L-HPC compacts than by HPC compacts, among which there were significant differences in capacity for diffusive uptake. The explanations of the above differences in terms of the different substituent contents, particle sizes and porosities of the HPCs is supported by multiple linear regression analyses.

Cellulose↗

PubMed2000

The stability of theophylline tablets with a hydroxypropylcellulose matrix.

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20 degrees C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).

Cellulose↗

PubMed1999

Microviscosity of hydroxypropylcellulose gels as a basis for prediction of drug diffusion rates.

This study investigated the influence of the rheological properties of hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties (mean molecular weight between 5x105 and 1.2x106, nominal viscosity between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion coefficients at 37 degrees C ranged from 3.5x10-7 to 1.1x10-3 cm2/min, and were in all cases markedly higher than those predicted on the basis of gel macroviscosity as determined by capillary viscometry. In general, the theophylline diffusion coefficient declined exponentially with HPC concentration; in the case of the lowest-molecular-weight HPC, however, the diffusion coefficient remained constant to HPC concentrations of up to 0.8%, probably because of the high entanglement concentration of the HPC. Gel microviscosities as determined by dynamic light scattering (DLS) with latex microspheres (162 nm diameter) were considerably lower than the macroviscosities determined by capillary viscometry, and similar to microviscosities estimated on the basis of theophylline diffusion. Nevertheless, macroviscosity was correlated with microviscosity, suggesting that it is of value for approximate estimates of rates of diffusion of theophylline from HPC gels.

Cellulose↗

PubMed1999

Degradation of hydroxypropylcellulose by Rhizomucor: effects on release from theophylline-hydroxypropylcellulose tablets.

The stability of several varieties of hydroxypropylcellulose was monitored during 3 years of storage (1) under the conditions recommended by manufacturers and official pharmacopoeias (simple storage in closed containers) and (2) at zero relative humidity. After 1 year, severe degradation of the varieties with lower initial pH and particle size stored at ambient relative humidity was shown by changes in their molecular weight and in the pH and apparent viscosity of 2% aqueous dispersions. Microbiological analyses showed the observed degradation to be attributable to the action of fungi of the genus Rhizomucor. The changes in apparent viscosity significantly affected the release of theophylline from direct compression tablets formulated with the degraded excipients.

Cellulose↗

PubMed1999

A comparison of gas-liquid chromatography, NMR spectroscopy and Raman spectroscopy for determination of the substituent content of general non-ionic cellulose ethers.

This paper describes and compares three techniques that can be used to characterize the substituent content of hydroxypropylcellulose (HPC and L-HPC) and hydroxypropyl methylcellulose (HPMC): gas-liquid chromatography (GLC) with a BP1 column and FI detection, 13C-NMR spectroscopy of hydrolysed samples, and Raman spectroscopy. GLC and 13C-NMR spectroscopy both allow independent quantification of hydroxypropoxyl and methoxyl contents. 13C-NMR spectroscopy, though requiring lengthier sample preparation, has the advantage of also quantifying the degree of substitution at each substitutable glucopyranose hydroxyl. Raman spectroscopy may be useful for rapid approximate estimation of hydroxypropoxyl content.

Calibration↗