J.L. Gómez-Amoza

Effect of country of origin on the properties of microcrystalline cellulose

Abstract The characteristics of four brands of microcrystalline cellulose manufactured in Finland, India, Ireland and Japan have been determined; all four were nominally similar to Avicel PH 101. There were significant differences in lignin content, hemicellulose sugars content and composition, presence or absence of cellulose II, enthalpy of immersion, particle size and flow properties. Crystallinity correlated with water-cellulose interaction, and particle size with flow properties.

Effect of batch variation and source of pulp on the properties of microcrystalline cellulose

Abstract We have investigated the characteristics of three batches of microcrystalline cellulose supplied by the same manufacturer but differing in the manufacturing process employed and/or the type of wood pulp used as raw material. Significant differences were found as regards lignin and hemicellulose contents, percentage crystallinity (calculated from IR spectra and X-ray diffraction data), enthalpies of immersion and capacity for moisture absorption. There were close correlations between crystallinity and the parameters reflecting interaction between microcrystalline cellulose and water. All three varieties had very similar particle size distributions, but the variety obtained from non standard pulp had a significantly greater specific surface due to greater intraparticle porosity. These differences did not significantly affect parameters such as compressibility and mean yield pressure, but are nevertheless potential causes of differences in behaviour in pharmaceutical products.

Interfacial Adsorption of Polymers and Surfactants: Implications for the Properties of Disperse Systems of Pharmaceutical Interest

This review considers basic aspects of the interfacial adsorption of polymers and surfactants, with particular reference to the relevance of these processes for the formulation of pharmaceutical disperse systems. First, we discuss different approaches to the interpretation of adsorption isotherms, paying particular attention to systems containing more than one adsorbate. Second, we consider the implications of adsorption for the properties of suspensions, emulsions, and colloidal systems, particularly as regards the use of polymers and surfactants for stabilizing disperse systems, for controlling flocculation, and for modifying the biopharmaceutical behavior of colloidal drug carriers. Finally, we present a number of representative examples of the importance of adsorption of macromolecules in pharmaceutical systems.

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.

Usefulness of certain varieties of Carbomer in the formulation of hydrophilic furosemide matrices

Abstract This paper deals with the evaluation of the possible use of three types of Carbomer, with different molecular weights, in the formulation of hydrophilic furosemide matrices. To this purpose the effects of the most outstanding elaboration variables; type and proportion of polymer and maximum compression force on the mechanical and release characteristics of tablets are studied. The factorial designs that were used as the basis for the development of this study have made it possible, through the respective ANOVA, to identify the factors having a significant effect on the properties of the tablets. Among the effects observed, which were quantified by sequential multiple linear regression, with acceptable adjustment levels, one of the most noteworthy is the effect that the maximum compression force has on the dissolution efficiency of furosemide from the formulations, regardless that variety of Carbomer employed. In all cases, the furosemide dissolution profiles, whose dependency on the microporous structure has been discussed, were fit to a zero order releasing kinetics, pointing to an erosion mechanism.

Atenolol release from hydrophilic matrix tablets with hydroxypropylmethylcellulose (HPMC) mixtures as gelling agent: effects of the viscosity of the HPMC mixture

Abstract The aims of this study were to assess the potential value of hydroxypropylmethylcellulose (HPMC) mixtures as gelling agents in matrix tablets for hydrosoluble drugs, and to investigate relationships between gelling agent viscosity and the kinetics of drug release from such tablets. Experiments were carried out with MethocelR K100LV (an HPMC with nominal viscosity of 100 cP) and MethocelR K100M (an HPMC with nominal viscosity of 100000 cP). Rheological characterization of 2% dispersions of the polymers, and of 30:70, 50:50 and 70:30 mixtures, indicated that it is possible to obtain a wide range of rheological behaviours by mixing K100LV and K100M, and that the two polymers display rheological antagonism. Trials were carried out with atenolol tablets made with 40% or 80% gelling agent (i.e. K100LV, K100M or one of the K100LV:K100M mixtures). Analysis of drug dissolution profiles in 0.1 N HCI, on the basis of Higuchis model and the equation of Korsmeyer and coworkers, indicated that drug release was in all cases diffusion-limited. A negative relationship was observed between the Higuchi constant for each tablet type and the apparent viscosity of the corresponding gelling agent in aqucous dispersion. In addition, apparent viscosity was negatively related to rate of attrition, suggesting that the observed relationship between the Higuchi constant and apparent viscosity is a reflection of differences in attrition resistance.

Dicalcium phosphate dihydrate and anhydrous dicalcium phosphate for direct compression: A comparative study

Abstract Dicalcium phosphate dihydrate (Emcompress) and anhydrous dicalcium phosphate (Anhydrous Emcompress) for direct compression were compared as regards particle size distribution and flow properties, which were found to be similar for the two products, and microporous structure and compression properties, which differed markedly. Specifically, intraparticular porosity and mean yield pressure of the anhydrous product were greater than for the dihydrate. Several properties of compacts of both products were also compared: compacts of the anhydrous phosphate disintegrated much more rapidly in distilled water than those of the dihydrate, which was attributed to the greater porosity of the former compacts.

Influence of microcrystalline cellulose source and batch variation on the tabletting behaviour and stability of prednisone formulations

Abstract The characteristics of prednisone tablets formed by direct compression with six previously characterized microcrystalline celluloses (MCCs) were studied. MCCs of similar particle size produced tablets with similar mechanical and microstructural properties, but prednisone dissolution rate varied significantly with MCC particle size and chemical composition. When stored under conditions of high relative humidity, all formulations underwent significant changes in mechanical and drug release properties, which is attributed to interaction between MCC and water.

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.

Chemical structure and glass transition temperature of non-ionic cellulose ethers

Glass transitions of several non-ionic cellulose ethers differing in molecular mass and nature and amount of substituents were analyzed (as compressed probes) by differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (TMDSC@®), and oscillatory rheometry. In general, the low energy transitions accompanying the Tg of methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), and hydroxypropylcelluloses of low (L-HPC) or medium-high (HPC) degree of substitution were difficult to characterize using DSC. Non-reversing heat flow signals obtained in TMDSC experiments were more sensitive. However, the best resolution was obtained using oscillatory rheometry since these cellulose ethers undergo considerable changes in their storage and loss moduli when reaching the Tg. Oscillatory rheometry also appears as a useful technique to characterize the viscoelastic behavior and thermal stability of pharmaceutical tablets. Tg values followed the order HPC (105°C)<HPMC (170-198°C)<MC (184-197°C)<L-HPC (220°C). For HPMCs, the Tg increases as the methoxyl/hydroxypropoxyl content ratio decreases. The results indicate that Tg depends strongly on the structure of the cellulose ethers. In general, increasing the degree of substitution of cellulosic hydroxyls, the hydrogen bonding network of cellulose decreases (especially when the substituents cannot form hydrogen bonds) and, in consequence, Tg also decreases.