M. Bertoni

Influence of mucin type on polymer-mucin rheological interactions

There are numerous in vitro methods with which to investigate the mucoadhesive properties of polymers. One recent method is based on the measurement of rheological interactions between polymer and mucin, which implies the use of mucins isolated from the mucous tissue. The extraction and purification of glycoprotein fraction, which is responsible for rheological interaction, can modify the native structure of mucin or spoil it with exogenous substances. Therefore the particulars of the mucin employed (origin, purification grade, the effect of further treatments such as freezing or freeze-drying) are likely to be critical for the interaction. The aim of this work was to compare some commercial mucins of differing origin and grade of purification for their rheological interaction with well-known mucoadhesive polymers (polyacrylic acid and sodium carboxymethylcellulose). For polyacrylic acid, which is sensitive to ions, we found rheological interaction to be strongly influenced by mucin type. The removal of ions, with dialysis, improved the interaction. For sodium carboxymethylcellulose, which is less sensitive to ions, rheological interaction proved to be less dependent on mucin type and improved upon glycoprotein solubilization.

On the employment of lambda carrageenan in a matrix system. III. Optimization of a lambda carrageenan-HPMC hydrophilic matrix

The lambda carrageenan/HPMC ratio in matrix tablets has been optimized in order to obtain pH-independent release profiles of chlorpheniramine maleate, a freely soluble drug. Release profiles in acidic (pH1.2) and neutral (pH 6.8) media were fitted according to the Weibull and the power law models. Model independent parameters(t50% and the percentage of drug released after 2 h) were also calculated. The Weibull parameters were found suitable to describe the dependence of the release profiles on matrix composition. Preparation and testing of the optimized formulation showed linear and pH-independent release profiles lasting about 24 h, in good accordance with the values predicted by the optimization procedure.

Investigation on bonding and disintegration properties of pharmaceutical materials

Abstract The disintegration properties of differing pharmaceutical materials having well-known bonding mechanisms were investigated in various media. The materials were sodium chloride, lactose monohydrate and microcrystalline cellulose. They bind mainly with intermolecular bonds and are therefore supposed to loose bonding strength in media with a suitable dielectric constant. The media used were water, methanol and isopropanol. The tablets were prepared under controlled conditions and checked for disintegration time, liquid penetration and disintegration force development. Whenever disintegration did not occur, the crushing strength after soaking in the various media was measured. For microcrystalline cellulose, the swelling properties of the powder material were also measured. The results obtained show that the annihilation/weakening of intermolecular bonds, which are due to the environmental changes in dielectric constant, may play a role in the disintegration of tablets. However, it has to be taken in consideration that the medium must be capable of penetrating into the tablet, that the extent of bond weakening depends on the dielectric constant of the media and that the mechanical stress is likely to be decisive in provoking tablet disintegration. The type of disintegration that is caused by the annihilation/weakening of intermolecular bonds is not accompanied by any force development, therefore it may be referred to as a passive mechanism of disintegration. Whenever disintegration is accompanied by force development, this may be referred to as an active mechanism of disintegration. Swelling is always present in this mechanism .

Characterization of mucin interaction with three viscosity grades of sodium carboxymethylcellulose. Comparison between rheological and tensile testing

Abstract In a previous work, attempts were made to correlate the rheological interaction between polymer and mucin with the detachment force, measured (with tensile testing) for the same polymer-mucin combination. The polymers examined included natural gums, semisynthetic derivatives and synthetic products. The lack of correlation between rheological and tensile parameters was attributed to the diversity of chemical nature of the polymers considered. In the present work the correlation between rheological and tensile parameters of three viscosity grades of the same polymer (sodium carboxymethylcellulose) was studied. Isoviscous solutions of the three viscosity grades were analyzed for rheological interaction with mucin (with a CS rheometer) and for detachment force (with tensile testing). The relationship found between the rheological and tensile parameters proved that the strengthening of the polymer-mucin interface is linked to the rheological changes that occur when the polymer is mixed with mucin.

Influence of medium on dissolution-erosion behaviour of Na carboxymethylcellulose and on viscoelastic properties of gels

Abstract The relevance of the rheological properties of a gelled polymer on its dissolution behaviour was investigated in the case of a high viscosity grade Na carboxymethylcellulose (NaCMC). Creep viscosity and oscillatory test parameters were measured on NaCMC gels in distilled water and in pH 6.8 phosphate buffer. Gel concentration ranged between 2.5 and 4.0% w/w. Polymer erosion from gels and from tablets was also tested in the same media and the results were in line with rheological data. Moreover, the effect of ionic strength and ion type on both rheological properties of gels and erosion from tablets was assessed. A relationship was also found in this case between rheological parameters and erosion rates. The importance of ionic strength on the rheological and erosion behaviour of polyelectrolytes such as NaCMC is highlighted.

Physico-chemical characterization and tabletting properties of Scleroglucan

Abstract The aim of this work was to describe those characteristics of scleroglucan that are relebant to its employment as a sustained release agent in hydrophilic swellable matrices. Besides a brief review of the rheological properties of scleroglucan, various measurements have been effected to define the physical and mechanical properties of scleroglucan and to forecast its behavior as a matrix carrier.

Comparative Rheomechanical and Adhesive Properties of Two Hydrocolloid Dressings: Dependence on the Degree of Hydration

AbstractHydration is believed to modify the mechanical properties (resistance to stress) and the rheological (viscoelastic) properties of hydrocolloid dressings. Rheomechanical properties in turn influence adhesional properties. In this work the relationships between the degree of hydration and the rheomechanical and the adhesive properties of two different commercial dressings (regular and nondispersive) were investigated. The two dressings showed different hydration characteristics. The regular dressing takes up water rapidly and tends to reach saturation after 12 hr. As the dressing swells and loses its integrity there is an accompanying reduction of both rheomechanical and adhesive properties. The nondispersive dressing exhibits a linear water uptake profile over extended periods of hydration up to 4 days. It does not swell and its rheomechanical and adhesive properties remain unchanged after hydration, The comparative evaluation of the results obtained with the various methods points to the relevance...

Description and validation of an apparatus for gel strength measurements

Abstract The increasing interest in gel-like dosage forms and in systems that undergo gelification upon contact with biological fluids (like hydrogels and hydrophilic swellable matrices) suggests the importance of gel strength measurements. For example, it has been suggested that the strength rather than the viscosity of the gel layer plays a major role in drug release from hydrophilic matrices. Nevertheless, probably due to the lack of a user-friendly and suitable apparatus, the gel strength parameter is not routinely investigated in preformulation and formulation studies of such dosage forms. In the present work, an apparatus, which had been previously designed for the characterisation of industrial polymers, was modified to make it suitable for measuring the gel strength of pharmaceutical systems and its performance was validated under differing experimental conditions. The results of gel strength measurements effected on hydroxypropylmethylcellulose solutions and on κ-carrageenan and carboxyvinyl polymer gels are reported herein.

Dissolution Enhancement of an Insoluble Drug by Physical Mixture with a Superdisintegrant: Optimization with a Simplex Lattice Design

The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.

Comparative evaluation of hydrocolloid dressings by means of water uptake and swelling force measurements: II

Abstract Hydrocolloid dressings are composite systems made of a hydrophobic matrix and a hydrophilic phase, which renders them capable of absorbing water. In a previous paper, water uptake and swelling force measurements, carried out in separate experiments were used to characterise and compare different hydrocolloid dressings. In particular, swelling force measurements provide information on the modifications induced by water absorption, which influence the in vivo performance of patches. In the present work, simultaneous measurements of water uptake and swelling force were carried out on some hydrocolloid dressings in order to achieve a better understanding of the relationship between the two phenomena. A computer-aided apparatus, which is a combination of the two apparatus formerly described for separate water uptake and swelling force measurements, was set up. A parameter referred to as the ‘force equivalent’, which represents the capability of the patch of transforming water uptake into swelling force, was used for characterising the various patches. This parameter is suitable to differentiate between patches characterised by similar composition but different hydration and swelling propensity. The patches examined in the present work could be divided into two groups, depending on their greater or lesser capability of transforming water uptake into swelling force. The time course of the derivative of the swelling force vs water uptake curve allowed a further differentiation between and within groups. It is envisaged that both the force equivalent value and the rate of attainment of force equivalent are related to adhesion performance.