Italo Colombo

Drug release from an ensemble of swellable crosslinked polymer particles

This paper presents a new model suitable to describe the drug release from drug delivery systems constituted by an ensemble of drug loaded crosslinked polymer particles. The model accounts for the main factors affecting the drug release such as the particle size distribution, the physical state and the concentration profile of the drug inside the polymeric particles, the viscoelastic properties of the polymer-penetrant system and the dissolution-diffusion properties of the loaded drug. In order to check the validity of the model, release experiments were performed by using crosslinked polyvinyl-pyrrolidone (PVP) particles and two different model drugs, MAP (medroxyprogesterone acetate) and TEM (Temazepam). MAP and TEM were chosen because of their completely different dissolution behaviours in water. In particular, TEM undergoes a phase transition to the crystalline state upon dissolution when it is loaded in the polymeric network in the amorphous state. The comparison with the experimental results confirms that the most important factors determining the drug release kinetics can be properly accounted for.

Experimental determination of the theophylline diffusion coefficient in swollen sodium-alginate membranes

In this paper attention is focused on the determination of the drug diffusion coefficient in a swollen polymeric membrane referring to a recent mathematical model (linear model). The main advantage deriving from its use is that, despite its analytical nature and its ability to account for the most important aspects characterising a permeation experiment, it can also be applied in the case of thick membranes. To check the model reliability, a comparison is made with a more complex numerical model and with a largely employed model in terms of data fitting quality. To this purpose, particular care is devoted to the experimental and theoretical tools employed to calculate the auxiliary parameters required by the three models, and with the aim of getting a drug diffusion coefficient value as accurate as possible. Theophylline was chosen as model drug owing to its wide employment in the pharmaceutical field. Membranes were prepared with sodium alginates hydrogels at three different polymer concentrations. The present analysis demonstrates the reliability of the linear model and reveals that the theophylline diffusion coefficient is not significantly affected by the polymer concentration. Indeed, such a parameter is reflected in different membrane thicknesses rather than in different mesh sizes of the polymeric network.

Investigation of surface properties of some polymers by a thermodynamic and mechanical approach: possibility of predicting mucoadhesion and biocompatibility

Mucoadhesive properties of several polymers, such as sodium alginate, hydroxypropylmethyl cellulose, scleroglucan, xanthan gum, polyacrylic acid (Carbopol), and poly co-(methyl vinyl ether-maleic anhydride) (Gantrez), have been investigated by comparing a thermodynamical and a mechanical approach. Surface properties of polymers in the dry state have been studied by contact angle measurements and thermodynamical parameters derived by using different equations. This tensile adhesive strength of polymers in hydration conditions was measured by a modified DuNoy tensiometer. Comparison of the two different approaches has allowed us to conclude that thermodynamical consideration on surface energy can be used to evaluate mucoadhesive properties of materials. Data obtained with the two methods yielded a good linear correlation. Calculation of surface free energy of the considered materials also allowed a prediction of the water-polymer interface free energy: biocompatibility, defined according to the minimal interfacial free energy concept, could consequently be evaluated.

Mathematical modelling of drug permeation through a swollen membrane.

This work proposes two different mathematical models (linear and numerical) able to simulate the drug permeation through a swollen membrane sandwiched by two external layers (trilaminate system). Moreover, a solid drug dissolution phenomenon in the donor compartment may be accounted for. Indeed, this is a situation that may often occur in permeation experiments. An insufficient stirring of the donor and of the receiver volume may give rise to two sandwiching layers and the target of a constant drug concentration in the donor compartment may be accomplished by putting a solid drug amount in the saturated donor solution. The linear model shows the advantage of having an analytical expression which extremely simplifies the calculation of the drug diffusion coefficient D inside the membrane. Its main drawback lies in the fact that it works only for thin trilaminate systems. The numerical model is more general than the linear one, as it works for all kind of trilaminate thickness and it may account for a solid powder dissolution in the donor compartment. Of course, it does not have an analytical solution and, thus, the D determination is less easy to perform as the numerical model is more time consuming than the linear one. These two models are then compared with the classical approach developed by Flynn and Barrie in order to better define its validity limits.

Molecular recognition by contact angle: proof of concept with DNA hybridization.

A molecular recognition reaction supported by a solid-phase assay drives a specific change in the solid-solution interfacial tension. This prompts contact angle (CA) analysis, being a straightforward route to evaluate this property, to play the unedited role of label-free probe of the reaction. The concept is proven by the successful recognition of DNA hybridization and is further supported by the agreement between the results and the underpinning thermodynamics.

Modeling phase transitions and sorption desorption kinetics in thermo-sensitive gels for controlled drug delivery systems☆

Abstract Phase equilibrium and kinetic models for describing the swelling of hydrogels are considered. The swelling equilibrium model is based on an effective Flory-Huggins model coupled with a phantom network model in the framework of the Flory-Rehner theory. The kinetic model used is that proposed by Camera-Roda and Sarti, which is capable to describe non Fickian diffusion that occures in hydrogels. The models are coupled and applied to non charged thermo-sensitive hydrogels and the results obtained show a good agreeement between experimental and calculated data.

Reduction of melting temperature and enthalpy of drug crystals: Theoretical aspects

This review deals with the mathematical models describing the reduction of melting temperature and enthalpy of solids in the nano-size range. In particular, the attention focuses on the thermodynamic based models that are theoretically solid and can be suitably used in the case of organic drugs. Indeed, while much effort has been put in the past to study the melting of metal nano-crystals, little work has been done for organic drug nano-crystals. However, due to the high potential of drug nano-crystals (their solubility increases with size reduction), this theme has become more and more important in the pharmaceutical field. Accordingly, this review, after illustrating the physical frame of drug melting, focuses on the thermodynamic aspects required to describe the melting of spherical and not spherical nano-crystals. Finally, the reliability of some models is tested against the results coming from X-rays analysis in the case of two organic drugs (griseofulvin and nifedipine). This test proved models strength.

Determination of the drug diffusion coefficient in swollen hydrogel polymeric matrices by means of the inverse sectioning method

Abstract The accurate knowledge of the diffusion coefficient D g of an active drug within a swollen polymeric hydrogel matrix plays a determinant role in the analysis of the controlled release processes, in the prevision of their kinetics and in the design and formulation of efficient controlled release drug delivery systems. In this paper, we applied the so-called inverse sectioning method to a scleroglucan hydrogel matrix loaded with theophylline, and illustrated a procedure for a reliable estimation of D g . This crucial parameter is calculated by correlating the experimental data with the model resulting from the analytical solution of the second Fick law in one dimension, obtained under the appropriate initial and boundary conditions. The quality of the adopted model and the uncertainty on the calculated value of D g are discussed on a statistic basis.

APPARENT NON-FICKIAN RELEASE FROM A SCLEROGLUCAN GEL MATRIX

Abstract Hydrogels, and particularly biopolymeric hydrogels, have recently received tremendous interest as controlled release systems for their peculiar features such as high biocompatibility, biodegradability, bioadhesivity, chemical and thermal resistance and good mechanical properties. Among biopolymers, the exocellular microbial polysaccharide scleroglucan appears to be particularly well suited for the formulation of monolithic hydrogel matrices for controlled drug release. In this work we studied the macroscopic factors influencing the kinetics of a model drug release (theophylline) from a scleroglucan hydrogel matrix (2%w/w) and modeled the relevant experimental results. The evidences for the release experiments indicate that the kinetics of the processes follow an apparently non-Fickian behavior under different active drug concentration, temperature and stirring speed. However, by considering the peculiar nature of the hydrogel matrix and the geometrical features of the experimental setup in the fo...

On the thermodynamics of biomolecule surface transformations.

Biological surface science is receiving great and renewed attention owing the rising interest in applications of nanoscience and nanotechnology to biological systems, with horizons that range from nanomedicine and biomimetic photosynthesis to the unexpected effects of nanomaterials on health and environment. Biomolecule surface transformations are among the fundamental aspects of the field that remain elusive so far and urgently need to be understood to further the field. Our recent findings indicate that surface thermodynamics can give a substantial contribution toward this challenging goal. In the first part of the article, we show that biomolecule surface transformations can be framed by a general and simple thermodynamic model. Then, we explore its effectiveness by addressing some typical cases, including ligand-receptor surface binding, protein thin film machines, nanomechanical aspects of the biomolecule-nanoparticle interface and nanomechanical biosensors.