Dissolution of irregularly-shaped drug particles: mathematical modelling.

The prediction of drug dissolution profiles is crucial for elucidating the pharmacokinetic behaviour of drugs and the bioavailability of dosage forms. In this work, we develop a mathematical model to describe the dissolution process of irregularly shaped particles. We use a complete dissolution model that accounts for both surface kinetics and convective diffusion. The mechanistic relationship between the mass transfer coefficient and the local curvature is derived from the fundamental physical laws governing these processes. Our model theoretically shows that the dissolution rate depends nonlinearly on the surface curvature. The subsequent recrystallization process in the bulk fluid is also considered. The main result of this work is its simplicity, since only two coupled nonlinear ordinary differential equations are needed to describe the dissolution process. Another remarkable advantage is the possibility to determine the model parameters using common independent techniques, so that the importance of the wettability of solids on the dissolution process can be evaluated. Finally, the proposed model demonstrated the importance of particle shape in describing the experimental dissolution data of theophylline monohydrate.

Investigation on the thermal gelation of Chitosan/ß-Glycerophosphate solutions.

This work deals with the effect of temperature on the thermal-gelation process of water solutions containing chitosan ß-glycerolphosphate disodium salt hydrate. In particular, the attention is focused on the role played by temperature on the gel final properties, a very important aspect in the frame of drug delivery systems. The study was performed by combining rheology and low field nuclear magnetic resonance, two approaches that revealed to be highly synergic as they can detect different aspects of the developing polymeric network. This study indicates that 30 °C represent a sort of threshold for both the gelation kinetics and the gel final properties. Indeed, above this temperature, gelation kinetics was rapid and yielded to a strong gel. On the contrary, a slow kinetics and a final weak gel occurred below 30 °C. Finally, rheology and low field NMR allowed, independently, evaluating the time evolution of the network mesh size upon gelation.

Role of sonication pre-treatment and cation valence in the sol-gel transition of nano-cellulose suspensions.

Sol-gel transition of carboxylated cellulose nanocrystals has been investigated using rheology, SAXS, NMR and optical spectroscopies to unveil the distinctive roles of ultrasound treatments and addition of various cations. Besides cellulose fiber fragmentation, sonication treatment induces fast gelling of the solution. The gelation is independent of the addition of cations, while the final rheological properties are highly influenced by the type, concentration and sequence of the operations since the cations must be added prior to sonication to produce stiff gels. The gel elastic modulus was found to increase proportionally to the ionic charge rather than the cationic size. In cases where ions were added after sonication, SAXS analysis of the Na+ hydrogel and Ca2+ hydrogel indicated the presence of structurally ordered domains in which water is confined, and 1H-NMR investigation showed the dynamics of water exchange within the hydrogels. Conversely, separated phases containing essentially free water were characteristic of the hydrogels obtained by sonication after Ca2+ addition, confirming that this ion induces irreversible fiber aggregation. The rheological properties of the hydrogels depend on the duration of the ultrasound treatments, enabling the design of programmed materials with tailored energy dissipation response.

Rheology of Laponite-scleroglucan hydrogels.

Both Laponite and scleroglucan can find several applications in various fields (from industrial to biomedical one) in virtue of their peculiar features and rheological properties displayed in aqueous phases. Structural states of Laponite dispersions strongly depend on concentration and ionic strength. When attractive and repulsive interparticle interactions are so effective that they lead to arrested states (attractive gel or repulsive glass), the rheological behavior of the dispersion undergoes a sharp transition, from quasi-Newtonian to markedly shear thinning and viscoelastic. Conversely, scleroglucan solutions gradually change to weak gels with increasing polymer concentration. The present work is concerned with aqueous Laponite-scleroglucan mixed systems, obtained according to different preparation modes, and is aimed at examining how much the content and proportion of both components affect the viscoelastic and flow properties of the mixed system.

Topological characterization of a bacterial cellulose-acrylic acid polymeric matrix.

This paper focuses on the micro- and nano-topological organization of a hydrogel, constituted by a mixture of bacterial cellulose and acrylic acid, and intended for biomedical applications. The presence of acrylic acid promotes the formation of two interpenetrated continuous phases: the primary "pores phase" (PP) containing only water and the secondary "polymeric network phase" (PNP) constituted by the polymeric network swollen by the water. Low field Nuclear Magnetic Resonance (LF NMR), rheology, Scanning Electron Microscopy (SEM) and release tests were used to determine the characteristics of the two phases. In particular, we found that this system is a strong hydrogel constituted by 81% (v/v) of PP phase the remaining part being occupied by the PNP phase. Pores diameters span in the range 10-100 µm, the majority of them (85%) falling in the range 30-90 µm. The high PP phase tortuosity indicates that big pores are not directly connected to each other, but their connection is realized by a series of interconnected small pores that rend the drug path tortuous. The PNP is characterized by a polymer volume fraction around 0.73 while mesh size is around 3 nm. The theoretical interpretation of the experimental data coming from the techniques panel adopted, yielded to the micro- and nano-organization of our hydrogel.

Therapeutic potential of nucleic acid-based drugs in coronary hyper- proliferative vascular diseases.

The thickening of the vessel wall (intimal hyperplasia) is a pathological process which often follows revascularization approaches such as transluminal angioplasty and artery bypass graft, procedures used to re-vascularize stenotic artery. Despite the significant improvements in the treatment of intimal hyperplasia obtained in the last years, the problem has not completely solved. Nucleic acid based-drugs (NABDs) represent an emergent class of molecules with potential therapeutic value for the treatment of intimal hyperplasia. NABDs of interest in the field of intimal hyperplasia are: ribozymes, DNAzymes, antisense oligonucleotides, decoy oligonucleotides, small interfering RNAs and micro interfering RNAs. These molecules can recognize, in a sequencespecific fashion, a target which, depending on the different NABDs, can be represented by a nucleic acid or a protein. Upon binding, NABDs can down-modulate the functions of the target (mRNA/proteins) and thus they are used to impair the functions of disease-causing biological molecules.In spite of the great therapeutic potential demonstrated by NABDs in many experimental model of intima hyperplasia, their practical use is hindered by the necessity to identify optimal delivery systems to the vasculature. In the first part of this review a brief description of the clinical problem related to intima hyperplasia formation after revascularization procedures is reported. In the second part, the attention is focused on the experimental evidences of NABD therapeutic potential in the prevention of intimal hyperplasia. Finally, in the third part, we will describe the strategies developed to optimize NABD delivery to the diseased vessel.