Spray congealing: An emerging technology to prepare solid dispersions with enhanced oral bioavailability of poorly water soluble drugs

The low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions

Analyticity and Integrabiity in the Chiral Potts Model

We study the perturbation theory for the general non-integrable chiral Potts model depending on two chiral angles and a strength parameter and show how the analyticity of the ground state energy and correlation functions dramatically increases when the angles and the strength parameter satisfy the integrability condition. We further specialize to the superintegrable case and verify that a sum rule is obeyed.Comment: 31 pages in harvmac including 9 tables, several misprints eliminate

Completeness of the Bethe Ansatz solution of the open XXZ chain with nondiagonal boundary terms

A Bethe Ansatz solution of the open spin-1/2 XXZ quantum spin chain with nondiagonal boundary terms has recently been proposed. Using a numerical procedure developed by McCoy et al., we find significant evidence that this solution can yield the complete set of eigenvalues for generic values of the bulk and boundary parameters satisfying one linear relation. Moreover, our results suggest that this solution is practical for investigating the ground state of this model in the thermodynamic limit.Comment: 15 pages, LaTeX; amssymb, amsmath, no figures, 5 tables; v2 contains an additional footnote and a "Note Added"; v3 contains an Addendu

Tailoring the release of drugs having different water solubility by hybrid polymer-lipid microparticles with a biphasic structure

The aim of this study is to investigate the potential of hybrid polymer-lipid microparticles with a biphasic structure (b-MPs) as drug delivery system. Hybrid b-MPs of Compritol & REG;888 ATO as main lipid constituent of the shell and polyethylene glycol 400 as core material were produced by an innovative solvent-free approach based on spray congealing. To assess the suitability of hybrid b-MPs to encapsulate various types of APIs, three model drugs (fluconazole, tolbutamide and nimesulide) with extremely different water solubility were loaded into the polymeric core. The hybrid systems were characterized in terms of particle size, morphology and physical state. Various techniques (e.g. optical, Confocal Raman and Scanning Electron Microscopy) were used to investigate the influence of the drugs on different aspects of the b-MPs, including external and internal morphology, properties at the lipid/polymer interface and drug distribution. Hybrid b-MPs were suitable for the encapsulation of all drugs (encapsulation efficiency > 90 %) regardless the drug hydrophobic/hydrophilic properties. Finally, the drug release behaviors from hybrid b-MPs were studied and compared with traditional solid lipid MPs (consisting of only the lipid carrier). Due to the combination of lipid and polymeric materials, hybrid b-MPs showed a wide array of release profiles that depends on their composition, the type of loaded drug, the drug loading amount and location, providing a versatile platform and allowing the formulators to finely balance the release performance of drugs intended for oral administration. Overall, the study demonstrates that hybrid, solvent-free b-MPs produced by spray congealing are an extremely versatile delivery platform able to efficiently encapsulate and release very different types of drug compounds

Thermodynamics of the 3-State Potts Spin Chain

We demonstrate the relation of the infrared anomaly of conformal field theory with entropy considerations of finite temperature thermodynamics for the 3-state Potts chain. We compute the free energy and compute the low temperature specific heat for both the ferromagnetic and anti-ferromagnetic spin chains, and find the central charges for both.Comment: 18 pages, LaTex. Preprint # ITP-SB-92-60. References added and first section expande

Glutathione-loaded solid lipid microparticles as innovative delivery system for oral antioxidant therapy

The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 µg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment

Spin configurations in hard-soft coupled bilayer systems: from rigid magnet to exchange spring transitions

We investigate equilibrium properties of an exchange-spring magnetic system constituted of a soft layer (e.g. Fe) of a given thickness on top of a hard magnetic layer (e.g. FePt). The magnetization profile M(z) as a function of the atomic position ranging from the bottom of the hard layer to the top of the soft layer is obtained in two cases with regard to the hard layer: i) in the case of a rigid interface (the FePt layer is a single layer), the profile is obtained analytically as the exact solution of a sine-Gordon equation with Cauchy's boundary conditions. Additional numerical simulations also confirm this result. Asymptotic expressions of M(z) show a linear behavior near the bottom and the top of the soft layer. In addition, a critical value of the number of atomic planes in the soft layer, that is necessary for the onset of spin deviations, is obtained in terms of the anisotropy and exchange coupling between the adjacent plane in the soft layer. ii) in the case of a relaxed interface (the FePt layer is a multilayer), the magnetization profile is obtained numerically for various Fe and FePt films thicknesses and applied field.Comment: 10 pages, 9 figures, PRB submitted (12-07-2010

XXZXXZ model as effective Hamiltonian for generalized Hubbard models with broken η\eta-symmetry

We consider the limit of strong Coulomb attraction for generalized Hubbard models with $\eta$-symmetry. In this limit these models are equivalent to the ferromagnetic spin-1/2 Heisenberg quantum spin chain. In order to study the behaviour of the superconducting phase in the electronic model under perturbations which break the $\eta$-symmetry we investigate the ground state of the ferromagnetic non-critical $XXZ$-chain in the sector with fixed magnetization. It turns out to be a large bound state of $N$ magnons. We find that the perturbations considered here lead to the disappearance of the off-diagonal longe-range order.Comment: Results of previous version are generalized, new title, references added. 10 pages, Latex, no figure