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

sl(N) Onsager's Algebra and Integrability

We define an $sl(N)$ analog of Onsager's Algebra through a finite set of relations that generalize the Dolan Grady defining relations for the original Onsager's Algebra. This infinite-dimensional Lie Algebra is shown to be isomorphic to a fixed point subalgebra of $sl(N)$ Loop Algebra with respect to a certain involution. As the consequence of the generalized Dolan Grady relations a Hamiltonian linear in the generators of $sl(N)$ Onsager's Algebra is shown to posses an infinite number of mutually commuting integrals of motion

Asymmetric XXZ chain at the antiferromagnetic transition: Spectra and partition functions

The Bethe ansatz equation is solved to obtain analytically the leading finite-size correction of the spectra of the asymmetric XXZ chain and the accompanying isotropic 6-vertex model near the antiferromagnetic phase boundary at zero vertical field. The energy gaps scale with size $N$ as $N^{-1/2}$ and its amplitudes are obtained in terms of level-dependent scaling functions. Exactly on the phase boundary, the amplitudes are proportional to a sum of square-root of integers and an anomaly term. By summing over all low-lying levels, the partition functions are obtained explicitly. Similar analysis is performed also at the phase boundary of zero horizontal field in which case the energy gaps scale as $N^{-2}$. The partition functions for this case are found to be that of a nonrelativistic free fermion system. From symmetry of the lattice model under $\pi /2$ rotation, several identities between the partition functions are found. The $N^{-1/2}$ scaling at zero vertical field is interpreted as a feature arising from viewing the Pokrovsky-Talapov transition with the space and time coordinates interchanged.Comment: Minor corrections only. 18 pages in RevTex, 2 PS figure

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

From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form

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

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

Constructive control of quantum systems using factorization of unitary operators

We demonstrate how structured decompositions of unitary operators can be employed to derive control schemes for finite-level quantum systems that require only sequences of simple control pulses such as square wave pulses with finite rise and decay times or Gaussian wavepackets. To illustrate the technique it is applied to find control schemes to achieve population transfers for pure-state systems, complete inversions of the ensemble populations for mixed-state systems, create arbitrary superposition states and optimize the ensemble average of dynamic observables.Comment: 28 pages, IoP LaTeX, principal author has moved to Cambridge University ([email protected]

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