Phase Diagrams of Polymer-Dispersed Liquid Crystal Systems of Itraconazole/Component Immiscibility Induced by Molecular Anisotropy.

Liquid crystalline (LC) materials and their nonmedical applications have been known for decades, especially in the production of displays; however, the pharmaceutical implications of the LC state are inadequately appreciated, and the misunderstanding of experimental data is leading to possible errors, especially in relation to the physical stability of medicines. The aim of this work was to study LC phases of itraconazole (ITZ), an azole antifungal active molecule, and for the first time, to generate full thermodynamic phase diagrams for ITZ/polymer systems, taking into account isotropic and anisotropic phases that this drug can form. It was found that supercooled ITZ does not form an amorphous but a vitrified smectic (vSm) phase with a glass transition temperature of 59.

Freeze drying of polyelectrolyte complex nanoparticles: Effect of nanoparticle composition and cryoprotectant selection.

This work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG).

Amorphous Polymeric Drug Salts as Ionic Solid Dispersion Forms of Ciprofloxacin.

Ciprofloxacin (CIP) is a poorly soluble drug that also displays poor permeability. Attempts to improve the solubility of this drug to date have largely focused on the formation of crystalline salts and metal complexes. The aim of this study was to prepare amorphous solid dispersions (ASDs) by ball milling CIP with various polymers.

Cocrystal habit engineering to improve drug dissolution and alter derived powder properties.

Objectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM : 4-ASA cocrystals with different habits to investigate the effect on dissolution, and the derived powder properties of flow and compaction.

Methods: Cocrystals were prepared in a 1 : 1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray drying (habit IV).

Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility.

In this study, a comparison of different methods to predict drug-polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug-polymer solubility at 25 °C was predicted using the Flory-Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate).

Self-assembled hyaluronate/protamine polyelectrolyte nanoplexes: synthesis, stability, biocompatibility and potential use as peptide carriers.

This work investigates a new type of polyelectrolyte complex nanocarrier composed of hyaluronic acid (HA) and protamine (PROT). Small (approximately 60 nm) and negatively charged nanoparticles (NPs) with a polydispersity index of less than 0.2 were obtained with properties that were dependent on the mixing ratio, concentration of polyelectrolytes and molecular weight of HA.

Chondroitin-based nanoplexes as peptide delivery systems--Investigations into the self-assembly process, solid-state and extended release characteristics.

A new type of self-assembled polyelectrolyte complex nanocarrier composed of chondroitin (CHON) and protamine (PROT) was designed and the ability of the carriers to bind salmon calcitonin (sCT) was examined. The response of sCT-loaded CHON/PROT NPs to a change in the properties of the liquid medium, e.g.

Molecular structure studies of (1,2)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol.

The single enantiomer (1,2)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (), has recently been synthesized and isolated from its corresponding diastereoisomer (). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy.

Polymorphism in sulfadimidine/4-aminosalicylic acid cocrystals: solid-state characterization and physicochemical properties.

Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid-state characterization of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time.

Heat induced evaporative antisolvent nanoprecipitation (HIEAN) of itraconazole.

Itraconazole (ITR) is an antifungal drug with a limited bioavailability due to its poor aqueous solubility. In this study, ITR was used to investigate the impact of nanonisation and solid state change on drug's apparent solubility and dissolution. A bottom up approach to the production of amorphous ITR nanoparticles (NPs), composed of 100% drug, with a particle diameter below 250 nm, using heat induced evaporative antisolvent nanoprecipitation (HIEAN) from acetone was developed.

Dry powders for oral inhalation free of lactose carrier particles.

Dry powder inhaler (DPI) products have traditionally comprised a simple formulation of micronised drug mixed with a carrier excipient, typically lactose monohydrate. The presence of the carrier is aimed at overcoming issues of poor flowability and dispersibility, associated with the cohesive nature of small, micronised active pharmaceutical ingredient (API) particles. Both the powder blend and the DPI device must be carefully designed so as to ensure detachment of the micronised drug from the carrier excipient on inhalation.

Observation of highly decoupled conductivity in protic ionic conductors.

Ionic liquids (ILs) are key materials for the development of a wide range of emerging technologies. Protic ionic liquids, an important class of ILs, have long been envisioned as promising anhydrous electrolytes for fuel cells. It is well known that in comparison to all other cations, protons exhibit abnormally high conductivity in water.

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution.

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate.

Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability.

In order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms.

Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid.

Multi-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained.

Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery.

In a number of pulmonary diseases, patients may develop abnormally viscous mucus reducing drug efficacy. To increase budesonide diffusion within lung fluid, we developed nanoporous microparticles (NPMPs) composed of budesonide and a mucokinetic, ambroxol hydrochloride, to be inhaled as a dry powder. Budesonide/ambroxol-HCl particles were formulated by spray drying and characterised by various physicochemicals methods.

Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles--Part II. Physicochemical characterisation of spray-dried materials.

Objectives: In this work we investigated the residual organic solvent content and physicochemical properties of spray-dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts.

Methods: The powders were characterised by thermal, X-ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl-Fischer titration and gas chromatography.

Impact of process variables on the micromeritic and physicochemical properties of spray-dried porous microparticles, part I: introduction of a new morphology classification system.

Objectives: This work investigated the impact of spray drying variables such as feed concentration, solvent composition and the drying mode, on the micromeritic properties of chlorothiazide sodium (CTZNa) and chlorothiazide potassium (CTZK).

Methods: Microparticles were prepared by spray drying and characterised using thermal analysis, helium pycnometry, laser diffraction, specific surface area analysis and scanning electron microscopy.

Key Findings: Microparticles produced under different process conditions presented several types of morphology.

Exploring the assembly process and properties of novel crosslinker-free hyaluronate-based polyelectrolyte complex nanocarriers.

The aim of this work was to study the formulation of pharmaceutically relevant polyelectrolyte complex nanoparticles (NPs) composed of hyaluronic acid (HA) and chitosan (CS) containing no crosslinkers. The influence of polymer mixing ratio, concentration and molecular weight as well as the type of counterion in chitosan salt on properties of the resulting NPs was examined. Formulations and their components were studied by laser light scattering, viscosity, infrared spectroscopy and microscopy.

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability.

High-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.

Biopharmaceutical characterization of ciprofloxacin HCl-ferrous sulfate interaction.

The ciprofloxacin-iron interaction, resulting in a lower bioavailability, is well documented in vivo; however, a mechanistic explanation supported by experimental data of this interaction is missing. In the present study, ciprofloxacin hydrochloride (HCl) and ferrous sulfate interaction was simulated in vitro by performing solubility and dissolution studies in the reactive media containing ferrous sulfate. Characterization of the precipitate formed indicated its probable chemical structure as Fe(SO(4) (2-) )(2) (Cl(-) )(2) (ciprofloxacin)(2) × (H(2) O)(n) , where n is up to 12 molecules of water.

Solid-state characterization of novel active pharmaceutical ingredients: cocrystal of a salbutamol hemiadipate salt with adipic acid (2:1:1) and salbutamol hemisuccinate salt.

The production of salt or cocrystalline forms is a common approach to alter the physicochemical properties of pharmaceutical compounds. The goal of this work was to evaluate the impact of anion choice (succinate, adipate, and sulfate) on the physicochemical characteristics of salbutamol forms. Novel crystals of salbutamol were produced by solvent evaporation: a cocrystal of salbutamol hemiadipate with adipic acid (salbutamol adipate, SA), salbutamol hemisuccinate tetramethanolate (SSU.

Preparation and characterisation of novel chlorothiazide potassium solid-state salt forms: Intermolecular self assembly suprastructures.

Chlorothiazide (CTZ) is a poorly soluble diuretic agent. The aim of the present work was to produce and characterise a potassium salt form of chlorothiazide which has the potential advantages of improved aqueous solubility and potassium supplementation. A number of novel potassium salt forms of CTZ (CTZK) were prepared: CTZK monohydrate (form I), CTZK dihydrate (form II), anhydrous CTZK (form III), CTZK monohydrate hemiethanolate (form IV) and a desolvate of CTZK monohydrate hemiethanolate (form V).