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The aim of this study was to assess whether nanofibrous drug mats have potential as delivery systems for poorly water-soluble drugs. Amorphous nanofiber mats from a model poorly water-soluble active pharmaceutical ingredient (API), niflumic acid, together with the polymer excipient, polyvinyl pyrrolidine, were prepared by nozzle-free electrospinning. This technique offers a scalable way for drug formulation, and by increasing the surface area of the drug, the dissolution rate and therefore bioavailability of the API can be improved. In this study, both the amount of the dissolved active ingredient and the dissolution kinetics has been improved significantly when the nanofibrous mats were used in the drug formulation. A 15-fold increase in the dissolved amount of the produced amorphous niflumic acid nanofiber was observed compared to the dissolved amount of the raw drug within the first 15 minutes. Capsule formulation was made by mixing the electrospun nanofibers with a microcrystalline cellulose filler agent. When comparing the dissolution rate of the capsule formulation on the market with the nanofibrous capsules, a 14-fold increase was observed in the dissolved drug amount within the first 15 minutes.

Antibiotic delivery in form of dry powder inhalation has been studied for possible clinical treatment of respiratory tract infection in the recent years. Dry powder inhalation of ciprofloxacin hydrochloride (CIP) assures local antibacterial activity and comfort of easy application. The aim of this work was to test the stability of co-spray-dried CIP in carrier free system. Since the microparticles in the dry powder system are amorphous and do not contain any stabilizer, the effects of temperature and relative humidity (RH) on the physicochemical properties and aerosolization behavior are very important. Therefore investigation of the role of excipients (such as polyvinyl alcohol (PVA), l -leucine (LEU) and hydroxypropyl-beta-cyclodextrin (CD)) on physicochemical stability and aerosolization performance is essential element prior designing the final dosage form. Stability tests (stress and accelerated) were performed at 40 ± 2 °C and 75 ± 5% RH during 6 months. Particle characterization and size measurement – as the most important parameters in aerodynamic behavior – were done by the laser diffraction method, the surface morphology of microparticles was evaluated by scanning electron microscopy (SEM). The physiochemical properties of microparticles were investigated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The resulting aerodynamic behavior of microparticles was studied by Andersen cascade impactor. The overall stability results (against RH and temperature) showed that microparticles containing CIP and LEU alone and in combination with the other excipients were more stable than those containing PVA or CD alone. In relation to fine particle fraction and mass median aerodynamic diameter (determining the aerosolization parameters), it was found that the particle size and particle shape did not show significant changes after the storage. Among the excipients LEU was found to have many advantages, including relatively simple formulation, enhanced aerosolization behaviour, convenient portability and inherently improved stability. Such a composition may serve as an innovative drug delivery system for the local treatment of respiratory tract infection and cystic fibrosis.

The majority of active pharmaceutical ingredients are poorly soluble in water. The rate-determining step of absorption is the dissolution of these drugs. Inclusion complexation with cyclodextrin derivatives can lead to improved aqueous solubility and bioavailability of pharmacons due to the formation of co-crystals through hydrogen-bonding between the components. Inclusion complexes of loratadine were prepared by a convenient new method involving microwave irradiation and the products were compared with those of a conventional preparation method. Dissolution studies demonstrated that the solubility and rate of dissolution of loratadine increased in both of the methods used. The interactions between the components were investigated by thermal analysis and Fourier Transform Infrared studies. The microwave treatment did not cause any chemical changes in the loratadine molecule.

Polymorph screening is currently one of the most important tasks for innovators and for generic companies from both pharmaceutical and intellectual property rights aspects. The different polymorphs have different physicochemical properties, such as the crystal polymorph-dependent solubility which influences the bioavailability. A former drug candidate obtained from Sanofi Pharmaceutical Company (Hungary) was investigated to explore its polymorphism, to distinguish the morphologies generated by analytical examinations and to investigate their relative stabilities. An Avantium Crystal 16 automatic laboratory reactor system was used for the polymorph studies and the studies of their dissolution. Eight polymorphs were obtained by crystallization and transformation methods then characterized by XRPD, DSC, and Raman spectroscopy, scanning electron microscopy, and light microscopy. All the morphologies could be stored in solid without any form transformation for a long time (2 years investigated). According to the first relative stability results, Form I, III, IVa, V, VI, VII are unambiguously metastable forms. Form II and IVb have similar thermodynamic stabilities, that were higher than those of the other polymorphs. A special dissolution medium was developed in which the eight polymorphs showed clear differences in the rate of dissolution.

In this work the biorelevant solubility of four drugs representing different acid-base property, wide range of lipohilicity and low aqueous solubility was studied. The equilibrium solubility of rivaroxaban (non-ionizable), furosemide (acid), papaverine (base) and niflumic acid (ampholyte) was determined in simulated gastric fluid (SGF pH 1.2), in simulated intestinal fluid fasted state (FaSSIF pH 6.5) and fed state (FeSSIF pH 5.0) and their corresponding blank buffers at a temperature of 37 °C using saturation shake-flask method. The concentration was measured by optimized HPLC analysis. The solubilizing effect of bile acid/lipid micelles as additive components of biorelevent media (BRM) is expressed with the solubility ratio (SR: SBRM/Sblank buffer) and the food effect was estimated from SFeSSIF/SFaSSIF coefficient. It was revealed that ionization plays primarily role in solubility of compounds which undergo ionization in BRM. The solubilizing effect in FaSSIF was marginal for the neutral compound (rivaroxaban) and for molecules are anionic at pH 6.5 (furosemide and niflumic acid). The higher concentration of solubilizing agents in FeSSIF improved the solubility of papaverine carrying positive charge and niflumic acid being partially zwitterionic at pH 5.0.

Interest in submicron-sized drug particles has emerged from both laboratory and industrial perspectives in the last decade. Production of crystals in the nano size scale offers a novel way to particles for drug formulation solving formulation problems of drugs with low solubility in class II of the Biopharmaceutical Classification System. In this work niflumic acid nanoparticles with a size range of 200-800. nm were produced by the novel crystallization method, electrospray crystallization. Their properties were compared to those from evaporative and anti-solvent crystallizations, using the same organic solvent, acetone. There is a remarkable difference in the product crystal size depending on the applied methods. The size and morphology were analyzed by scanning electron microscopy and laser diffraction. The structure of the samples was investigated using differential scanning calorimetry, Fourier-transformed infrared spectroscopy and X-ray powder diffraction. The particles produced using electrospray crystallization process were probably changing from amorphous to crystalline state after the procedure. © 2012 Elsevier B.V.

The crystal size, form, wettability and rate of dissolution of a drug are factors limiting its nasal or pulmonary administration. The aim of this work was to achieve an ideal crystal habit, good wettability and the rapid release of meloxicam (MEL), a poorly water-soluble non-steroidal anti-inflammatory drug. The structures of MEL and the carrier-based systems were analysed by differential scanning calorimetry, X-ray diffractometry and Fourier transform infrared spectroscopy. The particle size and morphology were investigated by laser diffraction and SEM analyses. The novelty of this work was the use of a co-spray-drying technique, which resulted in mannitol-based crystalline microcomposites (1-6 μm) containing MEL microcrystals (1-5 μm). The particle size and form of the MEL microcrystals were adjusted by a top-down method. The presence of mannitol (with a MEL:mannitol mass ratio of 1:1) with additives ensured the homogeneous distribution of MEL in the microcomposites with good wettability and rapid release (100% MEL within 5 min).