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The purpose of the present study was to use commercial available polymers like PVP/PEG, soluplus® and kollidon® SR to prepare immediate and sustained release formulations of felodipine by hot melt mixing method. Solid dispersions containing 5, 10, 20 and 30wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130°C and mixing time 10min. As was found from DSC and XDR studies completely amorphous and miscible solid dispersions can be prepared. In all cases a single glass transition was recorded, which is depended from the used drug amount. Hydrogen bonds and the molecular interaction between felodipine and polymer matrices are responsible for the miscibility of prepared formulations. This has as result the substantial enhancement of felodipine release rate in PVP/PEG mixture and due to the high solubility of used polymers immediate release formulations have been prepared. On the contrary, sustained release formulations can be prepared in the case of kollidon SR solid dispersions. The release mechanism of all preparations was studied using different kinetic models. Finally, binding affinity values calculated by molecular docking simulations were used as estimators for predicting long-term drug's physical stability in solid dispersions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.

In the present study predictable pulsatile chronotherapeutics of felodipine (FELO), which is a poorly-water soluble drug, were prepared in the form of two layered tablets. As active core PVP/FELO nanodispersion was used while as effective coating layer different PVP/HPMC blends were added. From dissolution studies of FELO nanodispersions it was revealed that PVP/FELO 90/10 w/w dispersion is an ideal system for pulsatile formulations since the whole amount of FELO is released within the first 30 min. This dissolution enhancement and fast release was attributed to FELO amorphisation, as was found from XRD and DMTA techniques and the effective particle size reduction. Transmission electron microscopy (TEM) studies revealed that FELO creates amorphous nanodispersions into the PVP matrix while particle sizes are directly dependable upon FELO concentration. Drug particles with sizes lower than 150 nm may be the optimal level for a substantial enhancement of FELO dissolution rate. The time of FELO release initiated by the two-layered tablets was adequately adjusted by using different PVP/HPMC blends as coating layer, which is a swellable and erodible barrier. The delaying time of FELO release is directly depended by HPMC concentration and this correlation was mathematically expressed. The significance of these blends is that they are completely miscible over the entire compositional range, thus forming a new matrix with different physicochemical properties, contrary to the initial polymers.

Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the "state of the art" of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to experimentally examine whether poorly water-soluble drugs dispersed in a polymeric matrix exist as amorphous nanodispersions or molecularly dispersed compounds. Felodipine (Felo) dispersed in PVP matrix (solid dispersion) was used as a model drug in this study. Drug/polymer ratios have an impact on the drug average particle size, morphology and dissolution profile while solid dispersions containing up to 50wt% Felo are completely amorphous. SEM, TEM micrographs, and micro-Raman mapping reveal that Felo is dispersed in the form of nanoparticles into the PVP matrix. Due to the high spatial resolution of TEM, it was established that these nanoparticles are not uniform particles, but rather agglomerates of individual particles with sizes smaller than 5–10nm. Moreover, micro-Raman mapping allowed us to observe the size and spatial distribution of domains where the drug existed as molecularly or nanodispersed. Experimental evidence presented in this work contradicts the common belief that amorphous poorly water-soluble drugs exist only in the state of molecular dispersion inside a polymer matrix by showing that both types of dispersions (molecular-level and nanodispersions) can coexist. [Copyright &y& Elsevier]

Abstract: In the present study the release mechanism of the sparingly water-soluble drug felodipine (FELO) from particulate solid dispersions in PVP or PEG was investigated. FT-IR data indicated that a N–H⋯O hydrogen bond is formed between FELO and polymers. The drug–polymer interaction was theoretically studied with the density functional theory with the B3LYP exchange correlation function. The interaction energies have been estimated at −31.8kJ/mol for PVP and −18.8kJ/mol for PEG. Also, detailed vibrational analysis of the complexes showed that the red shift of the N–H bond stretching in FELO molecule due to H-bonding was higher in the FELO–PVP complex than in the FELO–PEG complex. Both the experimental and theoretical data indicated that a stronger interaction of FELO with PVP than with PEG was developed. The interactions of FELO with the polymer appeared to control the physical state (amorphous or crystalline) and the particle size of FELO in the solid dispersions. In the FELO/PVP dispersions, the drug is found as amorphous nanoparticles whereas in FELO/PEG dispersions the drug is dispersed as crystalline microparticles. The size of drug particles in the dispersion was also influenced by drug proportion, with an increase in drug content of the dispersion resulting in increased drug particle size. The particle size of drug, the proportion of drug in the dispersion and the properties of the polymer (molecular weight) appeared to determine the mechanism of drug release from the solid dispersions, which was drug diffusion (through the polymer layer)-controlled at low drug contents and drug dissolution-controlled at high drug contents. In situ DLS measurements indicate that the large initial particles of FELO/PVP and FELO/PEG solid dispersions with low drug content (10–20wt%) are very rapidly decreased to smaller particles (including nanoparticles) during dissolution, leading to the observed impressive enhancement of FELO release rate from these dispersions. [Copyright &y& Elsevier]

Abstract: Solid dispersion systems are widely investigated for the dissolution enhancement of poorly water soluble drugs. Nevertheless, very limited commercial use has been achieved due to the poor predictability of such systems caused by the lack of a basic understanding of the dissolution optimization mechanism. In the present study an investigation of the release mechanism is performed for solid dispersion systems composed by polyvinylpyrrolidone (PVP) and felodipine (FEL), based on a correlation of their hydrophilicity with the intensity of interactions. The existing interactions were evaluated by using NMR and UV spectroscopy while molecular simulation techniques were also enabled. It was found that the interactions that take place correspond to the creation of hydrogen bonds. The correlation between the intensity of interactions and the concentration of PVP in the matrix showed a sigmoid function. The interactions are impressively increased for polymer concentration exceeding 75% (w/w). This phenomenon was well explained by using the molecular simulation technique. A similar sigmoid pattern was found for the function between dissolution profiles and polymer concentration in the matrix, indicating that the intensity of interactions promotes the dissolution enhancement. Investigation of the solubility and the particle size distribution of FEL in the binary system appeared to have similar behaviour indicating that the interactions affect the release profile through these two factors. The hydrophilicity of PVP does not significantly affect this enhancement as the contact angle was found to be linear to PVP concentration. Microscopic observation of the dissolution behaviour showed that FEL remains in fine dispersion in aqueous solution, verifying the release mechanism. [Copyright &y& Elsevier]

Abstract: Polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG) solid dispersions with Felodipine or Hesperetin having up to 20wt% drug were prepared using solvent evaporation method. Solid dispersions in comparison with their physical mixtures were studied using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), scanning electron microscopy (SEM) and hot stage polarizing light microscopy (HSM). PVP formulations with low drug load proved to be amorphous, since no crystalline Felodipine or Hesperetin drugs were detected using DSC and WAXD. Low and fast heating rates were applied for DSC study, to prevent changes in the samples caused during heating. Similarity between results of WAXD and DSC was also found in the case of physical mixtures, where the drug was in the crystalline state. However, though specific tests showed the high sensitivity of the DSC technique, it was difficult to arrive to reliable results for PEG solid dispersions or physical mixtures with low drug content by DSC, even by high heating rates. Crystalline drug could not be detected by DSC, leading to erroneous conclusions about the physical state of the drug, in contrast to WAXD. On the other hand, HSM proved the presence of small drug particles in the solid dispersions with PEG and the dissolution of the drug in the melt of PEG on heating. In such systems, in which a polymer with low melting point is used as drug carrier, DSC is inappropriate technique and must be used always in combination with HSM. The coupling of WAXD with thermal analysis, allowed complete physicochemical characterization and better understanding which is essential for a first prediction of dissolution characteristics of such formulations. [Copyright &y& Elsevier]