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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 30 wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130 °C and mixing time 10 min. 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. [ABSTRACT FROM AUTHOR]

Abstract: Polymeric matrices of ι-, κ- and λ-carrageenans and ι-, κ- and λ-carrageenans blends, prepared by simple mixing and by solvent evaporation technique, have been tested for controlled release delivery of Tolterodine l-Tartrate. X-ray diffraction (XRD), infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and viscometry measurements showed that although all weight ratios of carrageenans blends were immiscible, carrageenans formed complexes with the drug through hydrogen bonding. In solid dispersions formulations although the drug was almost immediately dissolved (due to its amorphous character), an amount remained absorbed into polymer matrix and was not released, probably due to hydrogen bonding. When physical mixtures of pure carrageenans and Tolterodine l-Tartrate were prepared, release rate was slower and when λ-carrageenan was used, an almost controlled release formulation was achieved. However, real controlled release formulations were achieved only when physical mixtures of ι-/λ-carrageenans and Tolterodine were used. Thus, the combination of different types of carrageenans could change the carrier’s behaviour. [Copyright &y& Elsevier]

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: 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]

In the present study, solid dispersion systems of felodipine (FEL) with polyvinylpyrrolidone (PVP) were developed, in order to enhance solid state stability and release kinetics. The prepared systems were characterized by using Differential Scanning Calorimetry, X-Ray Diffraction, and Scanning Electron Microscopy techniques, while the interactions which take place were identified by using Fourier Transformation-Infrared Spectroscopy. Due to the formation of hydrogen bonds between the carbonyl group of PVP and the amino groups of FEL, transition of FEL from crystalline to amorphous state was achieved. The dispersion of FEL was found to be in nano-scale particle sizes and dependent on the FEL/PVP ratio. This modification leads to partial miscibility of the two components, as it was verified by DSC and optimal glass dispersion of FEL into the polymer matrix since no crystalline structure was detected with XRD. The above deformation has a significant effect on the dissolution enhancement and the release kinetics of FEL, as it causes the pattern to change from linear to logarithmic. An impressive optimization of the dissolution profile is observed corresponding to a rapid release of FEL in the system containing 10% w/w of FEL, releasing 100% in approximately 20 min. The particle size of dispersed FEL into PVP matrix could be classified as the main parameter affecting dissolution optimization. The mechanism of such enhancement consists of the lower energy required for the dissolution due to the amorphous transition and the fine dispersion, which leads to an optimal contact surface of the drug substance with the dissolution media. The prepared systems are stable during storage at 40 ± 1°C and relative humidity of 75 ± 5%. Addition of sodium docusate as surfactant does not affect the release kinetics, but only the initial burst due to its effect on the surface tension and wettability of the systems. [ABSTRACT FROM AUTHOR]

Abstract: The effect of plasticizer’s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous. Furthermore, a single Tg recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG’s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices. All prepared solid dispersion showed long-term physical stability (18months in room temperature). The extent of interaction between mixture components was verified using Fox and Gordon–Taylor equations. Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability. [Copyright &y& Elsevier]

Abstract: In the present study, the efficiency of PVP/PEG200 mixtures as appropriate carries for the preparation of solid dispersions by melt mixing was evaluated. Felodipine (FELO) was used as a poorly water soluble model drug. The effect of several melt mixing parameters, (PVP/PEG ratio, time and temperature of melt mixing, and drug content), on the physical state of FELO and the dissolution characteristics of the dispersions were investigated. DSC, XRD, and SEM analysis revealed that in all cases, amorphous drug nanodispersions were prepared. This was attributed to the increased miscibility of the PVP–FELO system, induced by the presence of PEG200, which acted as plasticizer. FT-IR analysis showed hydrogen bonding between FELO (h name="sbnd" />H) and the PVP carrier (h name="dbnd" />O). The release rate of the drug depends mainly on the drug content and is higher in solid dispersions with low drug content and ratio of carrier to plasticizer (PVP/PEG200). The melt mixing variations (time and temperature of mixing) had lower impact on FELO release rate. Finally, artificial neural networks, used to correlate the examined formulation and process variables of hot melt mixing with dissolution parameters, showed good prediction ability. [Copyright &y& Elsevier]

Abstract: Polymeric matrices of chitosan (CS), 2-hydroxyethyl starch (HES) and their blends prepared by solvent evaporation technique, have been tested as sustained release hydrogels of ropinirole drug. X-Ray diffraction (XRD), infrared spectroscopy (FT-IR) and viscometry measurements showed that the two polymers can form miscible blends. This miscibility is owed to formed hydrogen bonds taking place between the reactive groups of CS and HES and one glass transition is recorded in all blends. Neat polymers were used to prepare solid dispersion formulations with ropinirole drug. It was found that drug was released immediately within 15–30min from HES while the release was slower from CS matrix. Completely different were the release rates from ropinirole with physical mixtures using neat polymers and their blends. Due to the different solubility and swelling behaviour of CS and HES the release rates showed a sustained profile from the blends containing high amounts of CS. [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]