Structure Of Solid Dispersions Research Articles

Experimental and Numerical Study of the Discharge Performance of Particle-Laden Turbulent Flow

In the marine fire suppression system, continuous delivery of dry chemical powder to the fire source with long powder discharge range and high dispersion concentration is essential. The work is devoted to experimental and numerical studies of the flow characteristics of the dry chemical powder jet from a horizontal injector with a wide range of Stokes numbers between 6 to 30 and Reynolds numbers between 4792 to 23,960 by considering the effect of gravitational acceleration. A CFD-based Eulerian–Eulerian multiphase model combined with Standard k-ω turbulence model was used to predict flow characteristics of particle-laden jet using dimensionless numbers, including the solid volume fraction, the normalized velocity magnitude, and the turbulent viscosity ratio. Experimental studies have been carried out for three different inflow velocities (2.06, 2.45, and 2.81 m/s). The results indicate that the particle density plays a significant role in the dispersion of the particles in the radial and axial directions. The transition from U-shaped to V-shaped solid dispersion structure on the ground can be captured with the increase of particle density. Moreover, the higher level turbulence intensity enhances the solid dispersion concentration. Finally, it was found that the Portland cement powder exhibits better discharge performance in terms of solid discharge range and dispersion concentration in comparison with other dry powders. These results have implications in the design of powder-based fire suppression system. Further studies should aim to the in-depth research on the fire extinguishing mechanism of the Portland cement powder, especially the fire suppression effectiveness and thermal decomposition process.

Studies on phase diagram, thermodynamic stability and interfacial structure of solid dispersions of phenothiazine-adipic acid drug system

In the present communication phase diagram, thermodynamic quantities, stability and interface structure of phenothiazine (PT)-adipic acid (AA) binary system have been reported. Eutectics (E1, E2) at 0.631 and 0.868 mole fraction of PT and addition compounds (A 1:1, A 4:1) are formed in the system. Partial and integral thermodynamic quantities such as excess Gibbs energy (gE), excess enthalpy (hE) and excess entropy (sE) of eutectic and non-eutectic mixtures were also calculated using activity coefficient data. The positive value of excess Gibbs free energy indicates deviation from ideal behavior which refers stronger association between like molecules during formation of binary mix. The positive value of Gibbs free energy of mixing (ΔGM) suggests the mixing for eutectic and non-eutectic is non-spontaneous. The size of critical nucleus at different undercoolings has been found in nanoscale, which may lead a big challenge in pharmaceutical world.

Understanding the mechanism of dissolution enhancement for poorly water-soluble drugs by solid dispersions containing Eudragit® E PO

In this paper, we intended to understand the mechanism of dissolution enhancement for poorly water-soluble drugs by amorphous solid dispersions containing EUDRAGIT® E PO (EPO). Equilibrium solubility enhancement for three model drugs including ibuprofen, felodipine and bifendate were tested in acidic solutions containing different concentrations of EPO. Three model drugs were prepared into amorphous solid dispersions by hot melt extrusion with EPO. Results showed that EPO can substantially solubilize model drugs in acidic solution to 20–300 fold of their thermodynamic solubilities. Linear solubilizing relationships between EPO and drugs were achieved for all three drugs. It was found that amorphous solid dispersions with drug loadings below solubilizing range showed no recrystallization in dissolution tests whereas drug concentration reduction was seen in dissolution tests when drug loadings were above the solubilizing range. By combining the results from dynamic laser scattering, critical micelle concentration (CMC) and morphology studies, it was confirmed that EPO can form micelles in acidic solution, and the CMC value was estimated as 0.99 μg/ml. In conclusion, the dissolution enhancement for poorly water-soluble drugs by amorphous solid dispersions containing EPO was combined contribution from both the physical structure of solid dispersions and the solubilizing effect of EPO.

Development of the methodological approach of obtaining preparations based on solid dispersions

Nowadays, the innovative direction of pharmaceutical development is the application of methods to increase the biopharmaceutical efficiency and safety of the use of already existing APIs, including method of incorporating them into solid dispersions in which the substance molecules are included in the supramolecular formations by forming non-covalent bonds by excipients. Today, the preparation of solid dispersions is considered as the most effective way of increasing oral bioavailability, in which dissolution of the carrier facilitates the release of API with its rapid solubilization. According to the literature, it is established that today there is only an empirical approach to obtaining solid dispersions. The aim of the work was the formulation of the main approaches to the development of preparations on the basis of solid dispersions, taking into account the current trends in the development of the composition and technology of preparations with sparingly soluble active pharmaceutical ingredients. Materials and methods. To develop a methodological approach, external situational content analysis of applied methods for increasing the bioavailability of active pharmaceutical ingredients used in the manufacture of solid dosage forms was used. Results. In the course of accomplishing this goal, a classification of the types of solid dispersions was proposed depending on the structure and method of production, an algorithm was developed for choosing a method for obtaining a solid dispersion, taking into account the physico-chemical properties of the active pharmaceutical ingredients, which can be used in the technological process to increase their bioavailability. Critical components were also found in the development of solid dispersions. Conclusions. Taking into account the physicochemical properties of the active pharmaceutical ingredients, was chosen an algorithm for selecting a method for preparing solid dispersions that can be used in the process to improve their bioavailability. Based on the results of the analysis of the literature data and our own research of the physico-chemical characteristics of the active pharmaceutical ingredients and excipients, type of the solid dispersion structure, the type of solvent and carrier, a methodological approach to the preparation of solid dispersions is proposed, the use of which will optimize the development of solid dosage forms

Investigating the molecular structures of solid dispersions by the simulated annealing method

Knowledge of the molecular structures of solid dispersions is vital, yet, despite thousands of reports in this area, it remains unclear. The aim of this research is to investigate the molecular structure of solid dispersions with hot melt preparation method by the simulated annealing method. Simulation results showed linear polymer chains form the random coils under heat and the drug molecules stick on the surface of polymer coils, while drug molecules are dispersed molecularly but irregularly within the amorphous low molecular weight carriers. This research presents more reasonable molecular images of solid dispersions than the existed theory.

Dissolution properties of control released solid dispersion of carvedilol with HPMC and Eudragit RS

In this study, solid dispersion for carvedilol was prepared by using spray-drying method. Solid dispersions were formulated with carvedilol and Eudragit RS and hydroxypropyl methylcellulose to control the dissolution rates of carvedilol. Scanning electron microscope was used to analyze surface of solid dispersion samples. Differential scanning calorimetry and powder X-ray diffraction were used to analyze the crystallinity of solid dispersions. Fourier transform infrared spectroscopy was used to analyze the change in chemical structure of solid dispersions. The release behavior of solid dispersion analyzed at simulated gastric fluid (pH 1.2) in in vitro study. The dissolution rate of carvedilol was higher than active pharmaceutical ingredient. In conclusion, we can control the dissolution rate by solid dispersion using biomedical polymers.

Analysis of Amorphous Solid Dispersions Using 2D Solid-State NMR and 1H T1 Relaxation Measurements

Solid-state NMR (SSNMR) can provide detailed structural information about amorphous solid dispersions of pharmaceutical small molecules. In this study, the ability of SSNMR experiments based on dipolar correlation, spin diffusion, and relaxation measurements to characterize the structure of solid dispersions is explored. Observation of spin diffusion effects using the 2D (1)H-(13)C cross-polarization heteronuclear correlation (CP-HETCOR) experiment is shown to be a useful probe of association between the amorphous drug and polymer that is capable of directly proving glass solution formation. Dispersions of acetaminophen and indomethacin in different polymers are examined using this approach, as well as (1)H double-quantum correlation experiments to probe additional structural features. (1)H-(19)F CP-HETCOR serves a similar role for fluorinated drug molecules such as diflunisal in dispersions, providing a rapid means to prove the formation of a glass solution. Phase separation is detected using (13)C, (19)F, and (23)Na-detected (1)H T(1) experiments in crystalline and amorphous solid dispersions that contain small domains. (1)H T(1) measurements of amorphous nanosuspensions of trehalose and dextran illustrate the ability of SSNMR to detect domain size effects in dispersions that are not glass solutions via spin diffusion effects. Two previously unreported amorphous solid dispersions involving up to three components and containing voriconazole and telithromycin are analyzed using these experiments to demonstrate the general applicability of the approach.

Surface composition and contact angle relationships for differently prepared solid dispersions

Solid dispersions are promising drug delivery forms which offer the possibility to disperse a hydrophobic drug in a hydrophilic matrix and thereby improve the dissolution behavior and the bioavailability of the drug. One important aspect and a prerequisite in understanding the drug dissolution mechanism from solid dispersions is a better analytical monitoring of the solid dispersion surface properties, such as powder surface composition and water adsorption properties. In this paper, we have considered chemical and structural surface analysis data for solid dispersions processed by spray drying or roto-evaporation and compared these data with information obtained by contact angle measurements. Firstly, we establish the usefulness and suitability of X-ray photoelectron spectroscopy (XPS) for determination of surface chemical composition and scanning electron microscopy (SEM) for determining the structure of solid dispersions composed of different types of carriers, drugs and drug concentrations. Secondly, we measure contact angles of solid dispersions to describe wettability, to finally establish a link between the surface chemical composition, the powder structure and the wetting behavior. These experimental methods offer a rapid screening tool for the selection of carrier, drug concentration and/or process in early development. In addition, they provide a useful tool for investigating structural aspects of solid dispersions which have intrinsic relevance for drug dissolution and stability.

In Vivo Evaluation of Two Novel Controlled-Release Nitrendipine Formulations

The objective of this work is to assess two novel controlled-release nitrendipine formulations, i.e., sustained-release nitrendipine microspheres having solid dispersion structure and a novel pH-dependent gradient-release delivery system for nitrendipine in healthy male volunteers, which were prepared by current authors. Domestic commercial nitrendipine tablets and Baypress™ nitrendipine tablets were employed as reference formulations. In a randomized, single-dose, fasting-state, crossover study design with a 1-week washout period, each subject received a 40-mg nitrendipine formulation. Plasma samples were collected over a 25-hour period after oral administration and were analyzed by a validated method using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined using a noncompartmental analysis. The results provided evidence that the time to maximum plasma concentration of two novel controlled-release nitrendipine formulations were statistically significant prolonged in comparison with that of Baypress™ nitrendipine tablets. The relative bioavailabilities of test formulations were intensively improved compared with the domestic nitrendipine tablets, while the ratio is in a range of 80–120% in comparison with Baypress™ nitrendipine tablets. It is concluded that the two types of controlled-release systems are feasible for improving the dissolution rate of nitrendipine and obtaining a long-acting in vivo as well.

Effect of three types of additives in poor solvent on preparation of sustained-release nitrendipine microspheres by the quasi-emulsion solvent diffusion method

Sustained-release microspheres of nitrendipine with hydroxypropylmethylcellulose phthalate (HP-55) having a solid dispersion structure were prepared by using the quasi-emulsion solvent diffusion method of the spherical crystallization technique. To investigate the effect of the additives in poor solvent on the preparation of the nitrendipine microspheres, three types of additives, i.e. C 12 H 25 ,NaO 4 S (sodium dodecyl sulfate), NaOH, and KH 2 PO 4 NaOH mixture, were chosen. The resultant microspheres were evaluated with respect to their recoveries, micromeritic properties and release rates. The mechanisms involved in the effect of different poor solvents on formation of the microspheres are discussed. The sustained-release nitrendipine microspheres could not be prepared without using any additives added to the poor solvent. The additives dissolved in poor solvent could affect the micromeritic properties and the release profiles of the resultant microspheres. On increasing the amount of additives, the total recoveries of microspheres were increased and the average diameter of the microspheres was reduced. It was found that a dissociation of HP-55 in poor solvent contributed to the formation of sustained-release nitrendipine microspheres. The release rate of the microspheres prepared with sodium dodecyl sulfate aqueous solution was slower than that of the other two additives, due to the more dense structure formed. Since HP-55, a pH-dependent polymer, was formulated in the present microspheres, the pH value of dissolution medium was one of critical factors to determine the dissolution rate.

Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

To improve the bioavailability of nitrendipine microspheres, a sustained-release microspheres having solid dispersion structure were prepared in one step. Two types of polymer, i.e. solid dispersing and sustained-release polymers, were employed to prepare the microspheres by the spherical crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled as desired by adjusting the combination ratio of dispersing agents to retarding agents. The results of X-ray diffraction and differential scanning calorimetry analysis indicated that the crystalline form of nitrendipine was disordered, suggesting that nitrendipine was highly dispersed in microspheres, so as amorphous state. The release profiles and content of the microspheres stored at a temperature of 40°C and a relative humidity of 75% were unchanged during 3 months of accelerating condition of storage. And the relative bioavailability of the sustained-release microspheres compared with the Baypress™ tablets and the conventional tablets was 107.78% and 309.82%. In conclusion, the sustained-release microspheres with solid dispersion structure improved the bioavailability of the water insoluble drug and prolonged the T max value.

Solid state properties of pure UC-781 and solid dispersions with polyvinylpyrrolidone (PVP K30).

The purpose of this study was to elucidate the physical structure of solid dispersions of the antiviral agent UC-781 (N-[4-chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furancarbothioamide) with polyvinylpyrrolidone (PVP K30). Solid dispersions were prepared by coevaporating UC-781 with PVP K30 from dichloromethane. The physicochemical properties of the dispersions were evaluated in comparison with the physical mixtures by differential scanning calorimetry (DSC), X-ray powder diffraction, and FT-IR spectroscopy. We investigated the single crystal structure of pure UC-781. The data from single crystal analysis showed that UC-781 crystallized with orthorhombic symmetry in the space group Pcab. Its cell parameters were found to be; a = 8.1556(7) A,b = 17.658(2) A and c = 23.609(2) A; the unit cell was made up of eight molecules of UC-781. The molecules formed intermolecular hydrogen bonds between NH and thio groups, and were packed in a herringbone-like structure. The data from X-ray powder diffraction showed that crystalline UC-781 was changed into the amorphous state by co-evaporating it with PVP K30. From differential scanning calorimetry analysis, UC-781 peaks were observed in the DSC curves of all physical mixtures, while no peaks corresponding to the drug could be observed in the solid dispersions with the same drug composition up to the concentration of 50% w/w. The data from FT-IR spectroscopy showed the distortions and disappearance of some bands from the drug, while other bands were too broad or significantly less intense compared with the physical mixtures of the crystalline drug in PVP K30. Furthermore, the results from IR spectroscopy demonstrated that UC-781 interacted with PVP K30 in solid dispersions through intermolecular H-bonding.

An investigation into the production of paracetamol solid dispersions in PEG 4000 using hot stage differential interference contrast microscopy

The melting and crystallisation behaviour of paracetamol dispersions in polyethylene glycol (PEG) 4000 has been studied using differential interference contrast microscopy fitted with a hot stage. The effects of thermally cycling physical mixes of the two components have been studied with particular reference to the effects of the presence of molten PEG 4000 on the melting behaviour of the model drug. The effects of the drug particle size, the maximum temperature of heating and the holding time at the maximum temperature on the solid dispersion structure have been investigated, with profound changes in structure being observed depending on the manufacturing protocol used. In particular, higher maximum temperatures and holding times with lower drug particle sizes promoted greater dissolution of the drug into the molten PEG. In the majority of systems observed, the remaining paracetamol particles simply persisted as the system was cooled. However, for certain systems, involving high drug loadings and extended holding times and temperatures in the liquid state, the drug recrystallised over a 24-h period to form a fine dispersion within the carrier. The study has therefore demonstrated the usefulness of hot stage microscopy as a method of directly observing the processes involved during the manufacture of solid dispersions and has also indicated that changing the manufacturing protocol may have a profound effect on the structure of the dispersion.

Structure of solid dispersions in the system polyethylene glycol-griseofulvin with additions of sodium dodecyl sulphate

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin were prepared by the melting method. Samples were also prepared with 10% w/w of the anionic surfactant sodium dodecyl sulphate (SDS) added to the melt. Phase analysis was performed by X-ray powder diffraction and investigation of the short-range structure by 13C-CP/MAS solid-state NMR. In the samples without the added surfactant, a solid particulate dispersion of griseofulvin in PEG is obtained. The periodic structure of the pure phases is retained and so is the local structure as seen by NMR. When a surfactant is added to the dispersion a solid molecular dispersion i.e., a solid solution, is formed. The interaction between the environment and certain carbons in griseofulvin and SDS is evident. Both hydrophilic and hydrophobic parts of the molecules are influenced in a significant way. The solid solution of griseofulvin in PEG obtained on addition of SDS seems to depend on an interaction between the polymer and SDS in aggregates (micelles). These aggregates can bind griseofulvin in a molecular form at the surface or in the interior of the aggregate.