Preformulation study of nicergoline solid dispersions

Nicergoline, a semisynthetic ergot derivative, which, in its crystalline state, is insoluble in water, was dispersed in polyvinylpyrrolidone K30 (PVP K30) to improve drug particle dissolution. Preformulation studies were carried out initially by differential scanning calorimetry and X-ray powder diffraction in order to predict the conditions and the possibility to actually obtain solid dispersions by mixing the two components at different proportions. Solid dispersions were finally prepared by dissolving nicergoline and PVP K30 in chloroform that was next evaporated under reduced pressure. Under these conditions, an amorphous powder was recovered in every proportion of the two components. Nicergoline demonstrated to be physically and chemically stable for 1 year. The dissolution studies revealed a very high dissolution rate of nicergoline from solid dispersions only lower than the pure amorphous form. This is the consequence of the molecular dispersion of nicergoline in the polymer that enhances the rate of drug release from the polymer.     

Mechanochemical preparation of drug carrier solid dispersions

The method of mechanical activation was used to obtain solid-state dispersions of some drugs in polyvinylpyrrolidone, polyethylene glycol and talc as carriers. Solid dispersions obtained by mechanical activation were found to have higher apparent solubilities and dissolution rates than mechanically activated drugs or their physical or eutectic mixtures with carriers used. It was shown by IR-spectroscopy and fluorescence measurements that mechanical treatment gave rise to an interaction between components which was apparently responsible for the solubilization effects observed.     

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.     

Methods for obtaining solid dispersions of drugs and their properties

The possibility of improving the solubility of drugs by obtaining solid dispersions (SDs) with polymers is demonstrated. The solubility of these SDs is dependent both on the nature of drug and polymer and on the conditions of their preparation. IR spectroscopy of the obtained SDs and the analysis of results found in literature indicate that inclusion complexes are formed within them.

     

Characterization of solid dispersions of rofecoxib using differential scanning calorimeter

Summary Solid dispersions were prepared to enhance the dissolution rate of rofecoxib. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used for the characterization of solid dispersions of polyvinyl pyrrolidone (PVP):talc:drug (3:1:1) and hydroxypropyl methylcellulose (HPMC):talc:drug (4:1:1). The DSC study indicated that PVP solid dispersion showed formation of fusion solution while HPMC solid dispersion showed no intermolecular fusion during the preparation of solid dispersions by spray dry process. The dissolution profiles and the calculated times for 75 and 90% drug release showed that dissolution rate of rofecoxib was improved in solid dispersions as compared to pure drug and physical mixtures. The DSC and XRD were successfully employed to find out the crystalline state of drug in the both solid dispersions. PVP solid dispersion gave better dissolution rate than HPMC solid dispersion. The drug was transformed from crystalline to amorphous form in PVP solid dispersion which was further conformed by XRD and DSC. The PVP:talc:drug solid dispersion can be used for the dissolution enhancement and thereby bioavailability of rofecoxib.     

Thermal analysis study of flavonoid solid dispersions having enhanced solubility

Purposes of this paper were to prepare and study new drug delivery systems for both flavanone glycosides and their aglycones based on solid-dispersion systems. These compounds are poor water soluble drugs, so an enhancement of their dissolution is a high priority. Solid-dispersion systems were prepared using PVP, PEG and mannitol as drug carrier matrices. Characterizations of these dispersions were done by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). The glass transition (T_g) temperature of PVP was only recorded in the DSC thermograms of PVP solid-dispersions of both flavanone glycosides and their aglycones, while in case of PEG and mannitol solid-dispersions endotherms of both glycosides and aglycones were noticed with low peak intensity, indicating that high percent of drug is in amorphous state. The XRD patterns of all PVP solid-dispersions of aglycones show typical amorphous materials, but XRD patterns of their glycosides reveal the presence of crystalline material. However, in all solid dispersions shifts in T_g of PVP as well as T_m of PEG were observed, indicating the existence of some interactions between drugs and matrices. SEM and TEM microscopy revealed that PVP/aglycone flavanone compounds are nanodispersed systems while all the other solid dispersions are microcrystalline dispersions. The solubility of both flavanone glycosides and their aglycones was directly affected by the new physical state of solid dispersions. Due to the amorphous drug state or nano-dispersions in PVP matrices, the solubility was enhanced and found to be 100% at pH 6.8 in the nano-dispersion containing 20 mass% of aglycones. Also solubility enhancement was occurred in solid dispersions of PEG and mannitol, but it was lower than that of PVP nano-dispersions due to the presence of the drug compounds in crystalline state in both matrices.     

Use of Gemini surfactants to stabilize TiO2 P25 colloidal dispersions

Photocatalytically active TiO₂ P25 nanoparticles, widely used for practical applications, were investigated. The nominal size of TiO₂ P25 nanoparticles is 21 nm, but they easily agglomerate in aqueous media, depending on pH and ionic strength. TiO₂ P25 aqueous dispersions were stabilized by alkanediyl-α,ω-bis-N-dodecyl-N, N′-dimethyl-ammonium bromide, cationic Gemini surfactant. The optimal conditions required to obtain stable dispersions, without formation of large agglomerates, were experienced. The stabilization of TiO₂ P25 nanoparticles by cationic Gemini surfactant was investigated in some details. Different amounts of Gemini surfactant were used, at concentrations between 1.0 and 250 × 10⁻⁶ mol L⁻¹, well below the critical micelle concentration. Dynamic light scattering and zeta potential analyses estimated the particle size and the dispersions stability. When the proper amount of Gemini surfactant was used, the resulting nanoparticles were still poly-disperse, but large agglomerates disappeared and were remarkably redispersible.     

Improvement of the dissolution rate of silymarin by means of solid dispersions

Solid dispersions of silymarin were prepared by the fusion method with the intention of improving the dissolution properties of silymarin. Polyethylene glycol 6000 (PEG 6000) was used as the inert hydrophilic matrix. The dissolution studies of the solid dispersions were performed in vitro. And the results obtained showed that the dissolution rate of silymarin was considerably improved when formulated in solid dispersions with PEG 6000 as compared to original drug, and the increased dissolution rate might be favorable for further oral absorption.     

Enhancement of dissolution rate of valdecoxib by solid dispersions technique with PVP K 30 & PEG 4000: preparation and in vitro evaluation

Solid dispersions of valdecoxib were prepared with the objective of dissolution enhancement by melt granulation technique using polyvinyl pyrollidone (PVP K 30) and polyethylene glycol (PEG 4000) alone (1:1) and in combination (1:0.5:0.5). Phase solubility studies showed a linear increase in valdecoxib solubility with increase in polymer concentration in both the cases. The FTIR spectroscopic studies showed the stability of valdecoxib and absence of well defined valdecoxib—PVP K 30–PEG 4000 interaction. Powder X-ray diffraction (XRD) and differential scanning calorimeter (DSC) were used to characterize the solid state of the dispersion, indicated a complete transformation of drug from crystalline to amorphous form. In vitro dissolution studies performed in 0.1 N HCl showed a significant enhance in dissolution rate when PEG 4000 and PVP K 30 were used in combination. Improved drug dissolution by both the carriers may be attributed to the improved wettability, reduction in drug crystallinity and solubilizing effects from solid dispersions of valdecoxib. Accelerated stability studies of solid dispersion with PVP K 30 and PEG 4000 does not show any significant change in the drug content and dissolution profile in 6 months study period. This study concluded that the dissolution rate of valdecoxib can be modulated by appropriate levels of hydrophilic carriers.     

Lactose as a low molecular weight carrier of solid dispersions for carbamazepine and ethenzamide

Solid dispersions of carbamazepine or ethenzamide were prepared by melting and rapid cooling with liquid nitrogen using lactose as a carrier. The physical characteristics of these solid dispersions were investigated by powder X-ray diffraction, differential scanning calorimetry, and dissolution rate analysis. The degree of crystallinity of the drugs in solid dispersions decreased with decreases in the molar ratio of the drugs to lactose. Fourier-transform infrared (FT-IR) analysis demonstrated the presence of intermolecular hydrogen bonds between the primary amide group of carbamazepine and lactose. Dissolution studies indicated that the dissolution rate was markedly increased in solid dispersions compared with physical mixtures and pure drugs. These results indicated that lactose is useful as a carrier for the production of solid dispersions of drugs having a primary amide group in their structures.     

Dissolution-enhancing mechanism of alkalizers in poloxamer-based solid dispersions and physical mixtures containing poorly water-soluble valsartan

The purpose of this study was to investigate the effects of alkalizers in dissolution rate and crystal structure of valsartan (VAL) in Poloxamer 407 (POX)-based solid dispersions (SD). VAL, a poorly-water soluble drug was selected as a model drug because of its low solubility at low pH. The POX-based SDs containing alkalizers (Na?CO?, MgO, meglumine and arginine) were prepared by melting method. The dissolution tests were performed using the United States Pharmacopeia (USP) paddle II method in enzyme-free simulated gastric fluid (pH 1.2) for 2 h. Microenvironmental pH (pH(M)) was examined potentiometrically by using a surface pH electrode. Dissolution rate of SD incorporating Na?CO? was drastically increased. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) data indicated that crystalline structure of VAL in SD was transformed to amorphous form by the addition of alkalizers but could not explain the differences in the dissolution rates. The molecular interaction between VAL and Na?CO? was observed in the Fourier transform infrared spectroscopy (FT-IR) spectra by the shift of C=O band from 1732 to 1719 cm?1 and the disappearance of carbonyl group at 1598 cm?1. Furthermore, Na?CO? efficiently modulated pH(M) by providing a favorable microenvironment for drug dissolution. A combination of SD method and use of alkalizer is a promising approach to modulate release rate of poorly water-soluble and ionizable drug with an aid of changes of drug crystallinity, molecular interaction and pH(M).     

Thermal stability of solid dispersions of naphthalene derivatives with β-cyclodextrin and β-cyclodextrin polymers

The thermal stabilities of some naphthalene derivatives (1-naphthyl acetate, 2-acetylnaphthalene, 1-naphthol) in β-cyclodextrin (β-CD) inclusion complexes and in β-CD-containing polymeric systems (Polyβ-CD) have been studied using thermal and thermogravimetric analyses and infrared spectroscopy. In β-CD systems, the stability of the 1-naphthyl acetate complex is lower than that of the 2-acetylnaphthalene complex, and both are more stable than the corresponding physical mixtures. For Polyβ-CD systems, the solid dispersions result much more stable than the corresponding β-CD ones, both at room temperature and at 60 °C. In the case of Polyβ-CD, besides the inclusion within CD cavities, the interaction of the guest with the crosslinking network confers an additional stability against volatilization. In contrast, an analogous crosslinked polymer prepared using sucrose instead of β-CD does not retain noticeable amounts of the naphthalene derivatives.     

Graphene dispersions

Aqueous dispersions of graphene are of interest to afford environmentally safe handing of graphene for coating, composite, and other material applications. The dispersion of graphene in water and some other solvents using surfactants, polymers, and other dispersants is reviewed and results show that nearly completely exfoliated graphene may be obtained at concentrations from 0.001 to 5% by weight in water. The molecular features promoting good dispersion are reviewed. A critical review of optical extinction shows that the visible absorption coefficients of graphene have been reported over the ranges of 12 to 66 cm²/mg at various wavelengths. The practice of energetically activating graphene in various solvents with various stabilizers followed by centrifugation to isolate the “good” dispersion components is fine for producing samples amenable to TEM analysis and quantification, but cannot be expected to drive value added production of products on the kg or higher scale. Such approaches lack practical application and often involve 90–99% wasted graphene. However, alternative approaches omitting centrifugation are yielding dispersions 0.5 to 5% by weight graphene, with higher yields likely in the near future. These dispersions yield effective extinctions of about 49 cm²/mg, in conformity with macroscopic optical analysis of single and few layer graphene.