Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug. Copyright     

A comparison of spray drying and milling in the production of amorphous dispersions of sulfathiazole/polyvinylpyrrolidone and sulfadimidine/polyvinylpyrrolidone

Formulations containing amorphous active pharmaceutical ingredients (APIs) present great potential to overcome problems of limited bioavailability of poorly soluble APIs. In this paper, we directly compare for the first time spray drying and milling as methods to produce amorphous dispersions for two binary systems (poorly soluble API)/excipient: sulfathiazole (STZ)/polyvinylpyrrolidone (PVP) and sulfadimidine (SDM)/PVP. The coprocessed mixtures were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and intrinsic dissolution tests. PXRD and DSC confirmed that homogeneous glassy solutions (mixture with a single glass transition) of STZ/PVP were obtained for 0.05 ≤ X(PVP) (PVP weight fraction) < 1 by spray drying and for 0.6 ≤ X(PVP) < 1 by milling (at 400 rpm), and homogeneous glassy solutions of SDM/PVP were obtained for 0 < X(PVP) < 1 by spray drying and for 0.7 ≤ X(PVP) < 1 by milling. For these amorphous composites, the value of T(g) for a particular API/PVP ratio did not depend on the processing technique used. Variation of T(g) versus concentration of PVP was monotonic for all the systems and matched values predicted by the Gordon-Taylor equation indicating that there are no strong interactions between the drugs and PVP. The fact that amorphous SDM can be obtained on spray drying but not amorphous STZ could not be anticipated from the thermodynamic driving force of crystallization, but may be due to the lower molecular mobility of amorphous SDM compared to amorphous STZ. The solubility of the crystalline APIs in PVP was determined and the activities of the two APIs were fitted to the Flory-Huggins model. Comparable values of the Flory-Huggins interaction parameter (χ) were determined for the two systems (χ = -1.8 for SDM, χ = -1.5 for STZ) indicating that the two APIs have similar miscibility with PVP. Zones of stability and instability of the amorphous dispersions as a function of composition and temperature were obtained from the Flory-Huggins theory and the Gordon-Taylor equation and were found to be comparable for the two APIs. Intrinsic dissolution studies in aqueous media revealed that dissolution rates increased in the following order: physical mix of unprocessed materials < physical mix of processed material < coprocessed materials. This last result showed that production of amorphous dispersions by co-milling can significantly enhance the dissolution of poorly soluble drugs to a similar magnitude as co-spray dried systems.     

Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique.

Solid dispersions (SDs) of glibenclamide (GBM); a poorly water-soluble drug and polyglycolized glycerides (Gelucire with the aid of silicon dioxide (Aerosil 200); as an adsorbent, were prepared by spray drying technique. SDs and spray dried GBM in comparison with pure GBM and corresponding physical mixtures (PMs) were initially characterized and then subjected to ageing study up to 3 months. Initial characterization of SDs and spray dried GBM by DSC and XRPD showed that GBM was present in its amorphous form (AGBM). Improvement in the solubility and dissolution rate was observed for all samples. DRIFT spectroscopy revealed presence of hydrogen bonding in SDs. During ageing study, almost no decrease of in vitro drug dissolution was observed, over the period of 3 months as compare with freshly prepared SDs. Slight crystallinity in SDs was observed in the DSC and XRPD studies during ageing. Moreover in vivo study in Swiss Albino mice also justified the improvement in the therapeutic efficacy of amorphous GBM in SDs over pure GBM. Thus, present study demonstrated the high potential of spray drying technique for obtaining stable free flowing SDs of poorly water-soluble drugs using polyglycolized glycerides carriers with the aid of silicon dioxide as an adsorbent.     

Enhanced dissolution rate of celecoxib using PVP and/or HPMC-based solid dispersions prepared by spray drying method

Celecoxib with low solubility and high permeability (BCS class II) in water is a non-steroidal anti-inflammatory drug used in the treatment of pain and inflammation, associated with rheumatoid arthritis, and several other inflammatory disorders. Also, it is a selective cyclooxygenase 2 inhibitor with low water solubility and high crystallinity. The objective of this study was to improve dissolution rate of celecoxib which was water-insoluble drug. Solid dispersions were prepared by spray drying as the solvent evaporation method. The dissolution behavior of solid dispersions was compared with Celebrex^® (Pfizer) as a control group in simulated gastric juice (pH 1.2, 0.5 % SLS. The characterization of the prepared solid dispersions is analyzed by scanning electron microscope, powder X-ray diffractometer, Fourier transform infrared spectroscopy and reverse phase-high performance liquid chromatography The best formulation was SD 8 in this study. It was the cumulative release of 97 % at 120 min. This study suggests that the solubility and bioavailability of poorly water-soluble celecoxib improved through the prepared solid dispersions by spray drying method.     

Preparation, characterization and in vitro dissolution of aceclofenac-loaded PVP solid dispersions prepared by spray drying or rotary evaporation method

This study was conducted to enhance dissolution rate of aceclofenac (ACF) with extremely low solubility and high permeability (BCS class II) in water using poly vinyl pyrrolidone (PVP) and sodium lauryl sulfate as carriers. Solid dispersions were prepared by spray drying method and rotary evaporation method using different ratios of ACF and polymers. The characterization of solid dispersions was evaluated by scanning electron microscopy, Fourier transformation infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometer. The dissolution behavior of solid dispersions was compared with pure ACF (API) and Airtal^® (Deawoong, Co, Korea) as control groups in simulated phosphate buffer at pH 6.8. The dissolution rate of the drug was affected by nature and amount of polymer used. The prepared solid dispersion of ACF/PVP (1:5) appeared to have the highest dissolution rate. Therefore, solid dispersion techniques of spray drying and rotary evaporation method can be successfully used for the enhancement of the dissolution rate of ACF.     

Physicochemical characterization and dissolution study of solid dispersions of Lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to-carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

螺旋霉素超细粉的喷干法和反溶剂法制备及性质研究

摘要：目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可 以很好地解决这些问题; 方法 采用了两种代表性的方法制备螺旋霉素的超细粉：分别为喷雾干燥法和反溶剂法;并以粒径为 指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种 方法的最佳条件为：喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均 粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均 粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪 (DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干 燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于 制药业,为微粉技术提供技术思路。     

螺旋霉素超细粉的喷干法和反溶剂法制备及性质研究

目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可以很好地解决这些问题;方法 采用了两种代表性的方法制备螺旋霉素的超细粉：分别为喷雾干燥法和反溶剂法;并以粒径为指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种方法的最佳条件为：喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪(DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于制药业,为微粉技术提供技术...     

Characterization and solubility study of solid dispersions of flunarizine and polyvinylpyrrolidone

Flunarizine is a selective calcium entry blocker poorly water-soluble. In this report, the interactions of this drug with polyvinylpyrrolidone in solid dispersions, prepared according to the dissolution method using methanol as the solvent, have been investigated. For purposes of comparison physical mixtures were prepared by simple mixture and homogeneization of the two pulverized components. Combinations of flunarizine/polyvinylpyrrolidone of the following percentage proportions were prepared: 10/90, 20/80, 30/70, 40/60, 50/50, 60/40 and 80/20 (mean particle size of 0.175 mm). The physicochemical properties of solid dispersions were investigated with X-ray diffraction, infrared spectroscopy, differential scanning calorimetry and solubility in equilibrium. X-ray patterns and differential scanning calorimetry have shown that polyvinylpyrrolidone inhibits the crystallization of flunarizine when percentages drug/polymer are 10/90, 20/80 and 30/70. The infrared spectra suggest that there was no chemical interaction between flunarizine and polyvinylpyrrolidone. Equilibrium solubility studies showed that drug solubility was enhanced as the polymer content increased. In general, the solubility increase was greater in solid dispersions than in physical mixtures and the solubility in equilibrium for solid dispersions and physical mixtures at the same drug/polymer proportion showed significant differences (P < 0.05).     

Anomalous properties of spray dried solid dispersions

The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83°C (acetone/water) to 103°C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724–4737, 2009     

Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Spray drying is an efficient technology for solid dispersion manufacturing since it allows extreme rapid solvent evaporation leading to fast transformation of an API-carrier solution to solid API-carrier particles. Solvent evaporation kinetics certainly contribute to formation of amorphous solid dispersions, but also other factors like the interplay between the API, carrier and solvent, the solution state of the API, formulation parameters (e.g. feed concentration or solvent type) and process parameters (e.g. drying gas flow rate or solution spray rate) will influence the final physical structure of the obtained solid dispersion particles. This review presents an overview of the interplay between manufacturing process, formulation parameters, physical structure, and performance of the solid dispersions with respect to stability and drug release characteristics.     

Dissolution and precipitation behavior of amorphous solid dispersions

Amorphous solid dispersions (ASDs) are widely utilized in the pharmaceutical industry for bioavailability enhancement of low solubility drugs. The important factors governing the dissolution behavior of these systems are still far from adequately understood. As a consequence, it is of interest to investigate the behavior of these systems during the dissolution process. The purpose of this research was twofold. First, the degree of supersaturation generated upon dissolution as a function of drug-polymer composition was investigated. Second, an investigation was conducted to correlate physical behavior upon dissolution with polymer loading. Felodipine and indomethacin were selected as model drugs and hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were used to form the dispersions. Diffusion and nuclear magnetic resonance spectroscopy experiments revealed that the extent of bulk supersaturation generated on dissolution of the ASD did not depend on the drug-polymer ratio. Interestingly, the maximum supersaturation generated was similar to the predicted amorphous solubility advantage. However, dynamic light scattering measurements revealed that particles on the submicron scale were generated during dissolution of the solid dispersions containing 90% polymer, whereas solid dispersions at a 50% polymer loading did not yield these nanoparticles. The nanoparticles were found to result in anomalous concentration measurements when using in situ ultraviolet spectroscopy. The supersaturation generated upon dissolution of the solid dispersions was maintained for biologically relevant timeframes for the HPMC dispersions, whereas PVP appeared to be a less effective crystallization inhibitor.     

Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25.

The glass forming properties of ketoconazole were investigated using differential scanning calorimetry (DSC), by quench cooling liquid ketoconazole from T(m)+10 to 273.1 K, followed by subsequent heating at 5 K/min to T(m)+10 K. It was shown that liquid ketoconazole forms a glass which did not recrystallise following reheating, indicating its stability; T(g) was found to be 317.5+/-0.3 K. However, the presence of a small amount of crystalline ketoconazole was able to convert the amorphous drug back to the crystalline state: the addition of only 4.1% (w/w) of crystalline material converted 77.1% of the glass back to the crystalline state, and this value increased as the amount of added crystals increased. PVP K25 was found to be highly effective in the prevention of such recrystallisation, but only if the amorphous drug was formulated in a solid dispersion, since physical mixing of amorphous ketoconazole with the polymer resulted in recrystallisation of the former compound. Storage of the solid dispersions for 30 days at 298.1 K (both 0 and 52% RH) in the presence or absence of crystals did not result in recrystallisation of the amorphous drug. Solid dispersions formed compatible blends as one single T(g) was observed, which gradually increased with increasing amounts of PVP K25, indicating the anti-plasticising property of the polymer. The values of T(g) followed the Gordon-Taylor equation, indicating no significant deviation from ideality and suggesting the absence of strong and specific drug-polymer interactions, which was further confirmed with 13C NMR and FT-IR. It can be concluded therefore that the physical mechanism of the protective effect is not caused by drug-polymer interactions but due to the polymer anti-plasticising effect, thereby increasing the viscosity of the binary system and decreasing the diffusion of drug molecules necessary to form a lattice.     

超临界抗溶剂技术制备对乙酰氨基酚-PEG4000固体分散体

以水难溶药物对乙酰氨基酚为模型体系，研究了超临界二氧化碳抗溶剂法(PCA和GAS)制备乙酰氨基酚-PEG分散体微细颗粒的影响因素，用电子扫描显微镜、X射线衍射仪和示差扫描量热仪研究了颗粒的物理性质，发现经PCA和GAS处理后，颗粒分散性增强，与水的接触面积增大，溶出速度和溶出量均随之增大。研究表明．超临界抗溶剂过程是制备固体分散体的一个可行的方法。     

Solid-state characterization of nifedipine solid dispersions

The purpose of this study is to characterize the nature and solid-state properties of a solid dispersion system of nifedipine (33.3% w/w) in a polymer matrix consisting of Pluronic F68 (33.3% w/w) and Gelucire 50/13 (33.3% w/w). The nature of nifedipine dispersed in the matrix was studied by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The rate and extent of water uptake of the solid dispersion were determined by weight gain. The dissolution rate of nifedipine solid dispersion was determined using Apparatus 2 of USP XXIII (1995). Quantitative PXRD showed that the saturation solubility of nifedipine in the polymer matrix is 2.1-3.0% w/w and indicated an excess of crystalline nifedipine in the solid dispersion. The maximum water uptake by the solid dispersion exposed to 75% RH at 45 degrees C was 3.3 times higher than for the dispersion exposed to 65% RH at 25 degrees C. Over 8 weeks, PXRD and DRIFTS of the nifedipine matrix stored at 25 or 4 degrees C were unchanged, showing constancy of crystallinity and intermolecular interactions. For a given mass of nifedipine (20 mg) and for a given particle size of nifedipine (<850 microm), the initial release rate of nifedipine from the solid dispersion was faster (46.2% of the nifedipine dissolved in 20 min) than that of the pure drug (1.2% of the nifedipine dissolved in 20 min). The results indicate that the nifedipine solid dispersion is physically stable over 8 weeks. Nifedipine is released faster from the solid dispersion than from the pure crystalline drug of the same particle size.     

Study of the physicochemical properties and stability of solid dispersions of loperamide and PEG6000 prepared by spray drying.

Solid dispersions of PEG6000 and loperamide-a poorly water-soluble agent-were prepared by spray drying. Their physicochemical properties were evaluated immediately after preparation. The dissolution was higher than that of pure crystalline loperamide. DSC- and XRD-measurements revealed that in the dispersions, loperamide is partially present in the crystalline state. A eutectic state diagram was obtained. The samples containing 20% loperamide were stored under different conditions (40 degrees C and 0% RH, 25 degrees C and 52% RH, 4 degrees C and 0% RH) to investigate their stability as a function of time. The dissolution properties deteriorate upon storage at high temperature (40 degrees C and 0% RH) and in conditions of higher relative humidity (25 degrees C and 52% RH). The DSC-curves clearly indicate an increase in the amount of crystalline compound under these conditions. From these observations it could be concluded that loperamide, which is partially crystalline and partially amorphous in the freshly prepared samples, continues to crystallize under these conditions, resulting in progressively poorer dissolution properties.     

Preparation and characterization of metoprolol controlled-release solid dispersions

In recent years, great attention has been paid to using solid dispersions to make sustained-release drugs. The objective of this study is to produce sustained-release systems of metoprolol tartrate using solid dispersion techniques and to evaluate their physicochemical characteristics. The solid dispersions were produced by melting and solvent methods, containing 7%, 15%, or 25% of the drug and different ratios of Eudragit RLPO and RSPO in ratios of 0:10, 3:7, 5:5, 7:3, and 10:0. Drug release profiles were determined by USP XXIII rotating paddle method in phosphate buffer solution (pH 6.8). XRD, DSC, IR, and microscopic observations were performed to evaluate the physical characteristics of solid dispersions. Results showed that the drug release from dispersions was at a slower rate than pure drug and physical mixtures. Moreover, the formulations containing greater ratios of Eudragit RSPO showed slower release rates and smaller DE_8% but larger mean dissolution time than those containing greater ratios of Eudragit RLPO. Dispersions with particle size of less than 100 μm containing 7% of metoprolol and Eudragit RL:RS 5:5 (solvent method) and those with the ratio of 3:7 (melting method) had similar release pattern to Lopressor® sustained-release tablets by zero-order and Higuchi kinetics, respectively.     

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.     

Preparation and characterization of solid dispersions of Quercetin with PEG4000

Objective To enhance the solubility,quicken the speed of digesting and absorption,and increase the bioavailability of quercetin(3,3',4',5,7-pentahydroxyflavone).Methods A series of Quercetin-PEG4000 solid dispersions were prepared by fusion method.The configuration and property of solid dispersion were characterized by solubility tests,dissolution tests,FTIR spectra,differential scanning calorimetry(DSC)and microphotograph.Results 1.According to solubility tests the the mass ratio of quercetin to PEG4000 affected strongly on the solubility of solid dispersions,on the whole,the relation of the solubility of solid dispersions to the mass ratio presented linear relationship.The preparation temperature had little effect on the solubility of solid dispersions.The surface-active agent,polysorbate80 increased strongly the solubility of solid dispersions.2.According to the dissolution tests,the mass ratio of quercetin to PEG4000 affected strongly on the dissolution of solid dispersions,the preparation temperature had little effect on the dissolution of solid dispersions.The surface-active agent,polysorbate80 increased strongly the dissolution of solid dispersions,and after addition polysorbate80,the dissolution of solid dispersions was two times of the dissolution of solid dispersions without polysorbate80.3.According to the DSC results,except that a little of quercetin molecular existed as crystalline state in the solid dispersion with the mass ratio was qu:PEG=1:2,quercetin existed as amorphous phase in other mass ratio solid dispersion.4.According to the FTIR spectra and microphotograph results,the relation of quercetin and PEG4000 was mainly physical mixing in quercetin-PEG4000 solid dispersion.Quercetin was just like solute in solution,and PEG4000 was just like solvent in solution.The force between quercetin and PEG4000 was mainly hydrogen bonding,so the biological activity of quercetin would not be influenced greatly after the formation solid dispersion.Conclusions These results suggest that quercetin existed mainly as amorphous phase in solid dispersion;the solubility and the dissolution in water were increased obviously after formation the solid dispersion.     

Characterization of curcumin-PVP solid dispersion obtained by spray drying

Curcumin, a naturally occurring highly lipophilic molecule has wide range of pharmacological activities. However, its limited aqueous solubility and degradation at alkaline pH restricts its bioavailability. Solid dispersions of curcumin in different ratios with PVP were prepared by spray drying. Physical characterization by SEM, IR, DSC, and XRPD studies, in comparison with corresponding physical mixtures revealed the changes in solid state during the formation of dispersion and justified the formation of high-energy amorphous phase. Dissolution studies of curcumin and its physical mixtures in 0.1 N HCl showed negligible release even after 90 min. Whereas, solid dispersions showed complete dissolution within 30 min. This may aid in improving bioavailability and dose reduction of the drug.