Characteristics of Rofecoxib-Polyethylene Glycol 4000 Solid Dispersions and Tablets Based on Solid Dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion–based rofecoxib tablets by the direct compression method. Solid dispersion–based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion–based oral tablets.     

In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000

OBJECTIVE: Gliclazide is a potent antidiabetic agent because of its capability to decrease blood glucose level via stimulating endogenous insulin secretion from beta-pancreas cells. Gliclazide is insoluble in water and has low dissolution rate. In this study, polyethylene glycol (PEG) 6000 was used as a matrix to disperse gliclazide in the solid state, and the pharmacokinetic profile of this solid dispersion was studied in rats. DESIGN: The solid dispersion of Gliclazide:PEG 6000 (1:4) was prepared by solvent evaporation method. MAIN OUTCOME MEASURES: Samples characterization included differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and solubility and dissolution test. In vivo study was carried out in healthy rats, randomly. After a single dose of oral administration, blood samples were collected pre-dose (15 min before) and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post-dose. Plasma concentration of gliclazide was determined by high pressure liquid chromatography method using C-18 column, with mobile phase KH2PO4 (pH 4.6)-acetonitril (40:60 v/v) and UV detection at 229 nm. RESULTS: Results showed that there were no differences in DSC, IR spectroscopy, XRD, and dissolution test between the solid dispersion and physical mixture. In vivo data showed that the Tmax of gliclazide in solid dispersion and physical mixture was significantly decreased, while the Cmax, AUC(0-12), and AUC(0-infinity) were significantly increased compared to gliclazide alone. These results indicate that the rapid Tmax was due to rapid absorption of gliclazid across the GI tract membrane. Increased Cmax, AUC(0-12), and AUC(0-infinity) indicate a better absorption of gliclazide in solid dispersion and physical mixture than of gliclazide alone. CONCLUSION: Increased in gliclazide dissolution in the presence of PEG 6000 was followed by improved in vivo data.     

Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion-based rofecoxib tablets by the direct compression method. Solid dispersion-based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion-based oral tablets.     

Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), and evaluated for solubility, in-vitro drug release and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FT-IR spectra showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low temperature melting method using polyethylene glycol 4000 (PEG 4000) as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and absorption rate of ibuprofen.     

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 of Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

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.     

Solid dispersion of meloxicam: factorially designed dosage form for geriatric population

The objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethyl cellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23 factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.     

替硝唑固体分散体的制备及其体外释放特性研究

目的:利用固体分散技术制备替硝唑固体分散体,增加替硝唑溶解度和溶出速度。方法:以聚乙二醇(PEG)为载体材料,采用溶剂-熔融法制成固体分散体,测定表观溶解度,进行体外溶出试验,并采用差示扫描量热(DSC)法鉴别药物在固体分散体中的存在状态。结果:替硝唑的溶出度和表观溶解度随PEG的比例不同而不同,且溶出度随载体用量增加而增加。固体分散体的DSC曲线中替硝唑药物的特征熔融峰消失。结论:所制得的固体分散体能明显提高替硝唑的溶出度和表观溶解度。     

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.     

A calorimetric investigation into the interaction between paracetamol and polyethlene glycol 4000 in physical mixes and solid dispersions.

The solubility, heat of solution and dissolution rate of paracetamol and polyethyelene glycol 4000 (PEG 4000) systems have been studied in order to clarify the nature of the interaction between the two components during dissolution of solid dispersions. The logarithmic solubility of paracetamol demonstrated a non-linear increase with concentration of PEG 4000, while linear relationships between heat of solution in water and concentration were seen for both individual components. However, the heat of solution of paracetamol was found to decrease with increasing concentrations of PEG 4000. Similarly, the heats of solution in water of physical mixes and solid dispersions prepared using two manufacturing protocols were found to be lower than the theoretical values calculated from those corresponding to the individual components. Drug release studies showed a marked increase in paracetamol dissolution rate when prepared as a solid dispersion, with behaviour consistent with carrier controlled dissolution observed at low drug contents which was ascribed to enhanced dissolution of the drug into the diffusion layer of the PEG 4000. The implications of the understanding of this mechanism for the choice of carrier and manufacturing protocol for solid dispersion products is discussed.     

非诺贝特固体分散片的试制

以PEG4000和十二烷基硫酸钠为载体，采用溶剂—熔融法制备了非诺贝特固体分散体，再与适当辅料混合压片制得非诺贝特固体分散片。用正交设计表L9(3^4)筛选处方。溶出度实验表明自制片较市售两种制剂溶出快。     

Improvement of the dissolution kinetics of SR 33557 by means of solid dispersions containing PEG 6000

Solid dispersions of SR 33557 in preparations containing from 30 to 80% w/w polyethylene glycol 6000 (PEG 6000) were prepared by the fusion method. The solubility of the drug substance either alone or in solid dispersions was determined in pH 1.2 and 4.5 media (extraction fluid NFXII, without enzyme). A large increase in the solubility was noted from the 80% w/w PEG preparation. A wettability study performed by measuring the contact angle on tablets of either drug substance or PEG 6000, or solid dispersions, revealed a minimal contact angle for the 80% w/w PEG 6000 solid dispersion (eutectic composition of SR 33557/PEG 6000 phase diagram). Dissolution kinetic analysis performed at pH 1.2 on all solid dispersions, on the physical mixtures containing 70 and 80% w/w PEG 6000, and on SR 33557 alone, showed a maximum release rate (100%) for the solid dispersions containing 70 and 80% w/w PEG 6000. The dissolution rate of the physical mixtures was faster than that of the drug substance alone but remained, however, lower than that of the solid dispersions, at the same composition. It was also observed that the dissolution rate, at pH 1.2 and 4.5, of the 70% w/w PEG 6000 solid dispersion was practically pH independent, which was not the case for the drug substance alone. The latter solid dispersion showed a slowing down of the dissolution kinetics after 3 months storage at 50°C whereas no change in the dissolution rate was observed following storage for 12 months at 25°C.     

Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000.

Solid dispersions and physical mixtures of Zolpidem in polyethylene glycol 4000 (PEG 4000) and 6000 (PEG 6000) were prepared with the aim to increase its aqueous solubility. These PEG based formulations of the drug were characterized in solid state by FT-IR spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. By these physical determinations no drug-polymer interactions were evidenced. Both solubility and dissolution rate of the drug in these formulations were increased. Each individual dissolution profile of PEG based formulation fitted Baker-Lonsdale and first order kinetic models. Finally, significant differences in ataxic induction time were observed between Zolpidem orally administered as suspension of drug alone and as solid dispersion or physical mixture. These formulations, indeed, showed almost two- to three-fold longer ataxic induction times suggesting that, in the presence of PEG, the intestinal membrane permeability is probably the rate-limiting factor of the absorption process. Copyright     

微管蛋白抑制剂SUD-35固体分散体的制备、鉴定及初步体外药效学研究

目的将难溶性微管蛋白抑制剂SUD-35制备成固体分散体,以增加其溶解度及溶出速率。方法以聚乙二醇6000为载体,溶剂-熔融法制备SUD-35固体分散体。采用差示扫描量热分析与X-射线衍射观察药物在载体中的存在状态,并进行溶解度和体外溶出度研究。采用MTT法对SUD-35固体分散体对小鼠白血病L1210细胞药效进行测定。结果 SUD-35固体分散体中SUD-35的溶解度和溶出速率相对原料药和物理混合物均有明显提高,差示扫描量热分析与X-射线衍射结果显示SUD-35以无定型状态存在于固体分散体中,细胞药效结果显示SUD-35固体分散体对小鼠白血病L1210细胞增殖抑制率强于SUD-35纯药。结论聚乙二醇6000为载体制备SUD-35固体分散体,可显著提高SUD-35的溶解度及溶出速率。     

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。     

Enhanced release of solid dispersions of etodolac in polyethylene glycol

This work examines the release of etodolac from various molecular weight fractions of polyethylene glycol (PEG) solid dispersions. Solid dispersions of etodolac were prepared in different molar ratios of drug/carrier by using solvent and melting methods. The release rate of etodolac from the resulting complexes was determined from dissolution studies by use of USP dissolution apparatus 2 (paddle method). The physical state and drug:PEG interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The dissolution rate of etodolac is increased in all of the solid dispersion systems compared to that of the pure drug and physical mixtures. The solid dispersion compound prepared in the molar ratio of 1:5 by the solvent method was found to have the fastest dissolution profile. The physical properties did not change after 9 months storage in normal conditions.     

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000

The aim of this study was to prepare and characterize solid dispersions of water insoluble non-steroidal anti-inflammatory drug, indomethacin (IND), with polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) for enhancing the dissolution rate of the drug. The solid dispersions (SDs) were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy (SEM), X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND–Gelu. and disappeared in case of higher ratio of IND–PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer (1:4) enhanced the drug solubility about 4-folds or 3.5-folds in case of SDs of IND–PEG or IND–Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures (PMs) or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer.     

Structural properties of polyethylene glycol-polysorbate 80 mixture, a solid dispersion vehicle.

The structural properties of the mixtures of polysorbate 80 with various polyethylene glycols (PEG), viz., PEG 1000, PEG 1450, PEG 3350, and PEG 8000, have been investigated by powder X-ray diffraction (XRD) and differential scanning calorimetric studies. These mixtures may be used as solid dispersion vehicles to insure complete dissolution of poorly water-soluble drugs. Although polysorbate 80 is a liquid at room temperature, the PEG-polysorbate 80 mixtures with up to 75% (w/w) polysorbate 80 were solid. The XRD studies revealed that the crystal structures (d-spacings) of the PEGs (M(r) 1000, 1450, 3350, and 8000) did not change with increasing amounts of polysorbate 80 in the mixture. The intensities of the XRD peaks, however, varied approximately in proportion to the concentration of PEG present. Similarly, the differential scanning calorimetric studies showed that the melting behavior of a PEG-polysorbate 80 mixture was similar to that of the PEG used. The lowering of the mp of a particular PEG due to the presence of 50% (w/w) polysorbate 80 in the mixture was < 6 degrees C, and the decrease in mp was < 12 degrees C in the presence of 75% (w/w) polysorbate 80. When enthalpies of fusion of the mixtures were normalized for the amounts of PEGs present, they were similar to those of pure PEGs. These results indicate that the crystalline structure of PEG in a PEG-polysorbate 80 mixture is substantially the same as that of the pure PEG, and that polysorbate 80 is incorporated into the amorphous region of PEG solid structure.     

Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions

The solid state behaviour of polyethylene glycol 4000 (PEG 4000) and dispersions of a homologous series of parabens (methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- (BP)) were examined and compared to the paraben solubility in liquid PEG 400. Dispersions were prepared by co-melting different amounts of paraben (5–80% (w/w)) and PEG 4000 and were studied using a combination of differential scanning calorimetry (DSC) and small and wide angle X-ray diffraction (SAXD/WAXD). Depending on the concentration of parabens in the dispersions, DSC showed melting peaks from folded and unfolded forms of PEG, a eutectic melting and melting of pure parabens. The fraction of folded PEG increased and the melting temperatures of both PEG forms decreased with increasing paraben content. In an apparent phase diagram of PP–PEG dispersions a eutectic mixture appeared above 5% PP. In addition, a melting peak corresponding to the paraben appeared for dispersion containing more than 60% PP. Similar phase diagrams were shown for the other parabens. The SAXD data and a 1D correlation function analysis revealed that MP and BP were incorporated into the amorphous domains of the lamellae of solid PEG to a higher degree than EP and PP. In addition, the lamellae thickness of PEG and the fraction of amorphous domains increased more for MP and BP compared to EP and PP. BP showed the highest solubility of the parabens followed by MP, EP and PP in both liquid and solid PEG. Furthermore, the thickness of the amorphous domains of the PEG in the different parabens–PEG dispersions could be correlated to the solubility in liquid PEG 400.     

硝苯地平固体分散体制备工艺的研究

目的利用固体分散技术将硝苯地平制成固体分散体,提高其体外溶出速率。方法分别以聚乙二醇6000(PEG6000)、聚乙二醇4000(PEG4000)、聚乙烯吡咯烷酮K30(PVPK30)、泊洛沙姆188(Pluronic F68)等为载体,用熔融法、溶剂法、溶剂-熔融法和喷雾干燥法制备硝苯地平固体分散体。采用差热分析法(DTA)分析药物在固体分散体中的存在状态,并进行体外溶出度试验。结果各种固体分散体均能加快药物的溶出速率,并且随着载体在固体分散体中的比例增大,溶出速率增大。DTA分析显示硝苯地平在PVPK30的固体分散体中以微细结晶存在。结论将硝苯地平制成固体分散体能显著提高硝苯地平的体外溶出速率。