Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

Cryoprotection mechanisms of polyethylene glycols on lactate dehydrogenase during freeze-thawing

The purpose of this study was to explore the cryoprotection mechanisms of high molecular weight polyethylene glycols (PEGs) (eg, PEG 4000 and PEG 8000) on lactate dehydrogenase (LDH). Ultraviolet activity assays, circular dichroism (CD) spectroscopy, gel filtration, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), (14)C-PEG 4000 labeling and binding, and cryostage microscopic study were conducted. Different molecular weights and concentrations of PEGs in LDH formulations were treated by freeze-thawing. Higher molecular weights and concentrations of PEGs in LDH-PEG formulations obtained better activity and secondary structure recoveries of LDH after freeze-thawing. Insoluble aggregation of LDH was not observed in gel filtration studies. SDS-PAGE results suggested surface characteristic modifications of LDH by the larger molecular weight PEGs. The 14C-PEG 4000 labeling and binding study showed extensive nonspecific interactions between the PEG 4000 and LDH molecules in a concentration-dependent manner. The bound LDH-PEG 4000/free PEG 4000 ratio increased when LDH or PEG 4000 concentrations increased. Cryostage microscopic study showed that PEG 8000 delayed the ice crystallization and eutectic transition of LDH formulation. It appeared that multiple mechanisms were at work during PEGs' cryoprotection of LDH. It was unclear whether the delayed eutectic characteristics of PEGs contributed to LDH cryoprotection. The favorable interaction, rather than preferential exclusion, between LDH and PEGs (eg, 4000) cryoprotected LDH.     

Synthesis of poly(ethylene glycol)-metaxalone conjugates and study of its controlled release in vitro

Metaxalone (Met), a drug for treatment of pain and stiffness due to muscular injuries, was covalently linked to poly(ethylene glycols) (PEG) via a chloroacetyl chloride spacer. The average weight molecular weights used for PEG are 4000, 6000 and 10,000, respectively, and the procedure of chemical modification for PEGs was conducted by a two-step protocol: (1) synthesis of N-chloroacetyl-metaxalone; (2) synthesis of PEG(4000)-Met, PEG(6000)-Met and PEG(10000)-Met. The controlled drug release studies were performed in buffer solutions with pH values equal to 1.1, 7.4 and 10.0. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG(10000)-Met is the slowest among three prodrugs, and more amount of metaxalone can be detected releasing from prodrug matrices at the presence of alpha-chymotrypsin in a buffer solution with pH 8.0. It was also found that these novel prodrugs can effectively improve the metaxalone's pharmacokinetics, and furthermore can markedly increase its half-life period.     

呱西替柳滴丸的制备及其溶出度研究

采用差示扫描量热法、扫描电子显微镜术和溶出试验研究了呱西替柳-聚乙二醇(GA-PEG)低共熔混合物及其滴丸。结果表明,随着 PEG 分子量增高,低共熔混合物中药物的比例增加,但低共熔温度与PEG 分子量之间并无规律性。其中 GA-PEG4000的滴丸有较大的溶出度,加入崩解剂有助于增加滴丸与溶出介质接触的表面积,进而提高溶出度。     

Production of insulin-loaded poly(ethylene glycol)/poly(l-lactide) (PEG/PLA) nanoparticles by gas antisolvent techniques.

Insulin and insulin/poly(ethylene glycol) (PEG)-loaded poly(l-lactide) (PLA) nanoparticles were produced by gas antisolvent (GAS) CO(2) precipitation starting from homogeneous polymer/protein organic solvent solutions. Different amounts of PEG 6000 (0, 10, 30, 50, 100, and 200% PEG/PLA w/w) or concentration of 30% PEG/PLA with PEGs with different molecular weight (MW; 350, 750, 1900, 6000, 10,000, and 20,000) were used in the preparations. The process resulted in high product yield, extensive organic solvent elimination, and maintenance of > 80% of the insulin hypoglycemic activity. Nanospheres with smooth surface and compact internal structure were observed by scanning electron microscopy. The nanospheres presented a mean particle diameter in the range 400-600 nm and narrow distribution profiles. More than 90% of drug and PEG were trapped in the PLA nanoparticles when low MW PEGs were used in the formulation, whereas the addition of high MW PEGs significantly reduced the loading yield. In all cases, in vitro release studies showed that only a little amount of drug was released from the preparations. However, formulations containing low MW PEGs allowed for a slow but constant drug release throughout 1500 h, whereas a burst was obtained by increasing the PEG MW. In conclusion, the GAS process offers a mean to produce protein-loaded nanoparticles possessing the prerequisites for pharmaceutical applications. The PEG added to the formulation was found to play a key role in the simultaneous solute precipitation phenomena and in determining the release behavior and the chemical-physical properties of the formulation.     

Impact of molecular weight on the mechanism of cellular uptake of polyethylene glycols (PEGs) with particular reference to P-glycoprotein

Polyethylene glycols (PEGs) in general use are polydisperse molecules with molecular weight (MW) distributed around an average value applied in their designation e.g., PEG 4000. Previous research has shown that PEGs can act as P-glycoprotein (P-gp) inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs. However, questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed. In this study, we examined the mechanism of uptake of PEGs by MDCK-mock cells, in particular, the effect of MW and interaction with P-gp by MDCK-hMDR1 and A549 cells. The results show that: (a) the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors; (b) PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil; and (c) uptake of PEGs of low MW (<2000 Da) occurs by passive diffusion whereas uptake of PEGs of high MW (>5000 Da) occurs by a combination of passive diffusion and caveolae-mediated endocytosis. These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.     

Characterization and stability of solid dispersions based on PEG/polymer blends

Solid dispersions were prepared by a melting method from the water-insoluble model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500) or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in order to combine advantages of the different carrier polymers (recrystallization inhibition, processability and stability). The solid dispersions were characterized by dissolution, powder X-ray diffractometry and microscopy directly after preparation and after storage for 3 and 6 months at 25 °C/0% relative humidity (RH) or 3 months at 40 °C/75% RH. More than 80% drugs were released from all solid dispersions within 20 min. The dissolution rate of carbamazepine decreased in the order of PEG 1500 > PEG 1500/Eudragit > PEG 1500/PVP 30 > PEG 1500/PVPVA > PEG 1500/PVP 12. The dissolution rank order was not directly correlated to the amorphous/crystalline state of the drugs, but rather to the properties of the PEG 1500/polymer compositions. Nifedipine was released in the order of PEG 1500 > PEG 1500/PVPVA > PEG 1500/PVP 30 > PEG 1500/PVP 12 > PEG 1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer dispersions except in pure PEG 1500 solid dispersion. The significant increase in dissolution rate of PEG 1500 solid dispersions was due to the reduced crystallinity of the drug and the excellent solubilisation properties of PEG 1500. After 6 months storage at 25 °C/0% RH, the solid dispersions released both drugs in the order PEG 1500/PVPVA > PEG 1500/PVP 30 > PEG 1500/PVP 12 > PEG 1500/Eudragit > PEG 1500. The stabilized amorphous state of the drug resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or PEG 1500/PVP stored for 3 months at 40 °C/75% RH showed phase separation due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15-hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the dissolution rate and the physical state of the drug was significant.     

The mechanochemical preparation of solid disperse systems of ibuprofen-polyethylene glycol

The method of mechanical activation is applied to obtain a solid-state dispersion of ibuprofen in polyethylene glycol (PEG). The release rate and solubility of the drug was found to depend on carrier molecular weight and its weight fraction. The highest release rate and solubility were achieved in systems containing equimolar amounts of the drug and PEG 4000 or PEG 6000. It was shown by IR-spectroscopy and fluorescence measurements that the mechanical treatment gives rise to an interaction between ibuprofen and PEG that was a cause of the effects observed.     

Mechanism of increased dissolution of diazepam and temazepam from polyethylene glycol 6000 solid dispersions

Solid dispersion literature, describing the mechanism of dissolution of drug-polyethylene glycol dispersions, still shows some gaps; (A). only few studies include experiments evaluating solid solution formation and the particle size of the drug in the dispersion particles, two factors that can have a profound effect on the dissolution. (B). Solid dispersion preparation involves a recrystallisation process (which is known to be highly sensitive to the recrystallisation conditions) of polyethylene glycol and possibly also of the drug. Therefore, it is of extreme importance that all experiments are performed on dispersion aliquots, which can be believed to be physico-chemical identical. This is not always the case. (C). Polyethylene glycol 6000 (PEG6000) crystallises forming lamellae with chains either fully extended or folded once or twice depending on the crystallisation conditions. Recently, a high resolution differential scanning calorimetry (DSC)-method, capable of evaluating qualitatively and quantitatively the polymorphic behaviour of PEG6000, has been reported. Unraveling the relationship between the polymorphic behavior of PEG6000 in a solid dispersion and the dissolution characteristics of that dispersion, is a real gain to our knowledge of solid dispersions, since this has never been thoroughly investigated. The aim of the present study was to fill up the three above mentioned gaps in solid dispersion literature. Therefore, physical mixtures and solid dispersions were prepared and in order to unravel the relationship between their physico-chemical properties and dissolution characteristics, pure drugs (diazepam, temazepam), polymer (PEG6000), solid dispersions and physical mixtures were characterised by DSC, X-ray powder diffraction (Guinier and Bragg-Brentano method), FT-IR spectroscopy, dissolution and solubility experiments and the particle size of the drug in the dispersion particles was estimated using a newly developed method. Addition of PEG6000 improves the dissolution rate of both drugs. Mechanisms involved are solubilisation and improved wetting of the drug in the polyethylene glycol rich micro-environment formed at the surface of drug crystals after dissolution of the polymer. Formulation of solid dispersions did not further improve the dissolution rate compared with physical mixtures. X-ray spectra show that both drugs are in a highly crystalline state in the solid dispersions, while no significant changes in the lattice spacings of PEG6000 indicate the absence of solid solution formation. IR spectra show the absence of a hydrogen bonding interaction between the benzodiazepines and PEG6000. Furthermore, it was concluded that the reduction of the mean drug particle size by preparing solid dispersions with PEG6000 is limited and that the influence of the polymorphic behavior of PEG6000 (as observed by DSC) on the dissolution was negligible.     

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.     

联苯双酯的共沉淀物和固体分散物的制备及其对湿度的稳定性

联苯双酯从它的PVP共沉淀物和它的PEG4000、PEG6000的固体分散物中的体外溶出速率明显高于市售片剂(P<0.01),非离子表面活性剂对联苯双酯的共沉淀物和固体分散物体外溶出速率几乎无影响,联苯双酯的固体分散物对湿度(75%RH,40℃)的稳定性高于其共沉淀物。     

Influence of polyethylene glycol chain length on compatibility and release characteristics of ternary solid dispersions of itraconazole in polyethylene glycol/hydroxypropylmethylcellulose 2910 E5 blends

The present study aims to elucidate the influence of the polyethylene glycol chain length on the miscibility of PEG/HPMC 2910 E5 polymer blends, the influence of polymer compatibility on the degree of molecular dispersion of itraconazole, and in vitro dissolution. PEG 2000, 6000, 10,000 and 20,000 were included in the study. Solid dispersions were prepared by spray drying and characterized with MDSC, XRPD and in vitro dissolution testing. The polymer miscibility increased with decreasing chain length due to a decrease in the Gibbs free energy of mixing. Recrystallization of itraconazole occurred as soon as a critical temperature of ca. 75 degrees C was reached for the glass transition that represents the ternary amorphous phase. Due to the lower miscibility degree between the longer PEG types and HPMC 2910 E5, the ternary amorphous phase was further separated, leading to a more rapid decrease of the ternary amorphous phase glass transition as a function of PEG and itraconazole weight percentage and hence, itraconazole recrystallization. In terms of release, an advantage of the shorter chain length PEG types (2000, 6000) over the longer chain length PEG types (10,000, 20,000) was observed for the polymer blends with 5% of PEG with respect to the binary itraconazole/HPMC 2910 E5 solid dispersion. Among the formulations with a 15/85 (w/w) PEG/HPMC 2910 E5 ratio on the other hand, there was no difference in the release profile.     

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     

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。     

Absorption of Polyethylene Glycols 600 Through 2000: The Molecular Weight Dependence of Gastrointestinal and Nasal Absorption

Polyethylene glycols (PEGs) 600,1000, and 2000 were used to study the molecular weight permeability dependence in the rat nasal and gastrointestinal mucosa. Absorption of the PEGs was measured by following their urinary excretion over a 6-hr collection period. HPLC methods were used to separate and quantitate the individual oligomeric species present in the PEG samples. The permeabilities of both the gastrointestinal and the nasal mucosae exhibited similar molecular weight dependencies. The steepest absorption dependence for both mucosae occurs with the oligomers of PEG 600, where the extent of absorption decreases from approximately 60% to near 30% over a molecular weight range of less than 300 daltons. Differences in the absorption characteristics between the two sites appear in the molecular weight range spanned by PEG 1000. For these oligomers, the mean absorption from the nasal cavity is approximately 14%, while that from the gastrointestinal tract is only 9%. For PEG 2000, mean absorption decreases to 4% following intranasal application and below 2% following gastrointestinal administration. Within the PEG 1000 and 2000 samples, however, very little molecular weight dependency is seen among the oligomers. In the range studied, a distinct molecular weight cutoff was not apparent at either site.     

Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories

Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000) with high molecular weight (4000 and 6000) in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.     

Effects of polyethylene glycol molecular weight and concentration on lactate dehydrogenase activity in solution and after freeze-thawing

Lactate dehydrogenase (LDH) is a tetrameric enzyme that has been used as a model for labile protein drugs. Polyethylene glycols (PEGs) have been proposed as excipients to stabilize labile proteins in solution and during the freezing portion of the lyophilization cycle. The aim of this study was to determine the effects of PEG molecular weight and concentration on the activity of LDH. In general, PEG protection increases with PEG molecular weight and concentration. PEGs slow the loss of activity in LDH solutions stored at 4 degrees C, but are not sufficiently effective to allow for a solution product. PEGs 8000, 10,000, and 20,000 show full freezing protection at less than 0.01%, while lower molecular weight PEGs need higher concentrations to produce protection upon freezing. Circular dichroism (CD) studies of LDH solutions before and after freezing with PEG 400 and PEG 8000 confirm the activity studies. The CD spectrum of LDH before freezing shows the classic alpha helix pattern. After unprotected LDH solution is frozen and thawed, the CD spectrum erodes. Low concentrations of PEG 8000 (1% or less) preserve the alpha helix profile after freezing of the samples. PEG 400 preserves the alpha helix CD profile in a stepwise fashion with increasing concentrations. The CD and activity data suggest that PEGs can protect alpha helix structures and activity of LDH through the freezing process.     

The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites.

Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Büchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.     

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.     

Solubility of selected derivatives of 1,4-benzodiazepin-2-one in solid dispersions in PEG 6000

Pharmaceutical availability of diazepam, oxazepam and nitrazepam from solid dispersions of PEG 6000 have been studied in comparison with corresponding physical mixtures and pure benzodiazepines. Selected derivatives of 1,4-benzodiazepin-2-one are poorly water soluble drugs. The aim of this work was to report the properties of diazepam- and nitrazepam-PEG 6000 solid dispersions. Differential scanning calorimetry (DSC) and X-ray diffraction were used to characterize the solid dispersions. The effect of PEG 6000 on the dissolution of selected derivatives of 1,4-benzodiazepin-2-one was investigated. The dissolution of diazepam, oxazepam and nitrazepam from its solid dispersions increased in the presence of PEG 6000.