Increased physical stability and improved dissolution properties of itraconazole, a class II drug, by solid dispersions that combine fast- and slow-dissolving polymers

Solid dispersions were prepared of itraconazole-Eudragit E100, itraconazole-PVPVA64, and itraconazole-Eudragit E100/PVPVA64 using a corotating twin-screw hot-stage extruder. Modulated temperature differential scanning calorimetry (MTDSC) was used to evaluate the miscibility of the extrudates, and dissolution experiments were performed in simulated gastric fluid without pepsin (SGF(sp)). Itraconazole and Eudragit E100 are miscible up to 13% w/w drug loading. From that concentration on, phase separation is observed. Pharmaceutical performance of this dispersion was satisfactory because 80% of the drug dissolved after 30 min. Extrudates of itraconazole and PVPVA64 were completely miscible but the pharmaceutical performance was low, with 45% of drug dissolved after 3 h. Combination of both polymers in different ratios, with a fixed drug loading of 40% w/w, was evaluated. MTDSC results clearly indicated a two-phase system consisting of itraconazole-Eudragit E100 and itraconazole-PVPVA64 phases. In these extrudates, no free crystalline or glassy clusters of itraconazole were observed; all itraconazole was mixed with one of both polymers. The pharmaceutical performance was tested in SGF(sp) for different polymer ratios, and Eudragit E100/PVPVA64 ratios of 50/50 and 60/40 showed significant increases in dissolution rate and level. Polymer ratios of 70/30 and 80/20, on the other hand, had a release of 85% after 30 min. Precipitation of the drug was never observed. The combination of the two polymers provides a solid dispersion with good dissolution properties and improved physical stability compared with the binary solid dispersions of itraconazole.     

The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

Surface-active derivative of inulin (Inutec® SP1) is a superior carrier for solid dispersions with a high drug load

The aim of this study was to compare the applicability of inulin, its surface-active derivative (Inutec? SP1), and polyvinylpyrrolidone (PVP) as carriers in high drug load solid dispersions (SDs) for improving the dissolution rate of a range of lipophilic drugs (diazepam, fenofibrate, ritonavir, and efavirenz). The SDs were prepared by spray freeze-drying. Scanning electron microscopy showed that the obtained samples were highly porous spherical particles. Modulated differential scanning calorimetry showed that the drugs incorporated in these carriers were fully or partially amorphous. The solubility of the drugs in solutions of the different carriers was increased in an order: inulin 2.3 kDa < PVP K30 ? Inutec? SP1. The dissolution behavior of SD tablets was evaluated. Inutec? SP1-based SD tablets showed the best performance followed by PVP- and inulin-based SD tablets. The superior dissolution behavior of the drugs from Inutec? SP1-based SDs could be ascribed to its surface-active nature. In addition, Inutec? SP1-based SD tablets gave good physical stability at 20 °C/45% relative humidity (RH) and 40 °C/75% RH for 3 months.     

Solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) hydrogels.

The applicability of cross-linked hydrogels in forming solid molecular dispersions to enhance the delivery of poorly soluble drugs has not been fully explored. The purpose of this study is to characterize physicochemical parameters affecting the formation of solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels and to investigate the effect of storage humidity levels on their physical stability. Samples were prepared by an equilibrium solvent loading process, using diclofenac sodium, piroxicam and naproxen as model drugs. These were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), as well as changes in the physical state during storage under different humidity conditions. The results show that a threshold drug loading level of about 30% exists in these solid molecular dispersions, above which amorphous to crystalline transition may occur. At any given drug loading, the onset of such change in physical state is accelerated at higher relative humidity levels during storage. The presence of hydrogen bonding between the polymer and the drug, as reflected in the observed FTIR band shifts, improves the compatibility between the drug and the polymer. This, together with a decreased mobility in the glassy polymer, helps to retard the crystallization event below the loading threshold. An increase in dissolution rate is also observed from the polymeric solid molecular dispersion as compared with that of the crystalline pure drug. These physicochemical results indicate that solid molecular dispersions based on PHEMA hydrogels can effectively enhance the dissolution and therefore should be potentially useful in improving the oral bioavailability of poorly water-soluble drugs.     

New binary solid dispersion of indomethacin with surfactant polymer: From physical characterization to in vitro dissolution enhancement

This article investigated preparation of solid dispersions containing a poor water-soluble drug, indomethacin (IND), and a new surfactant polymer, polyoxyethylene 32 distearate (POED). Solid dispersions were prepared by the melting method and characterized by DSC, hot-stage microscopy (HSM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). DSC and HSM analyses performed on IND/POED physical mixtures indicated that IND could dissolve in liquid POED. The materials showed complete miscibility at liquid state. Combination of DSC, XRD, and SEM revealed that these materials had limited miscibility at the solid state. Up to 20% w/w IND in POED, we did not detect significant modification of physical properties of the polymer. It supports the formation of a solid solution of IND in solid POED. Above 20% w/w, the solid dispersions presented particular behavior upon heating (recrystallization of IND) and at the solid state (presence of some IND crystallites). Under 3-month storage at 25°C/53% RH, the solid dispersions demonstrated a good stability of the samples. Finally, in vitro dissolution studies showed that IND release was greatly improved (5.5–12 times as fast) by formation of solid dispersion. This enhancement was principally attributed to the high dispersion of IND in POED and to the polymer surfactant properties. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1399–1413, 2010     

Clinical study of solid dispersions of itraconazole prepared by hot-stage extrusion.

The aim of this study was to investigate the performance of three new solid dispersion formulations of itraconazole in human volunteers in comparison with Sporanox, the marketed form. Solid dispersions made up of itraconazole (40%, w/w) and HPMC 2910, Eudragit E100 or a mixture of Eudragit E100-PVPVA64 were manufactured by hot-stage extrusion and filled in gelatin capsules. The formulations were tested in eight human volunteers in a double blind, single dose, and cross-over study. Concentrations of the drug and its metabolite hydroxyitraconazole in the plasma were determined using HPLC. The in vivo performance was evaluated by comparing the mean area under the plasma concentration-time curves (AUC), the mean maximum plasma concentration (C(max)), and the mean time to reach C(max) (T(max)). The mean bioavailability of itraconazole was comparable after administration of the HPMC solid dispersion, compared to Sporanox, while it was lower after administration of the Eudragit E100 or Eudragit E100-PVPVA64 dispersions. Due to high variability, a significant decrease in AUC and C(max) was only observed for the Eudragit E100-PVPVA formulation. Although the solid dispersions showed different in vitro dissolution behaviour, T(max) values were comparable. The same observations with respect to AUC, C(max) and T(max) could be made for hydroxyitraconazole. The present results indicate that hot-stage extrusion can be considered as a valuable alternative for manufacturing solid dispersions of itraconazole.     

Use of Surfactants as Plasticizers in Preparing Solid Dispersions of Poorly Soluble API: Stability Testing of Selected Solid Dispersions

Purpose The purpose of the study is to evaluate the effect of surfactant-plasticizers on the physical stability of amorphous drug in polymer matrices formed by hot melt extrusion.Method Solid dispersions of a poorly soluble drug were prepared using PVP-K30, Plasdone-S630, and HPMC-E5 as the polymeric carriers and surfactants as plasticizers. The solid dispersions were produced by hot melt extrusion at temperatures 10°C above and below the glass transition temperature (Tg) of the carrier polymers using a 16 mm-Haake Extruder. The surfactants tested in this study included Tween-80 and Docusate Sodium. The particle size of the extrudate was reduced to have mean of 100–200 micron. The physical stability of the solid dispersions produced was monitored at 30°C/60% for six-months and at 60°C/85% for two-months in open HDPE bottles. Modulated differential scanning calorimetry, polarized light microscopy, powder X-ray diffraction and dissolution testing was performed to assess the physical stability of solid dispersions upon stress testing.Results The dispersions containing HPMC-E5 were observed especially to be susceptible to physical instability under an accelerated stress conditions (60°C/85%RH) of the solid dispersion. About 6% conversion of amorphous drug to crystalline form was observed. Consequently, the system exhibits similar degree of re-crystallization upon addition of the surfactant. However, under 30°C/60%RH condition, the otherwise amorphous Drug-HPMC-E5 system has been destabilized by the addition of the surfactant. This effect is much more reduced in the extruded solid dispersions where polymeric carriers such as Plasdone S-603 and PVP-K30 (in addition to surfactants) are present. Furthermore, the drug release from the solid dispersions was unaffected at the stress conditions reported above.Conclusions Possible reasons for the enhanced stability of the dispersions are due to the surfactants ability to lower the viscosity of the melt, increase the API solubility and homogeneity in the carrier polymer. In contrast, while it is possible for the surfactants to destabilize the system by lowering the Tg and increasing the water uptake, the study confirms that this effect is minimal. By and large, the surfactants appear to be promising plasticizers to produce solid dispersions by hot melt extrusion, in so doing improving dissolution rate without compromising the physical stability of the systems.     

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability

To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 μg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C_max and T_max compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.     

Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion--Part I

Solid dispersions containing different ratios of itraconazole and hydroxypropylmethylcellulose (HPMC) were prepared by solvent casting. Based on dose, differential scanning calorimetry and dissolution results, a drug/polymer ratio of 40/60 w/w was selected in order to prepare dispersions by melt extrusion. The melt extrusion process was characterized using a design of experiments (DOE) approach. All parameter settings resulted in the formation of an amorphous solid dispersion whereby HPMC 2910 5 mPas prevents re-crystallization of the drug during cooling. Dissolution measurements demonstrated that a significantly increased dissolution rate was obtained with the amorphous solid dispersion compared to the physical mixture. The outcome of DOE further indicated that melt extrusion is very robust with regard to the itraconazole/HPMC melt extrudate characteristics. Stability studies demonstrated that the itraconazole/HPMC 40/60 w/w milled melt extrudate formulation is chemically and physically stable for periods in excess of 6 months as indicated by the absence of degradation products or re-crystallization of the drug.     

Enhancement of dissolution of cyclosporine A using solid dispersions with polyoxyethylene (40) stearate

A solid dispersion containing cyclosporine A (CyA) and polyoxyethylene (40) stearate (PS) was prepared by the solvent-melt method and characterized by powder X-ray diffraction (PXRD), hot-stage microscopy (HSM), scanning electron microscopy (SEM) and dissolution studies. The crystalline peaks of CyA disappeared in the PXRD spectra of solid dispersions but were seen in those of physical mixtures, demonstrating the amorphous state of the drug in solid dispersions. The solubility of CyA in aqueous solutions of PS was increased linearly with increasing amount of PS in water. Dissolution of the drug from solid dispersions and physical mixtures was dramatically enhanced compared to the drug powder alone in water at 37 degrees C.     

Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions

This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.     

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.     

Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion

The aim of the study was the formulation of solid dispersions of the poorly water-soluble drug celecoxib and a polymethacrylate carrier by hot-melt extrusion. The objectives were to elucidate the mechanism of drug release from obtained extrudates and milled strands addicted to the solid-state properties of the solid dispersions and to examine and eliminate stability problems occurring under storage, exposure of mechanical stress, and in vitro dissolution.Transparent extrudates containing up to 60% drug could be prepared with a temperature setting below the melting point of celecoxib. XRPD and DSC measurements indicated the formation of a glassy solid solution, where the drug is molecularly dispersed in the carrier. The amorphous state of the glassy solid solution could be maintained during the exposure of mechanical stress in a milling process, and was stable under storage for at least 6 months. Solid-state properties and SEM images of extrudates after dissolution indicated a carrier-controlled dissolution, whereby the drug is molecularly dispersed within the concentrated carrier layer. The glassy solid solution showed a 58-fold supersaturation in 0.1 N HCl within the first 10 min, which was followed by a recrystallization process. Recrystallization could be inhibited by an external addition of HPMC.     

Identification of Phase Separation in Solid Dispersions of Itraconazole and Eudragit® E100 Using Microthermal Analysis

Purpose. To evaluate the phase separation in itraconazole/Eudragit® E100 solid dispersions prepared by hot-stage extrusion. Methods. Extrudates were prepared using a corotating twin-screw extruder at 180°C. Micro-TA was used to evaluate the phase separation, where the AFM mode is used to visualize the different phases and local thermal analysis (LTA) to characterize the different phases Results. Itraconazole formed a homogeneous mixture with Eudragit® E100 with drug concentrations up to approximately 20%. Above this concentration, phase separation was observed. MTDSC revealed two T_gs and the mesophase of free glassy itraconazole. Performing micro-TA on the surface of these dispersions indicated an increase in sample roughness in the z-axis piezo signal, which could be an indication of free glassy itraconazole. However, thermal conductivity did not reveal differences between separate phases. Performing LTA, where only a small area (20 × 20 m) is heated, showed two separate and mixed phases of itraconazole and Eudragit® E100. Tip penetration in itraconazole and Eudragit® E100 occurred at 332K and 383K respectively. The difference in tip penetration was explained in terms of the difference in fragility. Conclusion. Micro-TA makes it possible to characterize separate phases of itraconazole and Eudragit® E100, thereby confirming the MTDSC results on phase separation.     

Physicochemical characterization of solid dispersions of three antiepileptic drugs prepared by solvent evaporation method

We have investigated the solid dispersion and dissolution profiles of three antiepileptic drugs (carbamazepine (CBZ), oxcarbazepine (OXC) and rufinamide (RFN)) with different aqueous solubilities, prepared by the solvent evaporation method. Solid dispersions of the three drugs in hydroxy-propylmethylcellulose (HPMC), with drug:polymer ratios of 1:4, were prepared and characterized by differential scanning calorimetry (DSC), Fourier transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy. The release mechanism was also investigated and the kinetic order of the solid dispersions was evaluated. It appeared that the dissolution behaviour depended on the physicochemical properties of the drug and drug-polymer interactions. DSC thermographs showed amorphous forms for all drugs confirmed by XRD patterns. The FTIR spectra of CBZ and OXC demonstrated drug interactions with HPMC through hydrogen polymer bonds. Thus, solid dispersions of these drugs had an improved dissolution profile. In contrast, solid dispersions of RUF showed modest enhancement of dissolution, suggesting negligible drug-polymer interactions. The different dissolution behaviour is attributed to the extent of interactions between the polymer hydroxyl group and the drug amide groups.     

Development of amorphous dispersions of artemether with hydrophilic polymers via spray drying: Physicochemical and in silico studies

Artemether (ARM) is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2, 1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) to identify the physicochemical interaction between drug and carrier, as well as effect on dissolution. The prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared to neat ARM, which was confirmed by DSC and XRD. Drug/polymer interactions were studied in-silico by docking and molecular dynamics which indicated formation of van der Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation SD3 showed highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and were stable over a period according to ICH guidelines. These findings suggest that an amorphous solid dispersion of ARM could be a viable option for enhancing the dissolution rate of ARM.     

Characterization of Solid Dispersions of Itraconazole and Hydroxypropylmethylcellulose Prepared by Melt Extrusion,Part II

Purpose. This study was done to elucidate the physical and pharmaceutical properties of itraconazole-HPMC dispersions and the influence of water on the phase separation. Methods. Extrudates were prepared using a corotating twin-screw hot-stage extruder with fixed process parameters. Modulated-temperature differential scanning calorimetry (MTDSC) and DSC 111 were used to examine the mixing behavior of itraconazole and the carrier by evaluation of the glass transition region. High temperature diffuse reflectance infrared transform spectroscopy (HT-DRIFT) was performed to reveal interactions between itraconazole and HPMC. Dissolution was performed to investigate the pharmaceutical performance of the dispersions. Results. Although the dissolution rate of itraconazole significantly increased, we found that the solid dispersions do not form a homogeneous system. A different picture was obtained depending on the way MTDSC analysis was performed, i.e., using open or closed sample pans. Water can evaporate in open pans, which allows itraconazole to interact with HPMC and leads to a partially mixed phase. Analysis in hermetically closed pans revealed a further phase separation as water remains on the sample and impedes the interaction between drug and polymer. Conclusions. Solid dispersions of itraconazole and HPMC do not form a homogeneous phase.     

热熔挤出技术制备伊曲康唑固体分散体及体外溶出考察

以羟丙甲纤维素(HPMC E5)为分散载体,利用热熔挤出技术制备难溶性药物伊曲康唑固体分散体,并探究不同挤出工艺参数和增塑剂1,2-丙二醇(PG)含量对固体分散体溶出度的影响。结果表明,二次挤出制得的固体分散体中药物的溶出率大于直接挤出的固体分散体,且二者均明显大于物理混合物。使用PG作增塑剂后伊曲康唑固体分散体的溶出率得到了显著提高,当PG用量较高(10%)时,固体分散体在0.1 mol/L盐酸介质中的溶出率可达到93%。本研究可以为热熔挤出的工艺开发提供更多的思路,同时为进一步制备高规格(200 mg)伊曲康唑片剂提供帮助。     

Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process

Solid dispersions of felodipine were formulated with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. The mean particle size of the solid dispersions was 200-250 nm; these had a relatively regular spherical shape with a narrow size distribution. The particle size of the solid dispersions from the CSE method increased at 1 h after dispersed in distilled water. However, the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data. The equilibrium solubility of the felodipine solid dispersion prepared by the SAS process was 1.5-20 microg/ml, while the maximum solubility was 35-110 microg/ml. Moreover, the solubility of felodipine increased with decreasing drug/polymer ratio or increasing HCO-60 content. The solid dispersions from the SAS process showed a high dissolution rate of over 90% within 2 h. The SAS process system may be used to enhance solubility or to produce oral dosage forms with high dissolution rate.     

热熔挤出法增加布洛芬的溶出度并掩盖其苦味

目的:制备布洛芬固体分散体,以增加布洛芬的溶出度并掩盖其苦味。方法:取布洛芬原料药与丙烯酸树脂Eudragit EPO,以1∶1.5(w/w)混合,采用热熔挤出法制备布洛芬固体分散体。用差示扫描量热法和粉末X射线衍射法分析布洛芬在Eudragit EPO中的分散状态。测定固体分散体、物理混合物和市售布洛芬片剂的溶出度,并评价布洛芬固体分散体的掩味效果。结果:布洛芬晶体结构的特征峰在差示扫描量热和粉末X射线衍射图中消失。在磷酸盐缓冲液中,固体分散体的溶出速度大于物理混合物和布洛芬片。志愿者对布洛芬固体分散体的味觉评价优于物理混合物和布洛芬原料。结论:热熔挤出法制备的Eudragit EPO固体分散体能增加布洛芬的溶出度,并有明显的掩味效果。