In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells

In this study improvement in the bioavailability of carbamazepine (CBZ) prepared as solid dispersions by conventional solvent evaporation and supercritical fluid (SCF) processing methods was assessed, along with the elucidation of the mechanism of improved absorption. Solid dispersions of CBZ in polyethylene glycol (PEG) with either Gelucire 44/14 or vitamin E-TPGS (TPGS) were evaluated by intrinsic dissolution. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of TPGS. Cell viability in presence of various concentrations of amphiphilic carriers was seen. In vivo oral bioavailability was determined in rats. The apparent intrinsic dissolution rates (IDR) of both conventional- and SCF-CBZ/PEG 8000/TPGS solid dispersions were increased by 13- and 10.6-fold, respectively, relative to neat CBZ. CBZ was not a substrate of P-glycoprotein. Higher CBZ permeability was seen in presence of 0.1% TPGS. Cell viability studies showed significant cytotoxicity only at or above 0.1% amphiphilic carrier. Supercritical treated formulation (without amphiphilic carrier) displayed oral bioavailability on par with those conventional solid dispersions augmented with amphiphilic carriers. An in vitro-in vivo correlation was seen between IDR and the AUC of the various CBZ solid dispersions. Bioavailability of CBZ was more a function of dissolution as opposed to membrane effects. Although bioavailability from SCF processed dispersions was better than conventionally processed counterparts (except for one formulation containing Gelucire 44/14), an interaction of processing method and inclusion of an amphiphilic carrier, rather by one factor alone contributed to optimal absorption, thus giving contradictory results for Gelucire 44/14 and TPGS formulations.     

In vitro Dissolution Studies on Solid Dispersions of Mefenamic Acid

Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid.     

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.     

Chemical Structural Effects of Amphipathic and Water-soluble Phospholipid Polymers on Formulation of Solid Dispersions

For the polymeric carriers of solid dispersions, it is important that carriers themselves dissolve quickly and maintain the supersaturated state of amorphous drugs during their dissolution period to improve bioavailability. Amphipathic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers can be dissolved in water, owing to the extremely high hydrophilicity of the MPC units, and are used as an ideal feeder for drug molecules to form aggregates in aqueous conditions. We synthesized amphipathic MPC copolymers with different hydrophobic side chains and molar ratios of MPC units, and evaluated the effect of the polymers on dissolution rate and supersaturation maintenance of solid dispersions of indomethacin. In most of the water-soluble amphipathic MPC copolymers, “spring-parachute”-like dissolution behavior was observed, where the drug initially became supersaturated followed by slow precipitation. In particular, MPC copolymers with aromatic rings in their side chains or polymers with a high percentage of hydrophobic units remained in a supersaturated state for a longer period. In contrast, urethane groups, which form hydrogen bonds with drug molecules, could also interact with water and were not conducive to maintaining supersaturation. In addition, water solubility of the polymer is important for rapid dissolution.     

Enhancement of solubility and permeability of Candesartan cilexetil by using different pharmaceutical interventions

The poor solubility and wettability of Candesartan cilexetil (CAN) leads to poor dissolution and hence, low bioavailability after oral administration. The aim of the present study was to improve the solubility and dissolution rate and hence the permeability of CAN by preparing solid dispersions/inclusion complexes. Solid dispersions were prepared using PEG 6000 [hydrophilic polymer] and Gelucire 50/13 [amphiphilic surfactant] by melt agglomeration (MA) and solvent evaporation (SE) methods in different drug-to-carrier ratios, while inclusion complexes were made with hydroxypropyl-β-cyclodextrin (HP-β-CD) [complexing agent] by grinding and spray drying method. Saturation solubility method was used to evaluate the effect of various carriers on aqueous solubility of CAN. Based on the saturation solubility data, two drug-carrier combinations, PEG 6000 (MA 1:5) and HP-β-CD (1:1 M grinding) were selected as optimized formulations. FTIR, DSC, and XRD studies indicated no interaction of the drug with the carriers and provided valuable insight on the possible reasons for enhanced solubility. Dissolution studies showed an increase in drug dissolution of about 22 fold over the pure drug for PEG 6000 (MA 1:5) and 12 fold for HP-β-CD (1:1 M grinding). Ex-vivo permeability studies revealed that the formulation having the greatest dissolution also had the best absorption through the chick ileum. Capsules containing solid dispersion/ complex exhibited better dissolution profile than the marketed product. Thus, the solid dispersion/inclusion complexation technique can be successfully used for enhancement of solubility and permeability of CAN.     

Dissolution behaviour of nalidixic acid solid dispersions using water soluble dispersion carriers

The oral bioavailability of nalidixic acid (NA) is low due to its poor solubility and slow dissolution. Solid dispersions of NA containing varying concentrations of polyvinylpyrrolidone (PVP), beta-cyclodextrin (BCD) and sodium starch glycolate (SSG) were prepared by solvent evaporation technique in an attempt to improve dissolution rate of NA. Physical characterization of NA, physical mixtures (PM) and solid dispersions were investigated by a variety of analytical methods including scanning electron microscopy (SEM), infrared (IR) spectroscopy and powder X-ray diffraction (XRD). SEM was useful in the verification of possible nalidixic acid inclusion in the dispersion system by studying its surface and shape characteristics of different samples. IR analysis demonstrated no strong interaction between the drug and the carrier exists in the solid dispersions. The degree of crystallinity of nalidixic acid decreased and also differed with the dispersion systems of different carriers. Disolution studies indicated that the dissolution rate and percent dissolution efficiency (DE) were significantly increased in the solid dispersions compared with drug alone. The relative potency of the carriers to enhance the dissolution rate of nalidixic acid was in the order: BCD > PVP > SSG. The dissolution rate of the drug in the solid dispersions was faster when the ration of the drug to carrier was smaller. F-test suggests that first order model may be used for explaining the kinetics of drug release from all the solid dispersion systems.     

Effect of excipients on dissolution enhancement of aceclofenac solid dispersions studied using response surface methodology: a technical note

The aim of present study was to enhance the dissolution rate of poorly water-soluble drug aceclofenac by solid dispersion technique using corn starch, dicalcium phosphate, lactose, and microcrystalline cellulose as carriers. Solid dispersions were prepared by solvent wetting method using 3² full factorial design for each of the carrier. The prepared solid dispersions were evaluated for differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and angle of repose. In vitro dissolution studies were carried out in phosphate buffer (pH 7.5) and 0.1 N HCl (pH 1.2). The results of solid state characterization bring to view that in solid dispersions the crystalline drug gets converted to its amorphous form. FTIR study results indicated the absence of interaction between aceclofenac and carriers. For prepared solid dispersions, angle of repose was found to be in the range of 26.19° to 35.29°, which indicates good flowability. Enhanced drug dissolution was obtained with carrier in order lactose > corn starch > microcrystalline cellulose > dicalcium phosphate. Hence, these carriers could be used to enhance the dissolution rate of poorly water-soluble drug.     

布格呋喃固体分散体的体外研究

布格呋喃(buagafuran,AF-5)是以( )香芹酮为起始原料通过立体选择性合成的沉香呋喃类化合物[1].它具有显著的抗焦虑作用,毒副作用低,市场前景广阔.布格呋喃为油状液体,脂溶性强,不溶于水.用植物油稀释进行小鼠灌胃,抗焦虑活性与空白组比较无统计学意义,不能较好地发挥药效.室温放置易发生降解,化学稳定性差.这些缺     

The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers

Abstract

The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.     

Dissolution enhancement of felodipine by amorphous nanodispersions using an amphiphilic polymer: insight into the role of drug–polymer interactions on drug dissolution

Context: Felodipine, a poorly soluble drug, is widely used in the treatment of angina pectoris and hypertension.

Objective: This study aimed at the preparation of amorphous solid dispersion (SD) of felodipine using an amphiphilic polymer, soluplus, for the potential enhancement in solubility of the drug.

Materials and methods: Solid dispersions with varying proportions of drug and soluplus were prepared and the rate and extent of dissolution from SDs was compared with that of the pure drug. FT-IR and ¹H NMR spectroscopic analysis were carried out to examine the formation mechanism of SDs. Various techniques were used for solid state characterization of designed SDs.

Results: Formation of amorphous solid dispersions with particle size in nanometer range indicated suitability of polymer and method used in the preparation. FT-IR and ¹H NMR spectroscopy revealed that soluplus was involved in strong hydrogen bonding with felodipine molecules which resulted in the conversion of crystalline felodipine into amorphous form. Solid dispersion with 1:10 drug/polymer ratio showed more than 90% drug dissolution in 30?min whereas pure felodipine showed less than 19% drug dissolution in 1?h.

Discussion and conclusion: Amorphous SDs of felodipine were prepared using soluplus resulting in substantial enhancement in the rate and extent of dissolution of felodipine.     

Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons

The solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30) were evaluated and compared in an effort to improve aqueous solubility and bioavailability of a model hydrophobic drug. All preparations were characterized by differential scanning calorimetry, powder X-ray diffraction, intrinsic dissolution rates, and contact angle measurements. Accelerated stability studies also were conducted to determine the effects of aging on the stability of various formulations. The selected solid dispersion and solid solution formulations were further evaluated in beagle dogs for in vivo testing. Solid dispersions were characterized to show that the drug retains its crystallinity and forms a two-phase system. Solid solutions were characterized to be an amorphous monophasic system with transition of crystalline drug to amorphous state. The evaluation of the intrinsic dissolution rates of various preparations indicated that the solid solutions have higher initial dissolution rates compared with solid dispersions. However, after storage at accelerated conditions, the dissolution rates of solid solutions were lower due to partial reversion to crystalline form. The drug in solid dispersion showed better bioavailability in comparison to solid solution. Therefore, considering physical stability and in vivo study results, the solid dispersion was the most suitable choice to improve dissolution rates and hence the bioavailability of the poorly water soluble drug.     

浙贝提取物固体分散体的制备及溶出特性研究

目的：制备浙贝提取物固体分散体,考察其中贝母素甲及贝母素乙的溶出效果,从而确定制备的最佳方法和最佳比例。方法：选择聚乙二醇6000（PEG6000）与聚乙烯吡咯烷酮（PVP K30）两种载体材料,分别采用熔融法和溶剂法制备浙贝提取物固体分散体;通过比较提取物、固体分散体的溶出性能,确定最佳工艺。结果：使用HPLC-ELSD法测定贝母素甲及贝母素乙的溶出量,结果准确、可靠、稳定。制备成固体分散体能显著提高贝母素甲及贝母素乙的体外溶出速度;PEG6000作为载体的浙贝提取物固体分散体溶出速度快于PVP K30为载体的浙贝提取物固体分散体。结论：以PEG6000为载体,采用熔融法制备的药物/载体比例为1∶6的固体分散体能显著提高浙贝提取物中贝母素甲及贝母素乙的溶出速率。     

The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers

Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API. However, there are inconsistent dissolution performances of solid dispersion reported which entails further investigation. In this study, solid dispersions of ketoprofen in three hydrophilic carriers, i.e. PVP K30, PVPVA 6:4 and PVA were prepared and characterized. Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API. This result is coinciding to evaluation of drug–polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug–polymer interaction. XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA. Interestingly, dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system. Thus, it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.     

Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8?kDa, 4?kDa and 6.5?kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug.     

尼莫地平固体分散物的研究

尼莫地平临床上主要用于防治缺血性脑血管疾病．该药为难溶性药物，生物利用度低，本文采用了固体分散技术制备了尼莫地平两种固体分散物，其体外溶出速率１０分钟以内达８０％以上，较市售片有显著提高．两种固体分散物中，固体分散物Ⅰ为本实验室研制，固体分散物Ⅱ参照国内、外文献用ＰＶＰ为载体制备．两种固体分散物均能明显提高尼莫地平的体外溶出速率，但固体分散物Ⅱ易于老化，经相对湿度ＲＨ７５％４０℃贮藏３个月溶出速率明显下降，同样条件下，固体分散物Ⅰ则无明显变化．二种固体分散物Ｘ－射线衍射图谱表明尼莫地平以非晶体状态存在，而在ＲＨ７５％４０℃条件下放置３个月后，固体分散物ⅡＸ－射线衍射图谱出现了尼莫地平结晶峰．     

In sight into tadalafil - block copolymer binary solid dispersion: Mechanistic investigation of dissolution enhancement

Tadalafil is a phosphodiesterase-5 inhibitor that is characterized by low solubility and high permeability. Solid dispersion approach represents a promising carrier system for effective enhancement of dissolution and oral bioavailability of poorly soluble drugs. In the present work, novel tadalafil-loaded solid dispersions employing various block copolymers (Pluronics(?)) were prepared through fusion technique. Their solubility and dissolution properties were compared to the drug alone. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Furthermore, contact angle measurements were carried out. The sign and magnitude of the thermodynamic parameters indicated spontaneity of solubilization process. The phase solubility studies revealed A(L) type of curves for the carriers. Unlike traditional solid dispersion systems, the crystal form of drug in the formulated systems could not be converted to amorphous form. Most of the studied grades showed dissolution improvement vis-à-vis pure drug, with Pluronic F-127 as the most promising carrier. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model. Thus, the results demonstrated that tadalafil/Pluronic F-127 solid dispersion system is a direct and feasible technology which represents a potential candidate for delivering a poorly water-soluble drug with enhanced solubility and dissolution.     

Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods

This study compares the physicochemical properties of carbamazepine (CBZ) solid dispersions prepared by either a conventional solvent evaporation versus a supercritical fluid process. Solid dispersions of carbamazepine in polyvinylpyrrolidone (PVP) K30 with either Gelucire 44/14 or Vitamin E TPGS, NF (d-alpha-tocopheryl polyethylene glycol 1000 succinate) were prepared and characterized by intrinsic dissolution, differential scanning calorimetry, powder X-ray diffraction and Fourier transform infrared spectroscopy. CBZ/PVP K30 and CBZ/PVP K30/TPGS solid dispersions showed increased dissolution rate. The best intrinsic dissolution rate (IDR) was obtained for supercritically processed CBZ/PVP K30 that was four-fold higher than pure CBZ. Thermograms of various solid dispersions did not show the melting peak of CBZ, indicating that CBZ was in amorphous form inside the carrier system. This was further confirmed by X-ray diffraction studies. Infrared spectroscopic studies showed interaction between CBZ and PVP K30 in solid dispersions. The amorphous state of CBZ coupled with presence of interaction between drug and PVP K30 suggests fewer, if any, stability problems. Because the supercritical-based process produced solid dispersions with IDR better than conventional solid dispersions augmented with amphiphilic carriers, stability issues associated with lipid carriers do not apply, which, in turn, implies easier scale up under current Good Manufacturing Practice for this technique.     

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.     

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.