Physical stability of solid dispersions of the antiviral agent UC-781 with PEG 6000, Gelucire 44/14 and PVP K30

This paper describes the physical stability of solid dispersions of UC-781 with PEG 6000, Gelucire 44/14 and PVP K30 prepared by the solvent and melting methods. The concentration of the drug in the solid dispersions ranged from 5 to 80% w/w. The solid dispersions were stored at 4-8 and 25 degrees C (25% RH), then their physicochemical properties were analysed by differential scanning calorimetry (DSC), X-ray powder diffraction and dissolution studies as a function of storage time. The DSC curves of solid dispersions of UC-781 with PVP K30 did not show any melting peaks corresponding to UC-781 after storage, indicating no recrystallization of the drug. The DSC data obtained from PEG 6000 and Gelucire 44/14 showed some variations in melting peak temperatures and enthalpy of fusion of the carriers. It was shown that the enthalpy of fusion of PEG 6000 in the dispersions increased after storage; it was more pronounced for samples stored at 25 degrees C compared to those at 4-8 degrees C indicating the reorganization of the crystalline domains of the polymer. Similarly, the enthalpy of fusion of Gelucire 44/14 in the solid dispersions increased as a function of time. Dissolution of UC-781 from all solid dispersions decreased as a function of storage time. While these observations concurred with the DSC data for all solid dispersions, they were not reflected by X-ray powder diffraction data. It was concluded that it is the change of the physical state of the carriers and not that of the drug, which is responsible for the decreased dissolution properties of the solid dispersions investigated.     

Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14

The purpose of this study was to prepare and characterize solid dispersions of the antiviral thiocarboxanilide UC-781 with PEG 6000 and Gelucire 44/14 with the intention of improving its dissolution properties. The solid dispersions were prepared by the fusion method. Evaluation of the properties of the dispersions was performed using dissolution studies, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffraction. To investigate the possible formation of solid solutions of the drug in the carriers, the lattice spacings [d] of PEG 6000 and Gelucire 44/14 were determined in different concentrations of UC-781. The results obtained showed that the rate of dissolution of UC-781 was considerably improved when formulated in solid dispersions with PEG 6000 and Gelucire 44/14 as compared to pure UC-781. From the phase diagrams of PEG 6000 and Gelucire 44/14 it could be noted that up to approximately 25% w/w of the drug was dissolved in the liquid phase in the case of PEG 6000 and Gelucire 44/14. The data from the X-ray diffraction showed that the drug was still detectable in the solid state below a concentration of 5% w/w in the presence of PEG 6000 and Gelucire 44/14, while no significant changes in the lattice spacings of PEG 6000 or Gelucire 44/14 were observed. Therefore, the possibility of UC-781 to form solid solutions with the carriers under investigation was ruled out. The results from infrared spectroscopy together with those from X-ray diffraction and differential scanning calorimetry showed the absence of well-defined drug–polymer interactions.     

Enhancement of Solubility and Dissolution Rate of Loratadine with Gelucire 50/13

The objective of the current investigation was to enhance the solubility and dissolution rate of loratadine using solid dispersions (SDs) with Gelucire 50/13. SDs of loratadine using Gelucire 50/13 as carrier were prepared by the solvent evaporation method, characterized for drug content, dissolution behavior, and physicochemical characteristics by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) studies. At 10 % concentration of Gelucire 50/13, the increase in solubility was around 100-fold compared with pure drug. The solubility of loratadine in the presence of Gelucire 50/13 in water showed linear increase with increasing concentrations of Gelucire indicating A_L-type solubility diagrams. The mean dissolution time (MDT) of loratadine decreased after preparation of SDs with Gelucire 50/13 indicating increased dissolution rate. FTIR studies showed the stability of loratadine and the absence of a well-defined interaction. DSC and XRD studies revealed the amorphous state of loratadine in SDs which was further confirmed from SEM. From the dissolution parameters, it is evident that the solubility and dissolution rate of loratadine was enhanced by SDs with Gelucire 50/13.     

Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier

Solid dispersions of saquinavir mesylate containing either Gelucire^® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at ?20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire^® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95 % relative humidity and 40 °C/75 % (f ₂ values >50), respectively.     

Formulation of highly purified fenugreek gum based silica lipid drug delivery system for simvastatin with enhanced dissolution rate and in vitro characterization

In current study, highly purified fenugreek gum (HPFG) isolated by patented method explored as emulsifier and hydrophilic solid carrier in drug delivery system. Anti-hyperlipidemic drug simvastatin (SIM) was selected as drug model for the study as it is associated with poorly water solubility and low bioavailability problems (<5 %). A suitable HPFG-based silica lipid system composed of SIM (1.5 %), medium chain triglyceride Capmul^® MCM (10 %) as lipid phase, 0.6 % HPFG as emulsifier and HPFG 2.5 %, different grades colloidal silica (7.5 %) (Aerosil^® 300 Pharma, Aerosil^® 380 Pharma and Aeroperl^® 300 Pharma) as hydrophilic solid carriers was developed. The optimized HPFG-based silica lipid systems were characterized for physical characteristics like flow ability, compressibility, redispersiblity, solubility and in vitro drug release using USP apparatus II in pH 6.8 phosphate buffer. The system was also characterized for Fourier transform infrared spectroscopy, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The developed formulation was found to have excellent flow property, readily redispersiblity, better aqueous solubility and showed 3–4-fold increase in dissolution rate as compared to plain drug and marketed formulation (Simlo^® 10). Transition of crystalline drug to amorphous state was confirmed by DSC, PXRD and SEM studies. Enhanced dissolution rate and solubility possibly attributed to improved wetting, amorphous drug state and facilitated diffusion from lipid-based system. Thus developed HPFG-based silica lipid system provides an alternative means for SIM with enhanced dissolution rate and stability in oral solid dosage form.     

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

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

Solid dispersion adsorbates for enhancement of dissolution rates of drugs

Amalgamation of solid dispersion and melt adsorption technologies was utilized for enhancing the dissolution rate of poorly soluble drugs. Glibenclamide was employed as a model drug. PEG6000 and Gelucire44/14 were used as hydrophilic carriers for the preparation of solid dispersions, and lactose was utilized as an adsorbent for the preparation of solid dispersion adsorbates. A high dissolution rate of solid dispersion adsorbates was observed when compared to solid dispersions alone and one of the marketed products.     

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology

Abstract

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus^®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus^® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus^®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus^® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus^®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus^® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus^® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus^® and presents a basic understanding of Soluplus^® as a carrier of amorphous solid dispersions.     

Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with Gelucire 50/13

The objective of the study was enhancement of dissolution of poorly soluble carvedilol by solid dispersions (SDs) with Gelucire 50/13 using solvent evaporation method. The solubility of carvedilol showed linear increase with increasing concentrations of Gelucire indicating A_L type solubility diagrams. SDs characterized for physicochemical characteristics using differential scanning calorimetry and X-ray diffractometry revealed transformation of crystalline form of drug to amorphous form which was confirmed by scanning electron micrographs. Further fourier transform infrared spectroscopy results suggested there is no drug carrier interaction. From the dissolution parameters such as mean dissolution time, dissolution efficiency and drug release rate, improved dissolution characteristics for SDs were observed compared with physical mixture and pure drug. Thus SDs of carvedilol in Gelucire 50/13 showed enhanced solubility and dissolution rate compared to pure drug.     

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.     

Formulation of immediate release pellets containing famotidine solid dispersions

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. In this study, the dissolution of the drug was enhanced by a preparation of solid dispersion using two hydrophilic carriers, namely Gelucire 50/13 and Pluronic F-127. The prepared solid dispersions were characterized by differential scanning calorimetry (DSC), which indicated that there were no signs of interaction of the drug with the carriers used in the case of solid dispersions containing higher polymeric contents (1:3 and 1:5). FM solid dispersions in the matrices of Gelucire 50/13 and Pluronic F-127 (1:3) were used to prepare pellets. The scanning electron microscope (SEM) images of pellets showed that the pellets have spherical shape and their size depends on the carrier used. The dissolution of the drug from either solid dispersion or pellets was performed. The dissolution study depicted that, the presence of the drug in solid dispersion enhanced its dissolution in comparison with the drug itself. Also, the drug release from the manufactured pellets was found to be improved in the case of solid dispersions (drug:carrier 1:3). A complete drug release occurred after 30 min from pellets containing solid dispersions, while only about 30% of the loaded FM was released from pellets containing untreated drug after 2 h.     

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.     

Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation

The interest in hot-melt extrusion as a drug delivery technology for the production of solid dispersion is growing rapidly. Lumefantrine (LUMF) is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared. Appropriate selection of polymers, favoured the production of amorphous LUMF-polymer solid dispersions. The physicochemical properties of solid dispersions were characterized using scanning electron microscope, Infrared spectroscopy, differential scanning calorimetry and X-ray diffraction. LUMF SD showed enhanced dissolution rate attributed to amorphosization of LUMF. The IC50 value of LUMF SD formulations was found to be (0.084–0.213 ng/mL) i.e. 220–101 times lower than the IC50 value of pure LUMF (18.2 ng/mL) and 45–18 times lower than the IC50 value of standard antimalarial drug, chloroquine (3.8 ng/mL). Molecular dynamic simulation approach was used to investigate drug-polymer molecular interaction using computational modelling Schrodinger^® software. LUMF SD powder makes the Coartem^® therapy more operative with value-added beneficial comeback.     

Enhancement of solubility and dissolution of Coenzyme Q10 using solid dispersion formulation

This study aimed to develop a stable solid dispersion of Coenzyme Q₁₀ (CoQ₁₀) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ₁₀ having significantly enhanced solubility. Particularly, solid dispersion of CoQ₁₀ with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ₁₀ to the greatest extent. However, it exhibited poor stability and hence Aerosil^® 200 (colloidal silicon dioxide) was incorporated into the solid dispersion as an adsorbent to inhibit the recrystallization process. The solid dispersion of CoQ₁₀, poloxamer 407 and Aerosil^® 200 in the weight ratio of 1:5:6 exhibited improved stability with no significant change in solubility during the 1-month stability test. Moreover, the solid dispersion formulation containing Aerosil^® 200 significantly enhanced the extent of drug release (approx. 75% release) as well as the dissolution rate of CoQ₁₀. In conclusion, the present study has developed the stable solid dispersion formulation of CoQ₁₀ with poloxamer 407 and Aerosil^® 200 for the enhanced solubility and dissolution of CoQ₁₀, which could also offer some additional advantages including ease of preparation, good flowability and cost-effectiveness.     

Melt extrusion--an alternative method for enhancing the dissolution rate of 17beta-estradiol hemihydrate.

17Beta-estradiol hemihydrate (17beta-E2) is a poorly water-soluble drug. Physical methods for improving the solubility and dissolution rate, e.g. micronization, have certain inherent disadvantages. The method of choice in this study, melt extrusion, proved to overcome many of the shortcomings of conventional methods. Different compositions of excipients such as PEG 6000, PVP (Kollidon 30) or a vinylpyrrolidone-vinylacetate-copolymer (Kollidon VA64) were used as polymers and Sucroester WE15 or Gelucire 44/14 as additives during melt extrusion. The solid dispersions resulted in a significant increase in dissolution rate when compared to the pure drug or to the physical mixtures. For example, a 30-fold increase in dissolution rate was obtained for a formulation containing 10% 17beta-E2, 50% PVP and 40% Gelucire 44/14. The solid dispersions were then processed into tablets. The improvement in the dissolution behavior was also maintained with the tablets. The USP XXIII requirement for estradiol tablets reaching greater than 75% drug dissolved after 60 min was obtained in this investigation.     

Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules

Purpose. To investigate changes in drug dissolution on storage of ternary solid-dispersion granules containing poorly water-soluble drugs. Methods. Hot-melt granulation was used to prepare ternary solid-dispersion granules in which the drug was dispersed in a carrier and coated onto an adsorbent. Seven drugs including four carboxylic acid-containing drugs (BAY 12-9566, naproxen, ketoprofen, and indomethacin), a hydroxyl-containing drug (testosterone), an amide-containing drug (phenacetin), and a drug with no proton-donating group (progesterone) were studied. Gelucire 50/13 and polyethylene glycol (PEG) 8000 were used as dispersion carriers whereas Neusilin US2 (magnesium aluminosilicate) was used as the surface adsorbent. Results. Two competing mechanisms have been proposed to explain the complex changes observed in drug dissolution upon storage of solid dispersion granules. Conversion of the crystalline drug to the amorphous hydrogen bonded (to Neusilin) state seems to increase dissolution, whereas, the phenomenon of Ostwald ripening can be used to explain the decrease in drug dissolution upon storage. The solubility of the drug in Gelucire is a crucial factor in determining the predominant mechanism by governing the flux toward the surface of Neusilin. The mobility for this phenomenon was provided by the existence of the eutectic mixture in the molten liquid state during storage. Conclusions. A competitive balance between hydrogen bonding of the drugs with Neusilin and Ostwald ripening determines drug dissolution from solid-dispersion granules upon storage.     

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.     

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate

To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.     

Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability

Objectives Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Methods Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. Key findings SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Conclusions Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non‐absorbable base form.     

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.