Part II: bioavailability in beagle dogs of nimodipine solid dispersions prepared by hot-melt extrusion

The aim of the present work was to investigate the in vitro dissolution properties and oral bioavailability of three solid dispersions of nimodipine. The solid dispersions were compared with pure nimodipine, their physical mixtures, and the marketed drug product Nimotop. Nimodipine solid dispersions were prepared by a hot-melt extrusion process with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630), and ethyl acrylate, methyl methacrylate polymer (Eudragit EPO). Previous studies of XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates, two T(g)s were observed in the 30% and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N-H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion. The dissolution profiles of the three dispersion systems showed that the release was improved compared with the unmanipulated drug. Drug plasma concentrations were determined by HPLC, and pharmacokinetic parameters were calculated after orally administering each preparation containing 60 mg of nimodipine. The mean bioavailability of nimodipine was comparable after administration of the Eudragit EPO solid dispersion and Nimotop, but the HPMC and PVP/VA dispersions exhibited much lower bioavailability. However, the AUC(0-12 hr) values of all three solid dispersions were significantly higher than physical mixtures with the same carriers and nimodipine powder.     

Part I: characterization of solid dispersions of nimodipine prepared by hot-melt extrusion

The purpose of this study was to prepare and characterize solid dispersions of nimodipine with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630^®), and ethyl acrylate, methyl methacrylate polymer (Eudragit^® EPO). The goal was to investigate whether the solid dispersion prepared by hot-melt extrusion can improve the dissolution rate of nimodipine. The dissolution results indicated that three polymers are suitable carriers to enhance the in vitro dissolution rate of nimodipine in pH 4.5 medium. The solubility research and solubility parameters calculation was corresponded with dissolution data. XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates. NMD acted as a plasticizer for PVP/VA and EPO and was miscible with the polymers as well as 10% NMD-HPMC systems, because a single T_g was observed in these extrudates. However, two T_gs were observed in the 30 and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N-H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion.     

Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion

Using a mixture of Eudragit^® EPO and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) (Kollidon VA64) as carriers, a nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) to achieve high dissolution. The dissolution profiles in 900?mL 0.1?mol/L HCl showed that the drug release of NM-SD reached 90% in 1?h. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were used to characterize the state of NM. The results obtained showed that NM was in an amorphous form in the solid dispersion (SD). NM-SD tablets (NM-T-SD) were compressed by wet granulation and direct compression, respectively. The stability of NM-T-SD was examined during a 2-month storage period (40°C, RH 75%). The results showed that the dissolution of NM-T-SD was slightly reduced after 2 months storage (40°C, RH 75%), which implied that aging occurred to some degree. However, no NM crystals could be observed by PXRD after 2 months storage for NM-T-SD (F₁₁) prepared by direct compression.     

Preparation and Characterization of Solid Dispersions of Piroxicam with Hydrophilic Carriers

ABSTRACT

The objective of this study was to improve the dissolution rate of a poor water soluble drug, piroxicam, by solid dispersion technique. Solid dispersions were prepared by three different methods depending on the type of carrier. The dissolution rate of piroxicam was markedly increased in solid dispersion of myrj 52, Eudragit® E100 and mannitol. Solubility studies revealed a marked increase in the solubility of piroxicam with an increase in myrj 52 and Eudragit® E100 concentrations. Data from the X-ray diffraction and FT-IR spectroscopy showed that piroxicam was amorphous in the solid dispersions prepared with dextrin and Eudragit® E100.     

Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract

Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.     

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.     

Controlled Release of a Poorly Water-Soluble Drug from Hot-Melt Extrudates Containing Acrylic Polymers

ABSTRACT

Controlled release tablets containing a poorly water-soluble drug, indomethacin (IDM), acrylic polymers (Eudragit® RD 100, Eudragit® L 100, or Eudragit® S 100), and triethyl citrate (TEC) were prepared by hot-melt extrusion. The physicochemical and IDM release properties of the controlled release hot-melt extrudates were investigated. Indomethacin (IDM) was found to be both thermally and chemically stable following hot-melt extrusion processing and displayed a plasticizing effect on Eudragit® RL PO as demonstrated by a decrease in the glass transition temperatures of the polymer. The inclusion of either Pluronic® F68, Eudragit® L 100, or Eudragit® S 100 in the powder blend containing Eudragit® RD 100 prior to processing increased the rate of release of the IDM from the extrudates. An increase in the media pH and a decrease in the granule particle size also increased the rate of release of IDM. The inclusion of TEC up to 8% in the granule formulation or compressing the granules into tablets had no significant effect on the drug release rate. Indomethacin (IDM) was transformed from a crystalline Form I into an amorphous form in the Eudragit® RD 100 granules following hot-melt extrusion. The thermal processing facilitated the formation of a solid solution with a continuous matrix structure that was shown to control drug diffusion from the extrudates.     

Drug–polymer miscibility,interactions, and precipitation inhibition studies for the development of amorphous solid dispersions for the poorly soluble anticancer drug flutamide

The major goal of this research was to successfully formulate solid dispersion (SD) of the poorly soluble anticancer drug flutamide (FLT) using various hydrophilic polymers. Furthermore, to get more insight into SD, solid-state studies (miscibility and molecular interaction) were correlated with solution study (precipitation inhibition, dissolution). Hydrophilic polymers like PVP K90, HPMC, Eudragit EPO, and PEG 8000 were used at different drug-to-polymer w/w ratios. Solid-state miscibility studies were carried out using modulated differential scanning calorimetry (MDSC). SDs were prepared using solvent-evaporation technique and characterized by powder X-ray diffraction (PXRD) and MDSC. Infrared, Raman spectroscopy and molecular modeling were used to investigate drug-polymer interactions in the dispersions. Precipitation inhibition studies were carried out at various FLT-hydrophilic polymer ratios. Precipitation inhibition studies showed that PEG 8000 has the highest efficiency, followed by PVP K90, while HPMC and EPO showed no effect on precipitation inhibition. In the solid-state, MDSC of the physical mixture (PM) suggested that FLT is miscible to a greater extent with EPO and PEG 8000. Characterization of the amorphous dispersions using MDSC and PXRD concluded that FLT transformed from crystalline to amorphous form in the presence of PVP K90 and PEG 8000. Spectroscopic results confirmed stronger interaction of FLT with PVP K90 and PEG 8000, thereby confirming the in-solution precipitation and molecular modeling binding energy results. Amorphous dispersions formulated with PVP and PEG were stable and showed higher dissolution, an important property necessary to improve the physicochemical properties and drug delivery of poorly soluble anticancer drug FLT.     

Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion

Using a mixture of Eudragit EPO and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) (Kollidon VA64) as carriers, a nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) to achieve high dissolution. The dissolution profiles in 900 mL 0.1 mol/L HCl showed that the drug release of NM-SD reached 90% in 1h. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were used to characterize the state of NM. The results obtained showed that NM was in an amorphous form in the solid dispersion (SD). NM-SD tablets (NM-T-SD) were compressed by wet granulation and direct compression, respectively. The stability of NM-T-SD was examined during a 2-month storage period (40 degrees C, RH 75%). The results showed that the dissolution of NM-T-SD was slightly reduced after 2 months storage (40 degrees C, RH 75%), which implied that aging occurred to some degree. However, no NM crystals could be observed by PXRD after 2 months storage for NM-T-SD (F11) prepared by direct compression.     

Evaluation of different screening methods to understand the dissolution behaviors of amorphous solid dispersions

Objective: The objectives of the current study were to understand the dissolution behaviors of amorphous solid dispersions (ASD) using different screening methods and their correlation to the dissolution of formulated products.

Materials and methods: A poorly soluble compound, compound E, was used as a model compound. ASDs were prepared with HPMC, Kollidon VA64 and Eudragit EPO using hot-melt extrusion. Different techniques including precipitation, powder, capsule and compact dissolution and the dissolution of formulated products were conducted in USP simulated gastric fluid using a USP II dissolution apparatus.

Results and discussions: It was found that a precipitation study could generally predict powder, capsule and compact dissolution. Yet, it was recommended to run the dissolution at a higher paddle speed or for a longer duration to improve the predictability. It was also recommended to run powder, capsule and compact dissolution at both slow and high speeds to gain insights into wetting, dispersion and the dissolution of a system. Sometimes, capsule or compact dissolution could not be predicted by precipitation or powder dissolution due to plug formation. In this case, properly designed dosage forms were needed to break up this plug to optimize the dissolution profiles. On the contrary, formulations and dissolution conditions would have minimal effects on the dissolution profiles of a fast-dissolving solid dispersion.

Conclusions: Different techniques are available to select the right polymers to optimize dissolution behaviors. However, it is important to understand the merits and limitations of each technique in order to optimize the formulations for amorphous solid dispersions.     

Flocculated amorphous itraconazole nanoparticles for enhanced in vitro supersaturation and in vivo bioavailability

Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit^® L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH. The formation of open flocs by diffusion limited aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of the flocculated nanoparticles at pH 6.8, the particle size was modestly larger than the original size, on the order of 1 μm. High in vitro supersaturation (AUC) of the flocculated nanoparticle dispersions was observed in micellar media at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach, relative to the AUC for a commercially available Itz formulation, Sporanox. Greater in vivo bioavailability in rats was correlated directly to the higher in vitro AUC at pH 6.8 with micelles during the pH shift experiment for the flocculated nanoparticle dispersions relative to Sporanox. The ability to generate and sustain high supersaturation in micellar media at pH 6.8, as shown with the in vitro pH shift dissolution test, is beneficial for increasing bioavailability of Itz by oral delivery.     

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen

Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.

Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.

Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.

Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (C_max) of 9140.84?±?614.36?ng/ml at 3?h T_max and solid dispersion tablets showed C_max?=?11?445.46?±?149.23?ng/ml at 2?h T_max. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.

Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.     

Determination of precipitation inhibitory potential of polymers from amorphous solid dispersions

Abstract

Precipitation inhibitory potential of polymers screened from precipitation study may be altered once it is formulated in amorphous solid dispersions (ASDs).

Objective: Present study was embarked with an objective to determine whether the polymers retain the same inhibitory potential after formulating them into ASDs.

Methods: Screening of polymers was based on a new dimensionless parameter ‘Supersaturation Holding Capacity (SHC)’ calculated from the precipitation study. Nifedipine ASDs were formulated using HPMC E3 and HPMC E50 (high SHC values), and HPMC K100M, PVP K25, and HPC M (low to moderate SHC values). Generated ASDs were characterized by DSC, FTIR, and PXRD and evaluated for stability under accelerated conditions (40?C and 75% RH) for 6 months.

Results: Thermal analysis of the ASDs and theoretical prediction of the glass transition temperature (T_g) suggested a linear dependency of T_g on the content of HPMC E3 and HPMC E50. Under accelerated stability conditions, all ASDs of nifedipine with HPMC E3 and HPMC E50 (except ASDs with 70% drug load) were stable, which could be attributed to the molecular level dispersion of the drug in these polymers. SHC parameter calculated from the apparent solubility profile gave following rank order HPMC E50 (3.4)?>?HPMC E3 (3.2)?>?HPMC K100M (1.29)?>?PVP K25 (1.09)?>?HPC M (0.99). SHC calculated from the apparent solubility profile of ASDs demonstrated good agreement between the solution state and solid state screening of the polymers for precipitation inhibition. During dissolution study, nearly four-fold enhancement has been observed with ASDs comprising HPMC E3 and HPMC E50.

Conclusions: The outcome of the study concluded that SHC can be a promising parameter in the screening of polymers for the development of the ASDs.     

Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by solid dispersion utilizing fourth generation carrier

Context: Naringenin (NRG), the aglycone flavonoid present in grapefruits, possesses anti-inflammatory, anti-carcinogenic, anti-lipid peroxidation and hepato-protective effects. However, it is poorly soluble in water and exhibits slow dissolution after oral ingestion, thus restricting its therapeutic efficacy.

Objective: With the aim to enhance the dissolution rate and oral bioavailability of NRG, solid dispersion technique has been applied using Soluplus® as carrier.

Methods: Solid dispersions of NRG were prepared by solvent evaporation and kneading methods using various ratios (1:4, 3:7, 2:3 and 1:1) of NRG:Carrier. Characterization of the optimized formulations was performed using Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The in vivo behavior of the optimized formulations was also investigated in Wistar Albino rats.

Results: NRG solid dispersion showed a significantly higher solubility and drug dissolution rate than pure NRG (p?Conclusion: Based on these results, it was concluded that solid dispersion technique markedly enhances the in vitro drug release and in vivo behavior of the grapefruit flavonoid NRG.     

Classification of solid dispersions: correlation to (i) stability and solubility (ii) preparation and characterization techniques

Solid dispersion has been a topic of interest in recent years for its potential in improving oral bioavailability, especially for poorly water soluble drugs where dissolution could be the rate-limiting step of oral absorption. Understanding the physical state of the drug and polymers in solid dispersions is essential as it influences both the stability and solubility of these systems. This review emphasizes on the classification of solid dispersions based on the physical states of drug and polymer. Based on this classification, stability aspects such as crystallization tendency, glass transition temperature (T_g), drug polymer miscibility, molecular mobility, etc. and solubility aspects have been discussed. In addition, preparation and characterization methods for binary solid dispersions based on the classification have also been discussed.     

Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems

Context: Piperine alkaloid, an important constituent of black pepper, exhibits numerous therapeutic properties, whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability.

Objective: Herein, a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison.

Methods: The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated.

Results: The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89%, respectively after 2?h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine.

Conclusion: Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.     

Lonidamine Solid Dispersions: In Vitro and In Vivo Evaluation

ABSTRACT

Solid dispersions of lonidamine in PEG 4000 and PVP K 29/32 were prepared by the spray-drying method. Then, the binary systems were studied and characterized using differential scanning calorimetry, hot stage microscopy, and x-ray diffractometry. In vitro dissolution studies of the solid dispersed powders were performed to verify if any lonidamine dissolution rate or water solubility improvement occurred. In vivo tests were carried out on the solid dispersions and on the cyclodextrin inclusion complexes to verify if this lonidamine water solubility increase was really able to improve the in vivo drug plasma levels. Drug water solubility was increased by the solid dispersion formation, and the extent of increase depended on the polymer content of the powder. The greater increase of solubility corresponded to the highest content of polymer. Both the solid dispersions and the cyclodextrin complexes were able to improve the in vivo bioavailability of the lonidamine when administered per os. Particularly, the AUC of the drug plasma levels was increased from 1.5 to 1.9-fold depending on the type of carrier.     

Effect of polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer on bioadhesion and release rate property of eplerenone pellets

Abstract

The present study involved the design and development of oral bioadhesive pellets of eplerenone. A solid dispersion of eplerenone was developed with a hydrophilic carrier, polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®). Bioadhesive pellets were prepared from this solid dispersion using a combination of HPMC K4M and Carbopol 934P. Both the solid dispersion and the pellets were evaluated for various physicochemical properties such as solubility, entrapment efficiency, drug content, surface morphology, mucoadhesion and swelling behavior. Analysis carried out using FT-IR, DSC and XRD found no interaction between the eplerenone and excipients. The solid dispersion had irregular-shaped smooth-surfaced particles of diameter 265?±?105.5?μm. In TEM analysis, eplerenone particles of size 79–120?nm were found. The solubility and dissolution of eplerenone in the Soluplus^®-based solid dispersion were 5.26 and 2.50 times greater, respectively. Investigation of the swelling behavior of the pellets showed that the thickness of the gel layer increased continuously over the duration of the study. Moreover, a correlation was observed between the thickness and strength of the gel layer and the percentage release. The mechanism of drug release was found to be non-Fickian (anomalous), with the release kinetics approaching first-order kinetics. The bioavailability of the eplerenone bioadhesive pellet formulation was studied using Wistar rats and was found to be improved. An in vivo mucoadhesion study showed that the pellets are retained for 24?h in rabbits. It was concluded that Soluplus^® had a positive effect on the solubility and dissolution of pellets without affecting the bioadhesion.     

Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug

Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus^®, a low T_g amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110?°C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC_0–24h) and peak plasma concentration (C_max) were four times higher for the modified solid dispersion compared to that of pure artemisinin.     

Production of advanced solid dispersions for enhanced bioavailability of itraconazole using KinetiSol® Dispersing

Objectives: To investigate the ability of KinetiSol® Dispersing to prepare amorphous solid dispersions of itraconazole using concentration-enhancing polymers. Methods: Concentration-enhancing nature of several cellulosic polymers (HPMC, hypromellose acetate succinate) was studied using a modified in vitro dissolution test. Solid dispersions were prepared by KinetiSol® Dispersing and characterized for solid-state properties using X-ray diffraction and differential scanning calorimetry. Potency and release characteristics were also assessed by high-performance liquid chromatography. Oral bioavailability of lead formulations was also assessed in animal models. Results: Screening studies demonstrated superior concentration-enhancing performance from the hypromellose acetate succinate polymer class. Data showed that stabilization was related to molecular weight and the degree of hydrophobic substitution on the polymer such that HF > MF ≈ LF, indicating that stabilization was achieved through a combination of steric hindrance and hydrophobic interaction, supplemented by the amphiphilic nature and ionization state of the polymer. Solid dispersions exhibited amorphous solid-state behavior and provided neutral media supersaturation using a surfactant-free pH change method. Rank-order behavior was such that LF > MF > HF. Addition of Carbopol 974P increased acidic media dissolution, while providing a lower magnitude of supersaturation in neutral media because of swelling of the high viscosity gel. In vivo results for both lead compositions displayed erratic absorption was attributed to the variability of gastrointestinal pH in the animals. Conclusions: These results showed that production of amorphous solid dispersions containing concentration-enhancing polymers through KinetiSol® Dispersing can provide improved oral bioavailability; however, additional formulation techniques must be developed to minimize variability associated with natural variations in subject gastrointestinal physiology.