Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben^® product.     

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.     

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T_g) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T_g from the predicted values calculated using the Couchman–Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.     

Improved stability of solid dispersions of manidipine with polyethylene glycol 4000/copovidone blends: application of ternary phase diagram

Context: Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility.

Objective: The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability.

Methods: Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances. The pulverized powder of solid dispersions was then determined, for their physicochemical properties, by differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and dissolution of MDP from the tSD were investigated. The physical stability of tSD was also determined under accelerated condition at 40?°C/75% relative humidity (RH) for 6 months.

Results and discussion: The results showed that MDP was molecularly dispersed in PEG4000 and copovidone when the tSD was created from homogeneous region of solid ternary phase diagram. FTIR results confirmed that strong hydrogen bonding was presented between MDP and copovidone, leading to a significant increase in the solubility and dissolution of MDP. After storage at accelerated condition (40?°C/75%RH) for 6 months, the tSD still showed a good appearance and high solubility.

Conclusion: The results of this study suggest that tSD prepared by melting has promising potential for oral administration and may be an efficacious approach for improving the therapeutic potential of MDP.     

Influence of different polymers on crystallization tendency and dissolution behavior of cilnidipine in solid dispersions

Context: Cilnidipine (CN) is a novel dihydropyridine calcium antagonist that is practically insoluble in aqueous media and exhibits a low oral bioavailability or limited clinical efficacy.

Objective: This study investigated the effects of three commercial and chemically diverse polymers – PVP, PVP/VA and Soluplus – on crystallization tendency and in vitro dissolution profiles of CN in order to determine an optimum carrier for composing the preferred solid dispersion (SD) of CN.

Methods: All these co-evaporated systems were characterized up to 3 months by thermoanalytical (DSC), crystallographic (POM, PXRD), microscopic (SEM) and spectroscopic (FTIR) techniques.

Results: The results showed that the polymers could be sorted by their effects of inhibiting CN crystallization in the ascending order: Soluplus, PVP/VA, PVP. The sequence was in accordance with that of the strength of drug–polymer hydrogen bonds revealed by FTIR spectra. It could be ascribed to relative hydrogen-bonding acceptor strengths of N-vinylpyrrolidone moiety in the polymer molecules. On the other hand, all the SDs showed enhanced dissolution profiles compared to pure CN alone. On their effects of enhancing CN dissolution, the polymers could be sorted in the descending order: Soluplus, PVP, PVP/VA.

Conclusions: It implied that the dissolution behavior of CN could bear a close relationship to both hydration capacity and hydrogen-bonding interaction tendency of moieties of the polymers. It might suggest an optimal formulation for CN comprising both PVP and Soluplus.     

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.     

Corroboration of naringin effects on the intestinal absorption and pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ rat models

Objective: The aim of this study was to corroborate the effects of naringin, a P-glycoprotein inhibitor, on the intestinal absorption and pharmacokinetics of candesartan (CDS) from candesartan cilexetil (CAN) solid dispersions using in-situ rat models.

Materials and methods: Intestinal transport and absorption studies were examined by in-situ single pass perfusion and closed-loop models. We evaluated the intestinal membrane damage in the presence of naringin by measuring the release of protein and alkaline phosphatase (ALP).

Results and discussion: We noticed 1.47-fold increase in P_eff of CDS from freeze-dried CAN-loaded solid dispersions with naringin (15?mg/kg, w/w) when compared with freeze-dried solid dispersion without naringin using in-situ single pass intestinal perfusion model. However, no intestinal membrane damage was observed in the presence of naringin. Our findings from in-situ closed-loop pharmacokinetic studies showed 1.34-fold increase in AUC with elevated C_max and shortened t_max for freeze-dried solid dispersion with naringin as compared to freeze-dried solid dispersion without naringin.

Conclusion: This study demonstrated that increased solubilization (favored by freeze-dried solid dispersion) and efflux pump inhibition (using naringin), the relative bioavailability of CDS can be increased, suggesting an alternative potential for improving oral bioavailability of CAN.     

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.     

Dissolution rate enhancement,in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions.     

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.     

绿原酸磷脂复合物固体分散体的体外溶出和药动学研究

为研究绿原酸磷脂复合物固体分散体(CA-PC-SD)的体外溶出以及体内药动学规律,采用HPLC法考察CA-PC-SD的体外溶出,大鼠灌胃后测定其血药浓度,并采用DAS 2.0软件分析计算药动学参数.结果显示:CA-PC-SD显著改善绿原酸磷脂复合物(CA-PC)的溶出效果,相较于原料药(CA)其相对生物利用度提高2.12倍.表明CA-PC-SD能显著改善CA-PC的体外溶出特性以及CA的口服生物利用率.     

Miscibility behavior and formation mechanism of stabilized felodipine-polyvinylpyrrolidone amorphous solid dispersions

In the present study, solid dispersion systems of felodipine (FEL) with polyvinylpyrrolidone (PVP) were developed, in order to enhance solid state stability and release kinetics. The prepared systems were characterized by using Differential Scanning Calorimetry, X-Ray Diffraction, and Scanning Electron Microscopy techniques, while the interactions which take place were identified by using Fourier Transformation-Infrared Spectroscopy. Due to the formation of hydrogen bonds between the carbonyl group of PVP and the amino groups of FEL, transition of FEL from crystalline to amorphous state was achieved. The dispersion of FEL was found to be in nano-scale particle sizes and dependent on the FEL/PVP ratio. This modification leads to partial miscibility of the two components, as it was verified by DSC and optimal glass dispersion of FEL into the polymer matrix since no crystalline structure was detected with XRD. The above deformation has a significant effect on the dissolution enhancement and the release kinetics of FEL, as it causes the pattern to change from linear to logarithmic. An impressive optimization of the dissolution profile is observed corresponding to a rapid release of FEL in the system containing 10% w/w of FEL, releasing 100% in approximately 20 min. The particle size of dispersed FEL into PVP matrix could be classified as the main parameter affecting dissolution optimization. The mechanism of such enhancement consists of the lower energy required for the dissolution due to the amorphous transition and the fine dispersion, which leads to an optimal contact surface of the drug substance with the dissolution media. The prepared systems are stable during storage at 40 ± 1°C and relative humidity of 75 ± 5%. Addition of sodium docusate as surfactant does not affect the release kinetics, but only the initial burst due to its effect on the surface tension and wettability of the systems.     

Solid State and Dissolution Rate Characterization of Co-Ground Mixtures of Nifedipine and Hydrophilic Carriers

ABSTRACT

Co-ground powders of the poorly water-soluble drug nifedipine and a hydrophilic carrier, [partially hydrolyzed gelatin (PHG), polyvinylpyrrolidone (PVP), sodium dodecyl sulfate (SDS), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), urea or Pluronic F108] were prepared in order to improve the dissolution rate of nifedipine. The effects of type of grinding equipment, grinding time, and type of hydrophilic carrier on the crystallinity of nifedipine (x-ray diffraction and differential scanning calorimetry) on the interaction between drug and carriers (differential scanning calorimetry), on the particle size and appearance (scanning electron microscopy), on the wettability (contact angle measurements), and on the drug release were investigated. Grinding nifedipine together with these carriers improved the dissolution rate. PHG-ground mixtures resulted in the fastest dissolution rate followed by PVP, SDS, HPMC, Pluronic, urea, and PEG. This effect was not only due to particle size reduction, which increased in the order PHG < PEG = SDS < Pluronic < drug < urea < HPMC < PVP, but also resulted from the ability of some carriers (PVP and HPMC) to prevent reaggregation of the finely divided drug particles. PVP, HPMC, and PHG formed a powder with amorphous drug. The carriers improved the wettability of the ground products in the order HPMC < drug < urea < PVP < SDS < PHG < PEG < Pluronic. Differential scanning calorimetry (DSC) measurements gave valuable information about the nature of drug crystallinity and the interactions with the carriers within the ground mixtures.     

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.     

Enhanced Dissolution of Ibuprofen Using Solid Dispersion with Polyethylene Glycol 20000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility and in vitro drug release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs in DSC study indicated the possibilities of drug–polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C_max, and a significant decrease in T_max over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low-temperature melting method using polyethylene glycol 20000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.     

Preparation of budesonide-poly (ethylene oxide) solid dispersions using supercritical fluid technology

The purpose of this study was to investigate the possibility of preparing solid dispersions of the poorly soluble budesonide by supercritical fluid (SCF) technique, using poly (ethylene oxide) (PEO) as a hydrophilic carrier. The budesonide-PEO solid dispersions were prepared, using supercritical carbon dioxide (SC CO₂) as the processing medium, and characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility test and dissolution test in order to understand the influence of the SCF process on the physical status of the drug. The endothermic peak of budesonide in the SCF-treated mixtures was significantly reduced, indicating that budesonide was in amorphous form inside the carrier system. This was further confirmed by SEM and PXRD studies. The enhanced dissolution rates of budesonide were observed from SCF-treated budesonide-PEO mixtures. The amorphous characteristic of the budesonide, the better mixing of drug and PEO powders in the presence of SC CO₂, together with the improved wettability of the drug in PEO, produced a remarkable enhancement of the in vitro drug dissolution rate. Thus, budesonide-PEO solid dispersions with enhanced dissolution rate can be prepared using organic solvent-free SCF process.     

Thermal behavior and dissolution properties of naproxen from binary and ternary solid dispersions

Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000, 6000, or 20,000) as a carrier with or without incorporation of anionic (sodium dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by the melting method. Physicochemical characteristics were determined by differential scanning calorimetry (DSC) and X-ray diffraction analysis. The results of dissolution studies showed that drug dissolution properties were better from ternary systems than from binary systems since in the former the wetting and solubilizing effects of surfactant and polymer were additive. No influence of the PEG molecular weight was found. The best performance given by anionic surfactant has been attributed to several factors, such as higher hydrophilicity, better solubilizing power, and most facile interaction with both drug and PEG. No important changes in solid-state characteristics or in drug dissolution properties were found after 30 months storage for dispersions with or without surfactant. Only a slight decrease in initial drug dissolution rate was observed at the highest concentration (10% w/w) of SDS.     

The incorporation of low-substituted hydroxypropyl cellulose into solid dispersion systems

While the use of amorphous solid dispersions to improve aqueous solubility is well documented, little consideration has traditionally been given to the finished dosage form. The objective of this study was to evaluate the dissolution performance of amorphous solid dispersions containing a dispersed superdisintegrant with binding properties. KinetiSol® dispersing was used to thermally process hypromellose acetate succinate-based compositions containing the drug substance nifedipine (NIF) and a highly compressible grade of low-substituted hydroxypropyl cellulose (New Binder Disintegrants; NBD-grade). Solid-state analysis demonstrated that compositions were rendered amorphous during processing. Tablets containing intra-dispersion NBD were found to exhibit non-sink dissolution performance similar to milled intermediate, demonstrating excellent disintegration characteristics. Conversely, tablets without intra-dispersion NBD were found to release significantly less NIF during dissolution analysis due to particle agglomeration. It was determined that compressibility and particle wetting increased as the level of intra-dispersion NBD increased.     

Tailoring the release rates of fluconazole using solid dispersions in polymer blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

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.