Preparation of functional composite particles of salbutamol sulfate using a 4-fluid nozzle spray-drying technique

A previous study on spray-drying demonstrated that it could promote the solubility of poorly water-soluble drugs using water-soluble polymers. Here, the preparation of composite particles of salbutamol sulfate (Sb) with water-insoluble polymers, such as Eudragit RS (RS) or Eudragit RL (RL) as a carrier, was examined. Despite the water insolubility of both polymers, the permeability of water was low in the former but high in the latter. We attempted to prepare controlled release composite particles by exploiting the characteristics of these carriers. The composite particles of the three components (Sb, RS, and RL) were prepared using a 4-fluid nozzle spray-dryer, and their physico-chemical and dissolution properties were compared with physical mixtures. Examination of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray-drying process had atomized to several microns and were spherical. Analysis by X-ray diffraction and differential scanning calorimetry revealed that diffraction peaks and heat of fusion of Sb in the spray-dried samples decreased, indicating that the drug was amorphous and formed a solid dispersion. FT-IR analysis suggested that the amino group of Sb and a carbonyl group of the polymers formed a hydrogen bond. A dissolution test of Sb-RS-RL particles prepared using the 4-fluid nozzle spray-drying method showed that release rates were depressed significantly compared to the physical mixture at pH 1.2 and 6.8, and the depression was greater when RS was used instead of RL, presumably because of the permeability difference. The compression of these particles into tablets revealed that desirable controlled released dosage forms could be prepared. In addition, Sb was used to simulate an anti-asthmatic drug. For this an Andersen cascade impactor for dry powder inhalers was used to investigate delivery to the lungs.     

Improved dissolution of an insoluble drug using a 4-fluid nozzle spray-drying technique

A solid dispersion of the drug can be made using a polymer carrier to improve solubility. Generally, drugs become amorphized when solid dispersion is formed using a polymer carrier. In such high energy conditions, the solubility of the drug molecule is increased. We previously prepared solid dispersion using a spray-drying technique and reported its solubility and crystallinity. In this study, hydroxypropylmethylcellulose (HPMC) was used as the carrier, and tolubutamide was the model drug, which is water-insoluble. Solubility was evaluated by preparing a solid dispersion using a newly developed 4-fluid nozzle spray dryer. Observation of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray drying were atomized to several microns, and they had also become spherical. Assessment of the crystallinity of the spray-dried particles by powder X-ray diffraction and differential scanning calorimetry demonstrated that the tolbutamide had been amorphized, forming a solid dispersion. The apparent release rate constant K of the drug from the spray-dried particles was 4 to 6 times faster than the original drug in pH 1.2, and it was also 1.5 to 1.9 times faster than the original drug in pH 6.8. The 70% release time (T(70)) of the drug from the spray-dried particles was 20 to 30 times faster than the original drug in pH 1.2 solution as well as 2 to 3 times faster than the original drug in pH 6.8 solution. Pharmaceutical preparations prepared in this way using the 4-fluid nozzle system spray dryer formed composite particles, resulting in a remarkably improved dissolution rates of the drug.     

Improvement of the dissolution rate of nitrendipine using a new pulse combustion drying method

Solid dispersions (SDs) of nitrendipine (NTD), a poorly water-soluble drug, were prepared with the Hypulcon pulse combustion dryer system, and the physicochemical properties of particles were investigated and compared with those of particles prepared with a spray dryer. The SD particles prepared with Hypulcon using Aerosil and Tween 80 as carriers showed improved properties over those prepared with a conventional spray dryer, such as smaller particle size, tighter particle size distribution, and no agglomeration. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that the drug in the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution was dispersed in an amorphous state. Fourier transformation IR spectroscopy indicated the presence of hydrogen bonds between NTD and Aerosil. Aerosil had greater ability to improve the dissolution of NTD than Sylysia and other polymers. The highest drug supersaturation concentration was maintained continuously during the dissolution test of the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution using Hypulcon. The good hydrophilicity and dispersibility of Aerosil, solubilization of Tween 80, and actions of shock waves and ultrasonic waves might account for the amorphization of NTD and improved dissolution rate of SDs. Pulse combustion drying with low drying costs and high thermal efficiency is a promising method for the preparation of SD particles with improved properties without using organic solvent.     

Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion

The main aim of this study was to enhance the dissolution rate of a poorly water-soluble antioxidant drug, quercetin, by fabricating its nanoparticles, complexes and solid dispersions using evaporative precipitation of nanosuspension (EPN). We studied the influence of the type of antisolvent, drug concentration and solvent to antisolvent ratio on the quercetin particles formed during EPN. With water as antisolvent, the particles were big, irregular and flake type but with benzene or hexane as antisolvent, the particles were smaller and needle type. Smallest particles of 220 nm diameter were achieved with hexane as antisolvent, lowest drug concentration and highest solvent to antisolvent ratio. The relative dissolution values showed that the dissolution rate of the EPN prepared quercetin nanoparticles was much higher than that of the raw drug. Quercetin formed inclusion complexes with β-cyclodextrin, and solid dispersions with polyvinylpyrrolidone and pluronic F127, where quercetin was present in an amorphous form and/or was dispersed at a molecular level. The dissolution rate of quercetin in its complexes and solid dispersions improved significantly from the raw quercetin as indicated by the percent dissolution efficiency. It was interesting to note that at lower carrier concentration, the solid dispersions of quercetin with polyvinylpyrrolidone and pluronic F127 presented better dissolution than its complex with β-cyclodextrin but at higher carrier concentration, there was no significant difference in the dissolution behavior of the three formulations. Using Korsmeyer-Peppas model, diffusion was found to be the main release mechanism.     

Particle design of three-component system for sustained release using a 4-fluid nozzle spray-drying technique

We prepared composite particles of acetaminophen (Act) with chitosan (Cht) and hydroxypropylmethylcellulose phthalate (HPMCP) as a carrier using a newly developed 4-fluid nozzle spray-dryer. Cht dissolves in acid solutions and forms a gel, but it is insoluble in alkaline solutions. On the other hand, HPMCP is insoluble in acid solutions, but it dissolves in alkaline solutions. Therefore, we tested a preparation of controlled release composite particles using the characteristics of these carriers. Act and Cht mixtures in prescribed ratios were dissolved in an acid solution. Composite particles of Act and HPMCP in prescribed ratios were dissolved in alkaline solutions. We evaluated the composite particles of the three components (Act, Cht, and HPMCP) by preparing solid dispersions using a 4-fluid nozzle spray-dryer. Observation of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray-drying process had atomized to several microns and had all become spherical. We investigated the physical properties of the composite particles by powder X-ray diffraction, differential scanning calorimetry, and dissolution rate analysis to clarify the effects of crystallinity on the dissolution rate. Powder X-ray diffraction peaks and the heat of fusion of Act in the spray-dried samples decreased in proportion to the carrier content, indicating that the drug was amorphous. These results indicate that the Act-Cht-HPMCP system formed a solid dispersion. Furthermore, we investigated the interaction between the drug and the carrier using FT-IR analysis. FT-IR spectroscopy of the Act solid dispersions suggested that the Act carbonyl and Cht amino groups formed a hydrogen bond. On the other hand, interaction by hydrogen bond was observed between the carbonyl group of HPMCP with the amino group of Act. In the three-component Act-Cht-HPMCP system, the 4-fluid nozzle spray-dried preparation with a mixing ratio of 1 : 2.5 : 2.5 obtained sustained release preparation in all pH test solutions.     

Enhanced dissolution of oxcarbazepine microcrystals using a static mixer process

The purpose of this study was to form micronized powders of Oxcarbazepine (OXC), a poorly water-soluble drug, using a static mixer technique to enhance the dissolution rate. Controlled precipitation was achieved injecting the organic OXC solution rapidly into an aqueous methylcellulose (MC) protective solution by means of a static mixer thus providing turbulent and homogeneous mixing. Furthermore, a factorial design was implemented for data analysis. The physicochemical properties of the freeze-dried dispersions were evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Drug microcrystals showed a narrow size distribution with approximately 2 μm mean particle size and high drug loading. DSC and FTIR studies revealed that the drug remained in crystalline state and no drug–polymer interaction occurred. The dissolution studies showed enhanced dissolution of OXC microcrystals compared to the pure drug. The static mixer technique was proved capable for micro-sized polymeric particles. This is an inexpensive, less time consuming and fully scalable process for development of poorly soluble drugs.     

Particle design using a 4-fluid-nozzle spray-drying technique for sustained release of acetaminophen

We prepared matrix particles of acetaminophen (Act) with chitosan (Cht) as a carrier using a newly developed 4-fluid-nozzle spray dryer. Cht dissolves in acid solutions and forms a gel, but it does not dissolve in alkaline solutions. Therefore, we tested the preparation of controlled release matrix particles using the characteristics of this carrier. Act and Cht mixtures in prescribed ratios were dissolved in an acid solution. We evaluated the matrix particles by preparing a solid dispersion using a 4-fluid-nozzle spray dryer. Observation of the particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray drying process had atomized to several microns, and that they had become spherical. We investigated the physicochemical properties of the matrix particles by powder X-ray diffraction, differential scanning calorimetry, and dissolution rate analyses with a view to clarifying the effects of crystallinity on the dissolution rate. The powder X-ray diffraction peaks and the heat of the Act fusion in the spray-dried samples decreased with the increase of the carrier content, indicating that the drug was amorphous. These results indicate that the system formed a solid dispersion. Furthermore, we investigated the interaction between the drug and carrier using FT-IR analysis. The FT-IR spectroscopy for the Act solid dispersions suggested that the Act carboxyl group and the Cht amino group formed a hydrogen bond. In addition, the measurement results of the 13C CP/MAS solid-state NMR, indicated that a hydrogen bond had been formed between the Act carbonyl group and the Cht amino group. In the Act-Cht system, the 4-fluid-nozzle spray-dried preparation with a mixing ratio of 1 : 5 obtained a sustained release preparation in all pH test solutions.     

Influence of particle design on oral absorption of poorly water-soluble drug in a silica particle-supercritical fluid system

The physicochemical characteristics and oral absorption of a poorly water-soluble drug, K-832, adsorbed onto porous silica (Sylysia 350), were compared with those of K-832 adsorbed onto non-porous silica (Aerosil 200). K-832 and silica were treated with supercritical CO(2) (scCO(2)) to produce K-832-Sylysia 350 and K-832-Aerosil 200 formulations. Scanning electron microscopy, polarizing microscopy, powder X-ray diffraction, and differential scanning calorimetry results suggested that K-832 mainly existed in an amorphous state in both formulations. The specific surface area of both formulations was much larger than that of pure K-832 crystals. The dissolution rate of K-832 from both formulations was considerably greater than that from corresponding physical mixtures due to rapid wetting of the hydrophilic carrier surfaces and amorphous state, the dissolution from the K-832-Sylysia 350 formulation being the fastest. In vivo absorption tests on the two formulations indicated no significant differences in their peak concentration (C(max)) and the area under their plasma concentration-time curve (AUC), while the concentrations of K-832 in the K-832-Sylysia 350 formulation were significantly higher than those in the K-832-Aerosil 200 formulation 1 h and 1.5 h after administration of these formulations (p<0.05). This could be attributed to the different dispersion states of K-832 in the formulations due to their different three-dimensional structures (porous and non-porous). In physical stability tests, the amorphous drugs in both formulations were stable at room temperature for at least 14 months. Thus, the absorption of poorly water-soluble drugs could be greatly improved by adsorption onto porous silica using scCO(2).     

Multidrug encapsulation by coaxial tri-capillary electrospray

This study describes how a coaxial tri-capillary electrospray (ES) system can synthesize monodisperse PLGA-coated particles containing multiple drugs in one step. The coaxial arrangement of three separate capillaries in an ES nozzle enables production of composite particles with tri-layered structures without the complicated steps involved in emulsion processes. Various materials can be encapsulated in separate layers of individual composite particles without regard for the hydroscopic property of drugs. At the proper spray setting, nearly 100% drug encapsulation efficiency can be achieved. By varying the feed flowrate of spray solutions, the overall particle sizes, ranging from submicrometer to micrometer, and the thickness of the layers in produced particles can also be controlled. Size and tri-layered structure of the composite particles were characterized by SEM and laser scanning confocal microscopy (LSCM). We further explored the spray technique in the production of tri-layered composite particles having a controlled multidrug-release profile, and compared the release profiles of both core–shell structured particles (produced by coaxial dual-capillary ES) and tri-layered ones (produced by coaxial tri-capillary ES). The comparison showed that composite particles with the tri-layered structure can release multiple drugs in distinct kinetic phases. We further demonstrated that the release profile of tri-layered composite particles can be effectively controlled by varying the thickness and chemical composition of their individual layers.     

Improvement of dissolution property of poorly water-soluble drug by novel dry coating method using planetary ball mill

The dissolution property of a poorly water-soluble drug, flurbiprofen (FP), was improved by a novel dry coating method using a planetary ball mill. Several mixtures composed of water-soluble additives (D-mannitol, lactose, and erythritol), light anhydrous silicic acid, and flurbiprofen were prepared. These mixtures and several starches were co-ground in a planetary ball mill, and the surface of the starches was dry coated with the mixtures. The size, appearance, yield, and drug dissolution property of the dry coated preparations were evaluated, and the optimal formulation which improved the dissolution property of poorly water-soluble flurbiprofen was determined. The dissolution rate of FP was increased by dry coating of the surface of starches with microparticulated FP. It was further increased by co-grinding of FP, starch, and a water-soluble additive, or dry coating of the starch surface with microparticulated FP and light anhydrous silicic acid, as a glidant. These co-ground and dry coated preparations could be recovered from the pot of the planetary ball mill readily without adhesion to the inside wall of the pot. These are considered to be novel, industrially applicable methods for improving the dissolution rate of poorly water-soluble drugs.     

Structural Characterization of Composite Particles of Two Commonly Used Herbicides

A spray drying technique was applied to prepare composite microparticles of a water-insoluble herbicide, atrazine(AT) and a water-soluble herbicide 2,4-dichloro phenoxy acetic acid (2,4-D) for the purpose of improving the water solubility of AT. A homogenous mixture of an ethanol solution of AT and an aqueous 2,4-D solution at different ratios were spray dried using a laboratory scale spray drier. Quantitative elemental analysis suggested that the AT/2,4-D ratio in each composite microparticle was nearly the same as the desired formulation ratio. The resulting samples were characterized by powder x-ray diffractometry (XRD), differential scanning calorimetry (DSC), Fourier transform infra red (FT-IR) and scanning electron microscopy (SEM). It was found that the crystallinity of AT and 2,4-D were maintained in the composite particles. Moreover, the release of AT from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of 2, 4 D. Hence, this study shows that it is possible to prepare AT-2,4-D composite microparticles using a laboratory scale spray drier and that this can improve the ability of AT to dissolve in water.     

Acetaminophen particle design using chitosan and a spray-drying technique

In this study matrices were prepared from particles of poorly water-soluble drugs such as acetaminophen (Act) to determine the drug release rate from these matrix particles. The matrix particles were prepared by incorporating drugs into chitosan powder (Cht, carrier) using a spray-drying method. The formation of composite particles was confirmed by scanning electron microscopic (SEM) analysis. The matrix particles prepared by spray-drying were spherical with a smooth surface. The crystallinity of acetaminophen in the composite particles was evaluated by powder X-ray diffraction and differential scanning calorimetry (DSC). The degree of crystallinity of acetaminophen in the matrix particles decreased with a reduction in the weight ratio of acetaminophen relative to the carrier. These results indicate that a solid dispersion of acetaminophen in chitosan forms matrix particles. The interaction between acetaminophen and chitosan was also investigated by FT-IR analysis. FT-IR spectroscopy of the acetaminophen solid dispersion suggested that the carbonyl group of acetaminophen and the amino group of chitosan formed a hydrogen bond. There were some differences at pH levels of 1.2 and 6.8 in the release of acetaminophen from the physical mixture compared to the matrix particles. At pH 1.2, the release from the matrix particles (Act : Cht=1 : 5) was more sustained than from the physical mixtures. The 70% release time, T70, of acetaminophen from the matrix particles (Act : Cht=1 : 5) increased in pH 1.2 fluid by about 9-fold and in pH 6.8 fluid by about 5-fold compared to crystalline acetaminophen. These results suggest that matrix particles prepared by spray-drying are useful as a sustained release preparation.     

Water-soluble proteins as an excipient for drug administration by inhalation

Microspherical particles of composite drugs based on lysozyme and albumin, which can be used in inhalation administration, were prepared by spray drying. The composition of the complexes was determined using experimental and theoretical methods. The use of the protein matrix makes it possible to increase the dissolution rate of the drug in water. The obtained results can be useful for the development of new drug dosage forms with increased bioavailability.

     

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.     

Magnetic and porous nanospheres from ultrasonic spray pyrolysis

We have used an inexpensive high-frequency ultrasound generator from a household humidifier to create a useful source for ultrasonic spray pyrolysis and produced submicrometer silica particles that are porous on the nanometer scale. By using two heated zones, we first initiate polymerization of organic monomers in the presence of silica colloid, which creates in situ a composite of silica with an organic polymer, followed by a second heating to pyrolyze and remove the polymer. The morphology and surface area of the final porous silica are controlled by varying the silica-to-organic monomer ratio. In a single flow process, ferromagnetic cobalt nanoparticles can be easily encapsulated in the porous silica, and the resulting nanospheres are extremely resistant to air oxidation. Products were characterized by SEM, (S)TEM, EDS, XPS, and SQUID.     

Enhancement of the dissolution rates of poorly water-soluble drugs by water-soluble gelatin

The dissolution behavior of several acidic and basic drugs from kneaded mixtures with water-soluble gelatin have been studied in comparison with that of the drug alone. The results revealed a significant increase of dissolution rate of drugs from kneaded mixtures. The water-soluble gelatin showed little interaction with any of the drugs in solution or in the solid state. Interestingly, the contact angle of the kneaded mixture was remarkably decreased compared with that of the drug powder and was found to be almost the same as that of water-soluble gelatin powder. Thus, the enhanced dissolution rate of the drug caused by water-soluble gelatin was explained by the improvement of wettability of the drug by water.     

Effect of grinding with hydroxypropyl cellulose on the dissolution and particle size of a poorly water-soluble drug.

A new benzofuroquinoline derivative, 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one (KCA-098), shows poor oral absorption due to practical insolubility in water. In this study, a co-grinding technique employing a water-soluble polymer was used for improvement of the dissolution rate of KCA-098. Powder X-ray diffraction patterns and IR spectra of KCA-098 showed the conversion of the drug from a crystal state to an amorphous state by grinding with a polymer such as hydroxypropyl cellulose (HPC-SL) or polyvinylpyrrolidone (PVP K30). The particle size of KCA-098 was remarkably reduced to a submicron size by grinding with HPC-SL. The co-ground mixture with HPC-SL showed a rapid dissolution rate and maintained supersaturation for more than 1 h. On the other hand, the co-ground mixture with PVP K30 showed rapid dissolution and supersaturation for a shorter period. These data suggest that the rapid dissolution rate was obtained by the conversion of the drug particles from a crystal to amorphous state by grinding with water-soluble polymers and that a reduction in particle size to the submicron level led to the maintenance of supersaturation due to good dispersion.     

Preparation and evaluation of solid dispersions of nitrendipine prepared with fine silica particles using the melt-mixing method

Solid dispersions (SD) of nitrendipine (NTD), a poorly water-soluble drug, were prepared using the melt-mixing method with hydrophilic silica particles (Aerosil and Sylysia) with different particle size and specific surface areas as carriers. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that NTD in the SDs treated with the melt-mixing method was dispersed in the amorphous state. FT-IR spectroscopy obtained with the SDs indicated the presence of hydrogen bonding between the secondary amine groups of NTD and silanol groups of silica particles. The dissolution property of NTD in the SDs was remarkably improved regardless of the grade of silica. At the end of the dissolution test (60 min) the concentrations of NTD for the SDs with Aerosil 200 and Sylysia 350 were 8.88 and 10.09 microg/ml, corresponding to 28 and 31 times that of the original NTD crystals, respectively. The specific surface area and the adsorbed water amount of the SDs were also significantly improved. The rapid dissolution rate from the SDs was attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. In the stability test, powder X-ray diffraction pattern indicated that amorphous NTD in the SD with Aerosil 200 was stable for at least 1 month under the humid conditions (40 degrees C/75% RH).     

Use of the co-grinding method to enhance the dissolution behavior of a poorly water-soluble drug: generation of solvent-free drug-polymer solid dispersions

The solid dispersion (SD) technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs. In the present work, SDs of the Ca2+ channel blocker dipfluzine (DF) with polyvinylpyrrolidone K30 (PVP) and poloxamer 188 (PLXM) were prepared by the powder solid co-grinding method under a solvent-free condition. The properties of all SDs and physical mixtures were investigated by X-ray diffraction, Fourier-transform infrared, differential scanning calorimetry, scanning electron microscopy, dissolution test, and particles size determination. Eutectic compounds were produced between the DF and PLXM matrix during the co-grinding process, whereas glass suspension formed in the SDs with PVP carrier. Hydrogen bond formation was not observed between DF and carriers and DF was microcrystalline state in the PVP and PLXM matrices. The solubility of DF in different concentration of carriers at 25, 31, and 37°C was investigated; the values obtained were used to calculate the thermodynamic parameters of interaction between DF and carriers. The Gibbs free energy (ΔrGθ) values were negative, indicating the spontaneous nature of dispersing DF into the carriers. Moreover, entropy is the drive force when DF disperses into the matrix of PVP, while, enthalpy-driven dispersing encounters in the PLXM carrier. All the SDs of DF/carriers showed a considerably higher dissolution rate than pure DF and the corresponding physical mixtures. The cumulative dissolution rate at 10?min of the SD with a 1?:?3 DF/carrier ratio increased 5.1-fold for PVP and 5.5-fold for PLXM.     

Preparation and evaluation of solid dispersion for nitrendipine-carbopol and nitrendipine-HPMCP systems using a twin screw extruder

In the present study, we prepared solid dispersions of the poorly water-soluble drug nitrendipine (NIT) using the twin screw extruder method with high-molecular-weight substances, hydroxypropylmethylcellulosephthalate (HPMCP) and Carbopol (CAR), as carriers. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) evaluation showed that solid dispersions can be formed when NIT-HPMCP and NIT-CAR mixtures are treated with the twin screw extruder method. Fourier Transformation IR Spectroscopy (FT-IR) obtained with NIT-HPMCP and NIT-CAR solid dispersions indicated the presence of hydrogen bonding between the drug and the carriers. NIT-CAR solid dispersions were found to give somewhat higher dissolution than crystalline NIT and physical mixtures, while the dissolution of NIT-HPMCP solid dispersions was markedly decreased compared with the crystalline NIT and physical mixtures. These findings indicated that CAR has a greater ability to improve the dissolution of NIT than HPMCP when a twin screw extruder was employed to prepare the solid dispersions. The twin screw extruder method can be used as a simple and effective method for the preparation of solid dispersions to improve the dissolution properties of poorly water-soluble drugs when choosing proper polymers as carriers.