Characterization and Dissolution Properties of Ketoprofen in Binary and Ternary Solid Dispersions with Polyethylene Glycol and Surfactants

The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has been investigated. Physicochemical and morphological properties of the various solid systems were determined by differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction analysis, and scanning electron microscopy. The results from dissolution studies, performed according to the USP 24 basket method, indicated that all ternary dispersed systems were significantly (p < 0.001) more efficacious than the corresponding binary ones, by virtue of the additive wetting and solubilizing effect due to the presence of the surfactant. The relative effectiveness of the incorporated surfactant was in the same order as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the solid dispersion preparation method, coevaporated products always gave better results than the corresponding cofused ones; however, this effect was statistically significant (p < 0.001) only in the initial phase of the dissolution process. The most effective solid dispersion was the 10-80-10 w/w drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary coevaporate) and dissolution of about 100% drug after 30 min (in comparison with > 120 min for the binary coevaporate).     

Characterization of ibuproxam binary and ternary dispersions with hydrophilic carriers

This work investigates the possibility of increasing the dissolution properties of ibuproxam (a poorly water-soluble anti-inflammatory drug) using hydrophilic carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), or urea, alone or in combination. Phase-solubility studies showed that the carrier solubilizing power was in the order PEG>PVP>urea and evidenced a synergistic effect in drug solubility improvement when using carrier combinations. Binary and ternary systems, at 20/80 or 20/40/40 (w/w) drug/carrier(s) ratios, prepared by coevaporation of their ethanolic solutions or by cogrinding physical mixtures in a high-energy vibrational micromill, were characterized by differential scanning calorimetry (DSC), hot stage microscopy (HSM), and scanning electron microscopy (SEM) analyses. The results of dissolution tests (USP paddle method), in terms of Dissolution Efficiency, indicated that ternary systems were up to 35% more effective than the corresponding binary preparations and coevaporated products were up to 45% more efficacious than the corresponding coground ones. The IBUX-PEG-PVP coevaporated was the best product, allowing a more than three-times increase in Dissolution Efficiency with respect to drug alone; moreover, t50% (> 60 min for pure ibuproxam) was < 10 min, and 90% dissolution was achieved after 30 min, whereas only 40% was obtained after 60 min for pure drug. The best performance of this system was attributed to a joined effect of the strong amorphizing power of PVP (as demonstrated by solid state analyses) with the high solubilizing efficacy of PEG (as emerged from phase-solubility studies). The drug dissolution rate from solid dispersions remained practically unchanged after one-year storage at room temperature in closed containers.     

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.     

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.     

New metastable form of glibenclamide prepared by redispersion from ternary solid dispersions containing polyvinylpyrrolidone-K30 and sodium lauryl sulfate

Modification of polymorphic forms of poorly water-soluble drugs is one way to achieve the desirable properties. In this study, glibenclamide (GBM) particles with different polymorphic forms, including a new metastable form, were obtained from redispersion of ternary solid dispersion systems. The ternary solid dispersion systems, consisting of GBM, polyvinylpyrrolidone-K30 (PVP-K30) and sodium lauryl sulfate (SLS), were prepared by solvent evaporation method and subsequently redispersed in deionized water. The precipitated drug particles were then collected at a given time period. The drug particles with different polymorphic forms could be achieved depending on the polymer/surfactant ratio. Amorphous drug nanoparticles could be obtained by using a high polymer/surfactant ratio, whereas two different crystalline forms were obtained from the systems containing low polymer/surfactant ratios. Interestingly, a new metastable form IV of GBM with improved dissolution behavior could be obtained from the system of GBM:PVP-K30:SLS with the weight ratio of 2:2:4. This new polymorphic form IV of GBM was confirmed by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffractometry (PXRD) and solid state ¹³C nuclear magnetic resonance (NMR) spectroscopy. The molecular arrangement of the new polymorphic form IV of GBM was proposed. The GBM particles with polymorphic form IV also showed an improved dissolution behavior. In addition, it was found that the formation of the new polymorphic form IV of GBM by this process was reproducible.     

Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions

This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15?min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500?nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5?µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.     

To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole

The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.     

Enhancement of Dissolution of Ethopropazine Using Solid Dispersions Prepared with Phospholipid and/or Polyethylene Glycol

The purpose of this study was to improve the dissolution properties of a poorly water soluble and bioavailable drug, ethopropazine HCl (ET), by incorporating the drug in three different types of solid dispersion systems. Solid dispersions of ET were prepared using 1:1 (w/w) ratios of (1) phospholipid (1,2 dimyristoyl-sn-glycerophosphocholine) (DMPC), (2) polyethylene glycol 8000 (PEG8000), and (3) a novel combination of both DMPC and PEG8000. Using the solvent method of preparation, ET and DMPC and/or PEG were dissolved in chloroform, and solvent subsequently was evaporated using nitrogen gas. The resulting solid dispersion(s) was passed through a 60-mesh sieve. Characterization of ET/DMPC solid dispersion was performed by differential scanning calorimetry (DSC) and X-ray diffractometry studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH 7.4, 37°C ± 0.5°C) using the USP type II (paddle) dissolution apparatus showed significant increases in the dissolution rate of ET with all the solid dispersions in this study. Specifically, within the first 5 min (D5), solid dispersions containing ET/DMPC (1:1) showed an eightfold increase in dissolution; in combination with DMPC and PEG8000 (1:1), there was an approximately sixfold increase; and a fourfold increase was observed with PEG8000 (1:1). Complete dissolution of all solid dispersions occurred within 60 min (D60) of the run. Storage of the ET/DMPC sample for over 4.5 months revealed a decrease in the dissolution rate when compared to freshly prepared sample. Overall, it was concluded that the dissolution rate of ET significantly improved when dispersed in all the selected carrier systems. However, the solid dispersion of ET/DMPC was observed to be superior to the other combinations used.     

Enhancement of Dissolution of Ethopropazine Using Solid Dispersions Prepared with Phospholipid and/or Polyethylene Glycol

The purpose of this study was to improve the dissolution properties of a poorly water soluble and bioavailable drug, ethopropazine HCl (ET), by incorporating the drug in three different types of solid dispersion systems. Solid dispersions of ET were prepared using 1:1 (w/w) ratios of (1) phospholipid (1,2 dimyristoyl-sn-glycerophosphocholine) (DMPC), (2) polyethylene glycol 8000 (PEG8000), and (3) a novel combination of both DMPC and PEG8000. Using the solvent method of preparation, ET and DMPC and/or PEG were dissolved in chloroform, and solvent subsequently was evaporated using nitrogen gas. The resulting solid dispersion(s) was passed through a 60-mesh sieve. Characterization of ET/DMPC solid dispersion was performed by differential scanning calorimetry (DSC) and X-ray diffractometry studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH 7.4, 37°C ± 0.5°C) using the USP type II (paddle) dissolution apparatus showed significant increases in the dissolution rate of ET with all the solid dispersions in this study. Specifically, within the first 5 min (D5), solid dispersions containing ET/DMPC (1:1) showed an eightfold increase in dissolution; in combination with DMPC and PEG8000 (1:1), there was an approximately sixfold increase; and a fourfold increase was observed with PEG8000 (1:1). Complete dissolution of all solid dispersions occurred within 60 min (D60) of the run. Storage of the ET/DMPC sample for over 4.5 months revealed a decrease in the dissolution rate when compared to freshly prepared sample. Overall, it was concluded that the dissolution rate of ET significantly improved when dispersed in all the selected carrier systems. However, the solid dispersion of ET/DMPC was observed to be superior to the other combinations used.     

Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique

Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 µm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage.     

On-line dissolution determination of Baicalin in solid dispersion based on near infrared spectroscopy and circulation dissolution system

Drug on-line circulation dissolution system with near infrared spectrophotometer for dissolution determination was reported in this paper and subsequently partial least squares (PLS) calibration model was established for concentration prediction of Baicalin in solid dispersion. When the main factor number in PLS calibration model was 6, the correlation coefficients of PLS calibration samples and prediction ones were all 0.9999 and the relative standard deviations were 0.69% and 1.10%, respectively, which showed good robustness and predictability. Combining drug circulation dissolution system with the PLS calibration model, dissolution of Baicalin in raw material drug and solid dispersion were obtained at different times. The results indicated that the dissolution property of Baicalin in solid dispersion (especially at the early time) had been significantly improved. The accumulated dissolution of Baicalin in the solid dispersion at 45 min reached nearly 40%, increasing by 15% compared with raw material drug (about 25%). The aforementioned PLS model associated with drug circulation dissolution system provided a simple, accurate and on-line support for dissolution determination of drug, especially at the early time of rapid dissolution.     

Physicochemical,pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407

This study was conducted primarily to improve the solubility of rebamipide, a poorly water-soluble anti-ulcer drug, using novel ternary solid dispersion (SD) systems and secondly to evaluate the effect of solubility enhancement on its pharmacokinetic (PK) and pharmacodynamic (PD) profile. After dissolving the three components in aqueous medium, ternary SD containing the drug, sodium hydroxide (NaOH) and PVP-VA 64 was achieved by spray drying method, which was used as primary SD. Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co-grinding, physical mixing, melting or spray drying. SD was then characterized by dissolution test, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The spray dried SD of poloxamer 407 together with primary SD displayed highest dissolution rate of the drug of about 70% after 2 h. DSC, PXRD and FT-IR characterized the amorphous state and molecular dispersion of the drug in the SD. PK and PD studies in Sprague–Dawley rats revealed that the bioavailability of the drug using optimal SD was about twofold higher than that of reference product, and the irritation area of stomach was significantly reduced in the ulcer-induced rat model using optimal SD as compared to the reference product.     

Characterization of Poly(Ethylene Oxide) as a Drug Carrier in Hot-Melt Extrusion

ABSTRACT

Poly(ethylene oxide) (PEO) as a drug carrier in hot-melt extrusion was studied by using a model drug, nifedipine, in a twin-screw extruder. Binary mixtures of PEO and nifedipine have been shown to be amenable to hot-melting at a temperature as low as 70°C, well below nifedipine's melting point (172°C). Hot-stage microscopy provided visual evidence that nifedipine can form a miscible dispersion with PEO at 120°C. Complete loss of nifedipine crystallinity when extrudated at and above 120°C with a drug loading of 20% (w/w) was further confirmed by differential scanning calorimetry (DSC) and X-ray diffraction. Cross-sectional imaging of the extrudates using scanning electron microscopy indicated homogeneous drug distribution inside PEO when the processing temperature was above 120°C. Raman spectroscopy confirmed drug-PEO interactions at a molecular level. Cryo-milled extrudates showed significant improvement in dissolution rate compared to either pure nifedipine or the physical mixture of PEO and nifedipine. A state of supersaturation was achieved after 10-minute release in pH 6.8 phosphate buffer. Finally, stability study demonstrated that the solid dispersion system is chemically stable for at least 3 months under the conditions of both 25°C/60% RH and 40°C/75% RH. Overall, PEO appears to be a promising aid/carrier to solublize poorly soluble drugs through the formation of solid dispersion via hot-melt extrusion, thereby improving dissolution and absorption.     

Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion

Poly(ethylene oxide) (PEO) as a drug carrier in hot-melt extrusion was studied by using a model drug, nifedipine, in a twin-screw extruder. Binary mixtures of PEO and nifedipine have been shown to be amenable to hot-melting at a temperature as low as 70°C, well below nifedipine's melting point (172°C). Hot-stage microscopy provided visual evidence that nifedipine can form a miscible dispersion with PEO at 120°C. Complete loss of nifedipine crystallinity when extrudated at and above 120°C with a drug loading of 20% (w/w) was further confirmed by differential scanning calorimetry (DSC) and X-ray diffraction. Cross-sectional imaging of the extrudates using scanning electron microscopy indicated homogeneous drug distribution inside PEO when the processing temperature was above 120°C. Raman spectroscopy confirmed drug-PEO interactions at a molecular level. Cryo-milled extrudates showed significant improvement in dissolution rate compared to either pure nifedipine or the physical mixture of PEO and nifedipine. A state of supersaturation was achieved after 10-minute release in pH 6.8 phosphate buffer. Finally, stability study demonstrated that the solid dispersion system is chemically stable for at least 3 months under the conditions of both 25°C/60% RH and 40°C/75% RH. Overall, PEO appears to be a promising aid/carrier to solublize poorly soluble drugs through the formation of solid dispersion via hot-melt extrusion, thereby improving dissolution and absorption.     

Multicomponent Complexes of Piroxicam with Cyclodextrins and Hydroxypropyl Methylcellulose

The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with β‐cyclodextrin (β‐CD) and dimethyl‐β‐cyclodextrin (DM‐β‐CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, K_s, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug‐CD and drug‐CD‐polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta‐potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.     

Formulation of ternary complexes of glyburide with hydroxypropyl-β-cyclodextrin and other solubilizing agents and their effect on release behavior of glyburide in aqueous and buffered media at different agitation speeds

Glyburide, a sulfonylurea derivative, widely used as hypoglycaemic agent. In the present study, an attempt has been made to investigate the most effective third component which can be used with hydroxylpropyl-β-cyclodextrin (HPβCd) to form a ternary complex with glyburide in order to enhance its dissolution rate, as well as reduce the amount of HPβCd used for formulating the binary complex with glyburide. Moreover, the objective of this study was also to develop a discriminatory dissolution media in order to discriminate the effect of the different solubilizing agents used for formulating the ternary complex system. Sodium lauryl sulphate, Poloxamer-188, Polyvinylpyrrolidone K-30, lactose and l-arginine were used to formulate ternary system along with HPβCd and glyburide. The ternary system formulated with glyburide:HPβCd:l-arginine in a proportion of 1:1:0.5 has shown the fastest dissolution rate when compared to other solubilizing agents. Unbuffered aqueous media with stirring speed 50?rpm has produced the most discriminatory dissolution profiles. The DSC thermograms and the powder X-ray analysis revealed the decrease in crystallinity of the drug. This was an indication of amorphous solid dispersion or molecular encapsulation of the drug into the cyclodextrin cavity.     

Preparation and characterization of coenzyme Q10-Eudragit solid dispersion

A solid dispersion of Coenzyme Q10 and Eudragit L 100-55 was prepared using solvent evaporation method. Solid dispersion, physical mixture, and pure compound were then characterized using differential scanning calorimetry and powder x-ray diffraction. Solubility of CoQ10 in different surfactant media was measured, and a suitable dissolution medium was developed to compare the dissolution patterns of the solid dispersion, physical mixture, and the pure compound. Combining labrasol with different surfactants in dissolution media demonstrated an additive effect on CoQ10 solubility. The solubility of CoQ10 in a 4% Labrasol/2% Cremophor EL solution was 562 microg/ml, which was five times higher than the combined solubility in 5% Labrasol (91 microg/ml) and 5% Cremophor EL (7.8 microg/ml). Moderate change in the crystalline pattern of CoQ10 was observed, which was attributed to solvent displacement rather than the degree of crystallinity change. The dissolution test indicated that the in-vitro release of Coenzyme Q10 from its solid dispersion was much faster than its physical mixture, which in turn was faster than the pure drug. The amount of drug released in 12 hours from solid dispersion, physical mixture, and the pure drug was 100, 26.5 and 12.5% respectively. CoQ10 was photostable throughout the dissolution experiments.     

Multicomponent complexes of piroxicam with cyclodextrins and hydroxypropyl methylcellulose

The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with β-cyclodextrin (β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, K_s, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug-CD and drug-CD-polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta-potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.     

Development of glyburide fast-dissolving tablets based on the combined use of cyclodextrins and polymers

Commercial tablets of glyburide exhibit unsatisfactory dissolution profiles and, consequently, problems of bioinequivalence and poor bioavailability. The aim of this work was to develop glyburide fast-dissolving tablets by exploiting the solubilizing effect of different cyclodextrins (CDs), alone or in combination with hydrophilic polymers. Drug-CD and drug-CD-polymer systems, prepared by different techniques, were characterized by differential scanning calorimetry (DSC), X-ray diffractometry, and Fourier transform infra-red (FT-IR) spectroscopy. Tablets containing binary and ternary systems were prepared by direct compression and evaluated for technological properties and dissolution behavior in comparison with a reference formulation containing the plain drug. A significant improvement of the drug dissolution profile was achieved from tablets containing drug-CD systems (coevaporated products doubled drug dissolution efficiency [DE]), but 100% drug dissolution was never reached. Better results were obtained with ternary systems. In particular, polyvinylpyrrolidone (PVP) emerged as the most effective polymer, and tablets with drug-PVP-hydroxypropyl-betaCD coevaporated products showed the best dissolution profiles, reaching 100% dissolved drug within only 15 min.     

The Release Rate of Indomethacin from Solid Dispersions with Eudragite

Abstract

The coprecipitates were prepared by a solvent technique using Eudragit E as carrier and indomethacin as a model drug.

X-Ray diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the physical state of the studied formulations. Up to 50% of indomethacin can be dispersed in an amorphous state in Eudragit E.

The influence of the pH on the in vitro release of solid dispersions has been evaluated. Because of the good solubility of Eudragit E at pH 1.2 a fast dissolution rate of the drug was observed while a marked delay was noticed at pH 7.5 where the polymer is only permeable to water. At pH 5.8 the kinetics of drug release can be modulated by the drug/polymer ratio. The dissolution rate of the drug can be increased by decreasing its amount in the coevaporate.