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.     

A Systematic Approach to Design and Prepare Poly(meth)acrylate Based Solid Dispersions of Poorly Water-soluble Drug by Spray Drying

Objective of present study was to develop formulation which improves solubility of furosemide and stability of spray dried solid dispersion. Various processing parameters were optimized by applying DoE. In first step, screening of poly(meth)acrylates were carried out using solvent casting methods to select appropriate polymer. In second step, solid dispersion was prepared using optimized poly(meth)acrylate via spray drying process and trials were conducted as per DoE. Characterization of spray dried microparticles was carried out using SEM, DSC, XRD, in-vitro dissolution, and stability study. EUDRAGIT® E PO was screened as a suitable polymeric carrier in solvent casting method. In-vitro dissolution showed 100% releases within 20 min for spray dried powder as compared to 9% release for pure drug after 60 min in 0.1 N HCl. SEM analysis revealed conversion of crystalline shape to spherical shape. DSC and XRD confirmed that crystalline form was converted into amorphous form which was stable even after 3 months of storage. Outcome of DoE revealed that, feed rate has significant effect on %LOD while solid content has major effect on the process yield. So, present work indicates that EUDRAGIT® E PO formed a stable spray dried solid dispersion and it has ability to enhance dissolution of furosemide.     

Dissolution enhancement of a poorly water-soluble antimalarial drug by means of a modified multi-fluid nozzle pilot spray drier

A spray drier with a modified multi-fluid nozzle was used to prepare microparticles of a poorly water-soluble antimalarial drug, artemisinin (ART), with the aim of improving its dissolution in water. ART was co-spray dried with a hydrophilic polymer, polyethylene glycol (PEG). The differential scanning calorimetry and X-ray diffraction studies showed that the crystallinity of ART decreased after spray drying. Compared to the physical mixture of ART and PEG, the amorphous phase of ART in the spray dried ART–PEG composites increased, which depended on the weight ratio of drug to polymer. The phase-solubility studies revealed that the aqueous solubility of ART was improved by the presence of PEG. The dissolution of ART from the spray dried ART–PEG composites was more rapid than that from their respective physical mixture and the original ART powder. For example, the dissolution of ART from the spray dried ART–PEG composite (1:6) was 6.5 times higher than that from the original ART powder in the first 30 min. In the mathematical modeling, the Weibull and Korsemeyer–Peppas models were found to best fit to the in vitro dissolution data and then the drug release mechanism was considered as the Fickian diffusion.     

Solid carriers for improved solubility of glipizide in osmotically controlled oral drug delivery system

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli-PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli-PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli-PVP solid dispersion system has suitable solubility behavior in EOP tablets.     

Preparation,characterization and dissolution behavior of artemisinin microparticles

In the present study, a modified 4-fluid nozzle spray drier was used to prepare microparticles of a poorly water soluble drug, artemisinin with the aim of improving its solubility. We also investigated the effect of process variables on the physical properties and dissolution rate of spray dried artemisinin. A full factorial experimentally designed study was performed to investigate the following spray drying variables: inlet temperature and feed concentration. The artemisinin powder and spray dried artemisinin microparticles were characterized by scanning electron microscopy (SEM), differential scanning calorimetric (DSC), X-ray diffraction (XRD) and dissolution. SEM study suggested that the inlet temperature and feed concentration impacted on the particle size of the spray dried particles. The crystallinity of spray dried particles was slightly decreased with increasing inlet temperature and concentration. The dissolution of spray dried particles was markedly improved as compared to commercial artemisinin. A dissolution surface-response model was used to elucidate the significant and direct relationships between drug feed concentration and inlet temperature on one hand and dissolution on the other hand. The best dissolution was found to be 117.00 ± 5.15 μg/mL at the drug feed concentration of 10 g/L and inlet temperature of 140 °C.     

Solid Carriers for Improved Solubility of Glipizide in Osmotically Controlled Oral Drug Delivery System

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli–PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli–PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli–PVP solid dispersion system has suitable solubility behavior in EOP tablets.     

Synchronized release of bufadienolides in a stable Lutrol F127 based solid dispersion prepared with spray congealing

Objective: The objective of this study was to design and prepare a novel solid dispersion using spray congealing to achieve fast and synchronous dissolution of bufalin, cinobufagin, and resibufogenin, three therapeutically complementary drugs.

Methods: The solid dispersion was characterized with dissolution, X-ray diffractometry, and fourier transform infrared spectroscopy after preparation and storage for four?weeks at different temperatures and relative humidity.

Results: It was found that all drugs were molecularly dispersed within matrix and had a significant enhancement (～4-fold higher) of dissolution rate. Furthermore, synchronized release of different drugs from a single carrier was achieved due to the highly molecular dispersibility and the excellent solubilization properties of F127. In addition, the solid dispersion was physically stable for at least four?weeks at controlled conditions. But for samples under stress conditions, the results showed that drug-rich phase was formed and storage temperature was the dominant factor in determining stability of the solid dispersion (SD).

Conclusions: These findings highlight the fitness of spray congealing to co-deliver multiple drugs, which open new perspectives for the development of more advanced combination of multiple therapeutic agents, presumably improving the bioavailability and therapeutic efficacy.     

In vitro and in vivo characterization of fast dissolving tablets containing gliquidone–pluronic solid dispersion

Abstract

The main objective of this study is to increase the dissolution rate of gliquidone using its solid dispersions with pluronic F-68 by solvent evaporation method. The solid dispersion of the drug with pluronic at ratio 1:3 showed the highest dissolution efficiency (50.7%) after 10?min, so it was incorporated in fast dissolving tablets. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to study the interaction between gliquidone and pluronic in the solid state. The FTIR spectroscopic studies revealed no chemical interaction between the drug and pluronic, while the DSC results indicated the amorphous state of gliquidone in the solid dispersion. A 3² full factorial design was used to study the effect of varying concentrations of croscarmellose and sodium starch glycolate as superdisintegrants on the disintegration time and the percentage released after 10?min. The optimized formula showed a disintegration time of 39.1?±?1.2?s and 85.43%?±?5.16% released after 10?min and was selected for the in-vivo studies in rabbits. The selected formula showed significant enhancement of gliquidone bioavailability, about 1.8 times compared with the commercial Glurenor tablets.     

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.     

Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole,a class II compound

Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30?min, while the microparticles prepared by external gelation released 67% within 30?min. It was observed that the AUC and C_max values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.     

Spray drying of drug-swellable dispersant suspensions for preparation of fast-dissolving,high drug-loaded,surfactant-free nanocomposites

Bioavailability of a poorly soluble drug can be improved by preparing a drug nanosuspension and subsequently drying it into nanocomposite microparticles (NCMPs). Unfortunately, drug nanoparticles aggregate during milling and drying, causing incomplete recovery and slow dissolution. The aim of this study is to investigate the impact of various classes of dispersants on drug dissolution from drug NCMPs, with the ultimate goal of enhancing the bioavailability of poorly water-soluble drugs via high drug nanoparticle loaded, surfactant-free NCMPs. Precursor suspensions of griseofulvin (GF, model drug) nanoparticles in the presence of various dispersants were prepared via wet stirred media milling and spray dried to form the NCMPs. Hydroxypropyl cellulose (HPC, polymer) alone and with sodium dodecyl sulfate (SDS, surfactant) was used as a base-line stabilizer/dispersant during milling. Two swellable crosslinked polymers, croscarmellose sodium (CCS) and sodium starch glycolate (SSG), and a conventional soluble matrix former, Mannitol, were used in addition to HPC. Besides being used as-received, CCS was also wet co-milled with GF for two different durations to examine the impact of CCS particle size. Laser diffraction, scanning electron microscopy, powder X-ray diffraction (XRD), UV spectroscopy, NCMP redispersion and dissolution tests were used for characterization. The results show that incorporation of CCS/SSG, preferably wet-milled to a wide particle size distribution, into the spray-dried NCMPs resulted in fast release and dispersion of drug nanoparticle clusters. The swellable dispersants were superior to Mannitol in dissolution enhancement, and could achieve fast release comparable to SDS, demonstrating the feasibility of spray drying to prepare high drug-loaded, surfactant-free nanocomposites.     

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.     

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2³ full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1?h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.     

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.     

Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs – a case study with valsartan

Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30?min against the plain drug which showed only 11.31% of drug release in 30?min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher C_max compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.     

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.     

Part II: Bioavailability in Beagle Dogs of Nimodipine Solid Dispersions Prepared by Hot-Melt Extrusion

ABSTRACT

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_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. 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.     

Lonidamine solid dispersions: in vitro and in vivo evaluation

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 semicrystalline polymers on self-emulsifying solid dispersions of nateglinide: in vitro and in vivo evaluation

This study was undertaken to improve solubility and bioavailability of nateglinide by preparation of stable self-emulsifying solid dispersions (SESDs). The influence of semicrystalline polymers (poloxamer 407, gelucire 50/13) and method of preparation on dissolution behavior, in vivo performance and stability of nateglinide SESDs were investigated. After optimization, SESDs were prepared at 1:5 weight ratio of nateglinide and polymer individually. All the SESDs were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Aqueous solubility of nateglinide was enhanced by 91.82-fold. The SESDs (poloxamer 407-based solid dispersions) achieved rapid and complete drug release (～100% within 45?min) at pH 2. The improved dissolution appeared to be well correlated with the enhanced bioavailability of nateglinide in rabbits. After oral administration of SESDs (poloxamer 407-based solid dispersions), C_max and AUC of nateglinide were increased by ～2.92 and 1.77-folds, respectively, signifying the effectiveness of solid dispersions to improve the bioavailability of nateglinide. Stability during storage was established to show prevention of recrystallization. In conclusion, SESDs with poloxamer 407 in solvent method appeared to be an economic and promising technique to improve the dissolution, bioavailability, and stability of nateglinide.     

Solid dispersions of diflunisal-PVP: polymorphic and amorphous states of the drug

Coprecipitates of diflunisal and polyvinylpyrrolidone (PVP K15, K30, and K90) and physical mixtures were studied using x-ray diffraction analysis, infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and hot-stage microscopy. X-ray diffraction results revealed an almost amorphous state, even in coprecipitates with a high content of drug, next to 70%, which was independent of the polymer molecular weight. The IR spectra of 70:30 drug-PVP solid dispersions suggest the formation of diflunisal-PVP hydrogen bonds. For 70:30 drug-polymer ratio, the physical mixture showed linear dissolution kinetics of free crystals, but the corresponding coprecipitates exhibit two different dissolution processes. When the 25:75 drug-polymer dispersion is analyzed by hot-stage microscopy, only solid plates of PVP are observed; the absence of drug particles may be due to a molecular dispersion of the drug into the polymer. Moreover, polymorphic changes of diflunisal were detected in the solid dispersions in comparison with the corresponding physical mixtures, which are always formed by polymorph II. At high concentrations of drug (75:25 and 80:20), x-ray diffraction patterns of solid dispersions showed the partial recrystallization of the drug, displaying the main diffraction peaks of polymorph I when ethanol was used as coprecipitation solvent, whereas diflunisal form IV was obtained in chloroform.