Physicochemical Characterization and Dissolution Study of Solid Dispersions of Lovastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to‐carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

Physicochemical characterization and dissolution study of solid dispersions of Lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to-carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile Lovastatin compared with tablets containing Lovastatin without PEG or PVP.     

Physicochemical characterization of solid dispersions of carbamazepine formulated by supercritical carbon dioxide and conventional solvent evaporation method

Solid dispersions of carbamazepine (CBZ) were formulated by supercritical fluid processing (SCP) and conventional solvent evaporation in polyethylene glycol (PEG) 8000 with either Gelucire 44/14 or vitamin E TPGS NF (d-alpha-tocopheryl PEG 1000 succinate). Formulations were evaluated by dissolution, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry, and excipient cytotoxicity in Caco-2 cells by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. CBZ release was enhanced from supercritical fluid-treated CBZ and the CBZ/PEG 8000 (1:5), CBZ/PEG 8000/TPGS or Gelucire 44/14 (1:4:1) solid dispersions. The radically altered morphologies of SCP samples seen by scanning electron microscopy suggested polymorphic change that was confirmed by the X-ray diffraction and differential scanning calorimetry. Disappearance of the characteristic CBZ melting peak indicated that CBZ was dissolved inside the carrier system. Polymorphic change of CBZ during SCP led to faster dissolution. Therefore, SCP provides advantages over solid dispersions prepared by conventional processes.     

Effect of particle size on the available surface area of nifedipine from nifedipine-polyethylene glycol 6000 solid dispersions

Solid dispersions containing 5%, 10%, 20%, 30% and 50% of nifedipine were prepared with polyethylene glycol (PEG) 6000 as carrier, respectively, by the fusion method. Drug release from four different size fractions of nifedipine-polyethylene glycol 6000 solid dispersions were examined. The probability parameters of Weibull distribution or log-normal distribution could be obtained from linear regression of the dissolution data. The effects of particle size on the dissolution rate of nifedipine were evaluated in terms of the time course of the available surface area (S(t)). The X-ray diffraction patterns showed that nifedipine was dispersed homogeneously in an amorphous state in the solid dispersions with nifedipine concentration up to 10%. The initial values and faster rate of decrease of S(t) during the dissolution process were markedly enhanced in the solid dispersions with lower contents of nifedipine (5% and 10%) due to the formation of high energy metastable (amorphous) states of the drug and differences in the particle sizes had little effect on the values of the available surface area and the dissolution of the drug. Values of available surface area were particle size dependent for the solid dispersions with higher contents of nifedipine (20%, 30% and 50%) and the rate of decrease of S(t) was enhanced as the particle size reduced.     

In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells

In this study improvement in the bioavailability of carbamazepine (CBZ) prepared as solid dispersions by conventional solvent evaporation and supercritical fluid (SCF) processing methods was assessed, along with the elucidation of the mechanism of improved absorption. Solid dispersions of CBZ in polyethylene glycol (PEG) with either Gelucire 44/14 or vitamin E-TPGS (TPGS) were evaluated by intrinsic dissolution. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of TPGS. Cell viability in presence of various concentrations of amphiphilic carriers was seen. In vivo oral bioavailability was determined in rats. The apparent intrinsic dissolution rates (IDR) of both conventional- and SCF-CBZ/PEG 8000/TPGS solid dispersions were increased by 13- and 10.6-fold, respectively, relative to neat CBZ. CBZ was not a substrate of P-glycoprotein. Higher CBZ permeability was seen in presence of 0.1% TPGS. Cell viability studies showed significant cytotoxicity only at or above 0.1% amphiphilic carrier. Supercritical treated formulation (without amphiphilic carrier) displayed oral bioavailability on par with those conventional solid dispersions augmented with amphiphilic carriers. An in vitro-in vivo correlation was seen between IDR and the AUC of the various CBZ solid dispersions. Bioavailability of CBZ was more a function of dissolution as opposed to membrane effects. Although bioavailability from SCF processed dispersions was better than conventionally processed counterparts (except for one formulation containing Gelucire 44/14), an interaction of processing method and inclusion of an amphiphilic carrier, rather by one factor alone contributed to optimal absorption, thus giving contradictory results for Gelucire 44/14 and TPGS formulations.     

Physicochemical characterisation,drug polymer dissolution and in vitro evaluation of phenacetin and phenylbutazone solid dispersions with polyethylene glycol 8000

Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene glycol (PEG) 8000 (carrier), by melt fusion method. Phenacetin and phenylbutazone displayed an increase in the dissolution rate when formulated as solid dispersions as compared with their physical mixture and drug alone counterparts. Characterisation of the solid dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). DSC studies revealed that drugs were present in the amorphous form within the solid dispersions. FTIR spectra for the solid dispersions of drugs suggested that there was a lack of interaction between PEG 8000 and the drug. However, the physical mixture of phenacetin with PEG 8000 indicated the formation of hydrogen bond between phenacetin and the carrier. Permeability of phenacetin and phenylbutazone was higher for solid dispersions as compared with that of drug alone across Caco‐2 cell monolayers. Permeability studies have shown that both phenacetin and phenylbutazone, and their solid dispersions can be categorised as well‐absorbed compounds. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4281–4294, 2011     

布格呋喃固体分散体的体外研究

布格呋喃(buagafuran,AF-5)是以( )香芹酮为起始原料通过立体选择性合成的沉香呋喃类化合物[1].它具有显著的抗焦虑作用,毒副作用低,市场前景广阔.布格呋喃为油状液体,脂溶性强,不溶于水.用植物油稀释进行小鼠灌胃,抗焦虑活性与空白组比较无统计学意义,不能较好地发挥药效.室温放置易发生降解,化学稳定性差.这些缺     

Improvement of the dissolution kinetics of SR 33557 by means of solid dispersions containing PEG 6000

Solid dispersions of SR 33557 in preparations containing from 30 to 80% w/w polyethylene glycol 6000 (PEG 6000) were prepared by the fusion method. The solubility of the drug substance either alone or in solid dispersions was determined in pH 1.2 and 4.5 media (extraction fluid NFXII, without enzyme). A large increase in the solubility was noted from the 80% w/w PEG preparation. A wettability study performed by measuring the contact angle on tablets of either drug substance or PEG 6000, or solid dispersions, revealed a minimal contact angle for the 80% w/w PEG 6000 solid dispersion (eutectic composition of SR 33557/PEG 6000 phase diagram). Dissolution kinetic analysis performed at pH 1.2 on all solid dispersions, on the physical mixtures containing 70 and 80% w/w PEG 6000, and on SR 33557 alone, showed a maximum release rate (100%) for the solid dispersions containing 70 and 80% w/w PEG 6000. The dissolution rate of the physical mixtures was faster than that of the drug substance alone but remained, however, lower than that of the solid dispersions, at the same composition. It was also observed that the dissolution rate, at pH 1.2 and 4.5, of the 70% w/w PEG 6000 solid dispersion was practically pH independent, which was not the case for the drug substance alone. The latter solid dispersion showed a slowing down of the dissolution kinetics after 3 months storage at 50°C whereas no change in the dissolution rate was observed following storage for 12 months at 25°C.     

Development and optimization of solid dispersion containing pellets of itraconazole prepared by high shear pelletization

This study investigated the solid dispersion containing pellets of itraconazole for enhanced drug dissolution rate. The influence of process parameters used during high shear pelletization on the pellet properties including pellet size and dissolution rate was also studied. Solid dispersions of itraconazole were prepared with Eudragit E100, a hydrophilic polymer, by a simple fusion method followed by powdered and characterized by differential scanning calorimetry and X-ray powder diffraction. Solid dispersions containing pellets were consequently prepared using a lab-scale high shear mixer. In order to improve the product quality, a central composite design was applied to optimize the critical process variables, such as impeller speed and kneading time, and the results were modeled statistically. Itraconazole was presented as an amorphous state in the solid dispersion prepared at a drug to polymer ratio of 1:2. Both studied parameters had great effect on the responses. Powdered solid dispersion and pellets prepared using the optimal parameter settings showed approximately 30- and 70-fold increases in dissolution rate over the pure drug, respectively. Solid dispersion prepared by simple fusion method could be an option for itraconazole solubility enhancement. Pelletization process in high shear mixer can be optimized effectively by central composite design.     

Characterization and stability of solid dispersions based on PEG/polymer blends

Solid dispersions were prepared by a melting method from the water-insoluble model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500) or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in order to combine advantages of the different carrier polymers (recrystallization inhibition, processability and stability). The solid dispersions were characterized by dissolution, powder X-ray diffractometry and microscopy directly after preparation and after storage for 3 and 6 months at 25 °C/0% relative humidity (RH) or 3 months at 40 °C/75% RH. More than 80% drugs were released from all solid dispersions within 20 min. The dissolution rate of carbamazepine decreased in the order of PEG 1500 > PEG 1500/Eudragit > PEG 1500/PVP 30 > PEG 1500/PVPVA > PEG 1500/PVP 12. The dissolution rank order was not directly correlated to the amorphous/crystalline state of the drugs, but rather to the properties of the PEG 1500/polymer compositions. Nifedipine was released in the order of PEG 1500 > PEG 1500/PVPVA > PEG 1500/PVP 30 > PEG 1500/PVP 12 > PEG 1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer dispersions except in pure PEG 1500 solid dispersion. The significant increase in dissolution rate of PEG 1500 solid dispersions was due to the reduced crystallinity of the drug and the excellent solubilisation properties of PEG 1500. After 6 months storage at 25 °C/0% RH, the solid dispersions released both drugs in the order PEG 1500/PVPVA > PEG 1500/PVP 30 > PEG 1500/PVP 12 > PEG 1500/Eudragit > PEG 1500. The stabilized amorphous state of the drug resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or PEG 1500/PVP stored for 3 months at 40 °C/75% RH showed phase separation due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15-hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the dissolution rate and the physical state of the drug was significant.     

Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion-based rofecoxib tablets by the direct compression method. Solid dispersion-based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion-based oral tablets.     

Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2

A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG⁰_tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.     

Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: Investigating the relationship between physicochemical characteristics and dissolution behaviour

Solid dispersions and physical mixtures made up of the poorly water-soluble drug UC 781, a polymer and a surfactant were prepared to contribute to the understanding of the relationship between physicochemical characteristics and dissolution behaviour. In addition, to facilitate downstream processing while still favouring drug dissolution to a maximum extent, formulation conditions were investigated to obtain a free flowing powder which contains a maximum amount of surfactant. Poloxamer 407, a polyethylene-polypropylene glycol block copolymer, was selected as a suitable polymer based on UC 781 supersaturation results. d-Alpha-tocopheryl polyethyleneglycol succinate 1000 (TPGS 1000) was preferred as a surfactant since it increased UC 781 dissolution when formulated in a self-micro emulsifying drug delivery system (SMEDDS), as compared to TPGS 400, TPGS 4000 and TPGS 6000. Based on flow properties, a TPGS 1000/Poloxamer 407 ratio of 80/20 was used to prepare solid dispersions by spray drying. Pure drugs, physical mixtures and solid dispersions were characterized by differential scanning calorimetry and X-ray powder diffraction. Eutectic phase behaviour was obtained in which the relative distribution of the polyethylene glycol folding was dependent on UC 781 concentration. Drug release was markedly increased when formulated as a solid dispersion with Poloxamer 407 and TPGS 1000. Formulation of solid dispersions did however not further improve the drug dissolution rate compared to that of physical mixtures. Nonetheless, variability of dissolution results was considerably reduced upon solid dispersion formulation.     

Enhancement of solubility and permeability of Candesartan cilexetil by using different pharmaceutical interventions

The poor solubility and wettability of Candesartan cilexetil (CAN) leads to poor dissolution and hence, low bioavailability after oral administration. The aim of the present study was to improve the solubility and dissolution rate and hence the permeability of CAN by preparing solid dispersions/inclusion complexes. Solid dispersions were prepared using PEG 6000 [hydrophilic polymer] and Gelucire 50/13 [amphiphilic surfactant] by melt agglomeration (MA) and solvent evaporation (SE) methods in different drug-to-carrier ratios, while inclusion complexes were made with hydroxypropyl-β-cyclodextrin (HP-β-CD) [complexing agent] by grinding and spray drying method. Saturation solubility method was used to evaluate the effect of various carriers on aqueous solubility of CAN. Based on the saturation solubility data, two drug-carrier combinations, PEG 6000 (MA 1:5) and HP-β-CD (1:1 M grinding) were selected as optimized formulations. FTIR, DSC, and XRD studies indicated no interaction of the drug with the carriers and provided valuable insight on the possible reasons for enhanced solubility. Dissolution studies showed an increase in drug dissolution of about 22 fold over the pure drug for PEG 6000 (MA 1:5) and 12 fold for HP-β-CD (1:1 M grinding). Ex-vivo permeability studies revealed that the formulation having the greatest dissolution also had the best absorption through the chick ileum. Capsules containing solid dispersion/ complex exhibited better dissolution profile than the marketed product. Thus, the solid dispersion/inclusion complexation technique can be successfully used for enhancement of solubility and permeability of CAN.     

Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8?kDa, 4?kDa and 6.5?kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug.     

Physicochemical characterization and dissolution of norfloxacin/cyclodextrin inclusion compounds and PEG solid dispersions

Increase in the poor water solubility and dissolution rate of norfloxacin was studied. Two systems were used: solid dispersion with PEG 6000 prepared using the fusion method and inclusion complexes with cyclodextrins (β-cyclodextrin and HP-β-cyclodextrin) obtained by freeze-drying. IR spectrophotometry, X-ray diffractometry, and differential scanning calorimetry showed differences between norfloxacin/cyclodextrin complexes and their corresponding physical mixtures, but not between norfloxacin/PEG 6000 solid dispersions and their corresponding physical mixtures. The solubility and dissolution rate of norfloxacin were significantly increased with PEG solid dispersions and cyclodextrin complexes as well as with norfloxacin-CD physical mixtures. However, enhancement was not statistically different either among various cyclodextrin complexes, or between solid dispersions and cyclodextrin complexes.     

尼群地平固体分散体的研制

为了提高难溶性药物尼群地平的溶出度,制备了其固体分散体,考察其体外溶出度并与原料药作对照,筛选出较佳的处方。     

In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions

The present work extended previous physico-chemical investigations on the effects of solid dispersion on the solubility, the dissolution rate and the pharmacokinetic profile of carbamazepine. Solubility studies showed a linear increase in carbamazepine solubility with the increase of PEG 6000 concentration. There is no marked difference between physical mixtures and solid dispersions for the enhancement of carbamazepine solubility by PEG 6000. Less than 60% of pure carbamazepine was dissolved in 90 min. Physical mixtures (carbamazepine phase III) and solid dispersions (carbamazepine phase II) dissolution rates were higher in comparison of the parent drug. The dissolution of carbamazepine phase III was more pronounced than that evoked by the phase II. The dissolution profiles indicated that the percentage of the drug dissolved was dependent on the proportion of PEG 6000. In solid dispersions there was a remarkable enhancement in the dissolution rates of the drug in the vicinity of the eutectic composition as compared with those of corresponding physical mixtures. Hence, the optimum value for the solid dispersion was 80.5+/-1.7% of carbamazepine having dissolved within the first 10 min compared to 40+/-1% for the corresponding physical mixtures of the same composition. Statistical analysis of pharmacokinetic parameters confirmed that the carbamazepine:PEG 6000 binary systems displayed higher bioavailability of the drug than the pure carbamazepine. The area under the curve (AUC) values highlighted the evidence that only slight differences in the bioavailability of the drug occur between physical mixtures and solid dispersions prepared at the 80:20 and 50:50 drug:carrier compositions. However, the mean normalized plasma concentrations showed that standard error deviations are rather wide intervals for pure drug and physical mixtures in comparison to solid dispersions. One additional interesting point to consider is the disappearance of the multiple peaks on the individual kinetic curves of the 50:50 solid dispersion composition. Furthermore, our investigations have highlighted the interest of solid dispersions prepared at -eutectic composition as our preliminary data show that the plasma concentration (C(5h)) of the drug for the 15:85 dispersed sample containing 150 mg of carbamazepine is not significantly different from that obtained for the 50:50 dispersed sample containing 300 mg of the drug.     

Characteristics of Rofecoxib-Polyethylene Glycol 4000 Solid Dispersions and Tablets Based on Solid Dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion–based rofecoxib tablets by the direct compression method. Solid dispersion–based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion–based oral tablets.     

FTIR spectroscopic imaging of dissolution of a solid dispersion of nifedipine in poly(ethylene glycol)

FTIR imaging was applied to study solid dispersions of a poorly water-soluble drug in poly(ethylene glycol) (PEG) and dissolution in water. It has been shown that initially amorphous nifedipine crystallizes within PEG-8000 for formulations with a drug loading of at least 10 wt%. The formation of a significant amount of crystalline drug within the polymer matrix reduces the rate of dissolution of the drug. This FTIR spectroscopic imaging in the ATR mode provides novel insight into the mechanism of dissolution of nifedipine from solid dispersions in water-soluble polymers, which is valuable in optimization of manufacturing these formulations.