Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.     

Enhanced solubility and bioavailability of flurbiprofen by cycloamylose

The effect of cycloamylose on the aqueous solubility of flurbiprofen was investigated. To improve the solubility and bioavailability of flurbiprofen (poor water solubility), a solid dispersion was spray dried with a solution of flurbiprofen and cycloamylose at a weight ratio of 1:1. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with a commercial product. Cycloamylose increased solubility of flurbiprofen approximately 12-fold and dissolution of it by 2-fold. Flurbiprofen was present in an unchanged crystalline state, and cycloamylose was a solubilizing agent for flurbiprofen in this solid dispersion. Furthermore, the dispersion gave higher AUC and C_max values compared with the commercial product, indicating that it improved the oral bioavailability of flurbiprofen in rats. Thus, the solid dispersion may be useful to deliver flurbiprofen with enhanced bioavailability without changes in crystalline structure.     

Preparation of high solubilizable microemulsion of naproxen and its solubilization mechanism

With the aim of developing a novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes, various valsartan-loaded solid dispersions were prepared with water, hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulphate (SLS). Effects of the weight ratios of SLS/HPMC and carrier/drug on both the aqueous solubility of valsartan and the drug-release profiles of solid dispersions were investigated. The physicochemical properties of solid dispersions were characterized using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The bioavailability of the solid dispersions in rats was evaluated compared to valsartan powder and a commercial product (Diovan). Unlike the conventional solid dispersion system, the valsartan-loaded solid dispersion had a relatively rough surface and did not change the crystalline form of the drug. It was suggested that the solid dispersions were formed by attaching hydrophilic carriers to the surface of the drug, thus changing from a hydrophobic to a hydrophilic form without changing the crystalline form. The drug-loaded solid dispersion composed of valsartan/HPMC/SLS at a weight ratio of 3/1.5/0.75 improved the drug solubility by about 43-fold. It gave a higher AUC, C(max) and shorter T(max) compared to valsartan powder and the commercial product. The solid dispersion improved the bioavailability of the drug in rats by about 2.2 and 1.7-fold in comparison with valsartan powder and the commercial product, respectively. Thus, the valsartan-loaded solid dispersion would be useful for delivering poorly water-soluble valsartan with enhanced bioavailability and no crystalline changes.     

Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change

To develop a novel flurbiprofen-loaded solid dispersion without crystalline change, various flurbiprofen-loaded solid dispersions were prepared with water, sodium carboxylmethyl cellulose (Na-CMC), and Tween 80. The effect of Na-CMC and Tween 80 on aqueous solubility of flurbiprofen was investigated. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared to commercial product. Unlike conventional solid dispersion systems, the flurbiprofen-loaded solid dispersion gave a relatively rough surface and changed no crystalline form of drug. These solid dispersions were formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in changing the hydrophobic drug to hydrophilic form. Furthermore, the flurbiprofen-loaded solid dispersion at the weight ratio of flurbiprofen/Na-CMC/Tween 80 of 6/2.5/0.5 improved ～ 60-fold drug solubility. It gave higher AUC, T_max, and C_max compared to commercial product. The solid dispersion improved almost 1.5-fold bioavailability of drug compared to commercial product in rats. Thus, the flurbiprofen-loaded solid dispersion would be useful to deliver poorly water-soluble flurbiprofen with enhanced bioavailability without crystalline change.     

A novel solid dispersion system for natural product-loaded medicine: silymarin-loaded solid dispersion with enhanced oral bioavailability and hepatoprotective activity

Abstract

A surface-attached silymarin-loaded solid dispersion with improved dissolution profile and enhanced oral bioavailability was formulated using silymarin, polyvinylpyrrolidone (PVP) and Tween 80 in water. In this solid dispersion, hydrophilic PVP was adhered onto the surface of crystalline drug rendering silymarin hydrophilic without changing its crystallinity. The drug solubility from the optimised solid dispersion prepared with silymarin/PVP/Tween 80 at the weight ratio of 5/2.5/2.5 increased by almost 650-fold compared to drug powder. The drug was physically and chemically stable in the solid dispersion for at least 6 months. Moreover, the solid dispersion enhanced the oral bioavailability of the drug in rats by almost 3-fold compared to the commercial product. The silymarin-loaded solid dispersion also exhibited advanced hepatoprotective bioactivity against CCl₄-induced liver damage compared to silymarin or the commercial product. Thus, this silymarin-loaded solid dispersion would be useful for the enhancement of oral bioavailability and hepatoprotective activity of poorly water-soluble silymarin.     

Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability

To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 μg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C_max and T_max compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.     

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate

To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.     

Development of raloxifene-solid dispersion with improved oral bioavailability via spray-drying technique

The purpose of this study was to develop a raloxifene-loaded solid dispersion with enhanced dissolution rate and bioavailability via spray-drying technique. Solid dispersions of raloxifene (RXF) were prepared with PVP K30 at weight ratios of 1:4, 1:6 and 1:8 using a spray-drying method, and characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, and solubility and dissolution tests. The bioavailability of the solid dispersion in rats was also evaluated compared to those of RXF powder and commercial product. Results showed that the RXF-loaded solid dispersion was in amorphous form with increased solubility and dissolution rate. The absorption of RXF from solid dispersion resulted in approximately 2.6-fold enhanced bioavailability compared to pure drug. Moreover, RXF-loaded solid dispersion gave similar AUC, C_max and T_max values to the commercial product, suggesting that it was bioequivalent to the commercial product in rats. These findings suggest that an amorphous solid dispersion of RXF could be a viable option for enhancing the oral bioavailability of RXF.     

Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray-drying technique

A poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray-drying technique. To develop a novel ibuprofen-loaded gelatin microcapsule with bioavailability enhancement, the effect of spray-drying conditions, gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol encapsulated in gelatin microcapsule were investigated. The ibuprofen solubility and amount of encapsulated ethanol increased as inlet temperature and amount of sodium lauryl sulfate increased, reached maximum at 105 degrees C and 0.6%, respectively and after that followed a rapid decrease. Furthermore, they abruptly increased as the amount of gelatin increased, reaching maximum at 4% then remaining almost stable, but the encapsulated ethanol content decreased noticeably. Likewise, the ibuprofen solubility increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility. However, the encapsulated ethanol content hardly changed irrespective of the amount of ibuprofen. Furthermore, the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 showed ibuprofen solubility of about 290microg/ml and ethanol content of about 160microg/mg. This gelatin microcapsule dramatically increased the initial dissolution rate of ibuprofen compared to ibuprofen powder in pH 1.2 simulated gastric fluid. Moreover, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen in rats than did ibuprofen powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. Our results suggested that the enhanced oral bioavailability of ibuprofen in the gelatin microcapsule was contributed by the marked increase in the absorption rate of ibuprofen due to the crystallinity change to amorphous form and increase in dissolution rate of ibuprofen in the gelatin microcapsule in rats. Thus, the ibuprofen-loaded gelatin microcapsule developed using spray-drying technique with gelatin would be useful to deliver ibuprofen in a pattern that allows fast absorption in the initial phase, leading to better absorption.     

Revaprazan-loaded surface-modified solid dispersion: physicochemical characterization and in vivo evaluation

The purpose of this research was to develop a novel revaprazan-loaded surface-modified solid dispersion (SMSD) with improved drug solubility and oral bioavailability. The impact of carriers on aqueous solubility of revaprazan was investigated. HPMC and Cremophor A25 were selected as an appropriate polymer and surfactant, respectively, due to their high drug solubility. Numerous SMSDs were prepared with various concentrations of carriers, using distilled water, and the drug solubility of each was assessed. Moreover, the physicochemical properties, dissolution and pharmacokinetics of selected SMSD in rats were assessed in comparison to revaprazan powder. Of the SMSDs assessed, the SMSD composed of revaprazan/HPMC/Cremophor A25 at the weight ratio of 1:0.28:1.12 had the most enhanced drug solubility (～6000-fold). It was characterized by particles with a relatively rough surface, suggesting that the carriers were attached onto the surface of the unchanged crystalline revaprazan powder. It had a significantly higher dissolution rate, AUC and C_max, and a faster T_max value in comparison to revaprazan powder, with a 5.3-fold improvement in oral bioavailability of revaprazan. Therefore, from an environmental perspective, this SMSD system prepared with water, and without organic solvents, should be recommended as a revaprazan-loaded oral pharmaceutical alternative.     

Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability

Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12%) and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.     

New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs

The purpose of this study was to develop a novel clopidogrel napadisilate-loaded solid dispersion with improved stability and bioequivalence to the clopidogrel bisulphate-loaded commercial product. Clopidogrel napadisilate prepared in this study appeared as a white crystalline powder unlike clopidogrel base. However, this salt did not improve the solubility of clopidogrel, even with improved stability compared to clopidogrel bisulphate. To improve the solubility of clopidogrel napadisilate, a novel clopidogrel napadisilate-loaded solid dispersion was prepared by the spray-drying technique using HPMC and colloidal silica, and the physicochemical properties, dissolution and bioavailability in beagle dogs were evaluated compared to the clopidogrel bisulphate-loaded commercial product. The solid dispersion composed of clopidogrel napadisilate, HPMC and colloidal silica at a weight ratio of 11.069/3/3.5 improved solubility by 6.5-fold compared to clopidogrel napadisilate, even if it did not improve drug solubility compared to clopidogrel bisulphate. However, unlike clopidogrel bisulphate, this formulation improved the stability of clopidogrel. Furthermore, the clopidogrel napadisilate solid dispersion-loaded tablet showed similar dissolution to the clopidogrel bisulphate-loaded commercial product and was bioequivalent to the commercial product in beagle dogs. Thus, this clopidogrel napadisilate-loaded solid dispersion could be a promising candidate for improving the stability and bioavailability of clopidogrel.     

Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.     

Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability

Objectives Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Methods Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. Key findings SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Conclusions Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non‐absorbable base form.     

Preparation and physicochemical characterizations of tanshinone IIA solid dispersion

This investigation describes a novel approach to prepare solid dispersions of tanshinone IIA using a laboratory-scale planetary ball mill. Poloxamer 188 was employed as the surfactant carrier to improve the solubility and dissolution of the poorly soluble drug, tanshinone IIA. Solubility and dissolution were evaluated compared to the corresponding physical mixtures and pure drug. Furthermore, the physicochemical properties of the solid dispersions were investigated using scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and ultraviolet spectrophotometry. The solid dispersion significantly enhanced drug solubility and dissolution compared with pure drug and the physical mixtures. Scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy analyses of tanshinone IIA/poloxamer 188 system confirmed that there were intermolecular interactions between tanshinone IIA and poloxamer 188 and no conversion to crystalline material. Tanshinone IIA existed in a microcrystalline form in the system. These results suggested that improvement of the dissolution rate could be correlated to the formation of a eutectic mixture between the drug and the carrier. After 60 days the solid dispersion samples were chemically and physically stable. The present studies indicated that the planetary ball mill technique could be considered as a novel and efficient method to prepare solid dispersion formulations.     

卡维地洛-PVPVA64固体分散体的制备与表征

目地：制备卡维地洛的固体分散体,提高其在水中的溶解度和溶出度。方法：以乙烯基吡咯烷酮／醋酸乙烯共聚物（PVPVA64）为载体,无水乙醇为溶剂,制备卡维地洛固体分散体,并通过差示扫描量热法、x-射线粉末衍射法、红外分光光度法、原子力显微镜扫描、溶解度测定、溶出度实验及稳定性试验对固体分散体进行表征。结果：差示扫描量热法、x-射线粉末衍射法以及原子力显微镜扫描的谱图和图像分析表明卡维地洛以无定形状态存在于制得的固体分散体中,而傅里叶变换红外光谱分析则表明在固体分散体中卡维地洛与PVPVA64间可能以氢键结合形式存在。与卡维地洛原料药相比,该固体分散体的溶解度提高了80倍,且1h溶出百分率也从10％以下提高到95．5％。经差示扫描量热法、x-射线粉末衍射法及溶出度实验考察发现,在温度为40℃、相对湿度为75％的环境条件下,于90d内,该固体分散体稳定性良好。结论：卡维地洛与PVPVA64形成固体分散体后可显著提高其溶解度和溶出度,且热力学稳定,可进一步用于制备生物利用度更高的口服固体剂型。     

Preparation, characterization and in vitro dissolution studies of solid dispersion of meloxicam with PEG 6000

The poor solubility and wettability of meloxicam leads to poor dissolution and hence showing variations in bioavailability. The present study is aimed to increase solubility and dissolution of the drug using solid dispersion techniques. The solid binary systems were prepared at various drug concentrations (5-40%) with polyethylene glycol 6000 by different techniques (physical mixing, solvent evaporation). The formulations were characterized by solubility studies, differential scanning calorimetry, fourier transform infrared spectroscopy and in vitro dissolution rate studies. The solubility of drug increased linearly with increase in polymer concentration showing A(L) type solubility diagrams. Infrared spectroscopy studies indicated the possibility of hydrogen bonding with polymer. The differential scanning calorimetry and powder X ray diffraction demonstrated the presence of polymer as eutectica or monotectica in solid dispersion along with the physical characteristics of the drug (crystalline, amorphous or a mixture of both). The solid dispersions of the drug demonstrated higher drug dissolution rates than physical mixtures and pure meloxicam, as a result of increased wettability and dispersibility of drug in a solid dispersion system.     

Preparation, Characterization, and In Vitro Evaluation of Ezetimibe Binary Solid Dispersions with Poloxamer 407 and PVP K30

Ezetimibe (EZE), a water insoluble drug, depicts variable bioavailability. The objective of the present investigation was to improve dissolution characteristics of EZE, which might offer improved bioavailability. The solid dispersions were prepared using poloxamer 407 (L 127) and polyvinyl pyrrolidone by melt and solvent method, respectively. Phase solubility studies indicated linear relationship between drug solubility and carrier concentration. In vitro release studies revealed improvement in the dissolution characteristics of EZE in solid dispersions. Solid dispersion with L 127 gave better rate and extent of dissolution. The best fit model indicating the probable mechanism of drug release from solid dispersions was found to be Korsemeyer–Peppas. The results of characterization of solid dispersions by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction revealed reduction in drug crystallinity which might be responsible for improved dissolution properties. The tablets of solid dispersion, containing L 127 prepared by direct compression, exhibited better drug release as compared to marketed formulation.     

Ibuprofen-loaded ethylcellulose microspheres: analysis of the matrix structure by thermal analysis.

The determination of the drug dispersion state in microspheres prepared by the solvent evaporation method is essential to foresee the stability of the particles and the drug release behavior. The present work deals with ibuprofen-loaded ethylcellulose microspheres, that are characterized by a lower drug melting point than the polymer glass transition temperature. Although annealing experiments were not possible, the study has evidenced the presence of a metastable molecular dispersion for intermediate loadings, coexisting with a solid solution and a crystalline dispersion of the drug in the polymer matrix. In addition, differential scanning calorimetry helped to distinguish between surface and inner ibuprofen crystals, which interact differently with the polymer matrix and therefore have different melting points.     

In sight into tadalafil - block copolymer binary solid dispersion: Mechanistic investigation of dissolution enhancement

Tadalafil is a phosphodiesterase-5 inhibitor that is characterized by low solubility and high permeability. Solid dispersion approach represents a promising carrier system for effective enhancement of dissolution and oral bioavailability of poorly soluble drugs. In the present work, novel tadalafil-loaded solid dispersions employing various block copolymers (Pluronics(?)) were prepared through fusion technique. Their solubility and dissolution properties were compared to the drug alone. In order to elucidate the mechanism of dissolution enhancement, solid state characteristics were investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Furthermore, contact angle measurements were carried out. The sign and magnitude of the thermodynamic parameters indicated spontaneity of solubilization process. The phase solubility studies revealed A(L) type of curves for the carriers. Unlike traditional solid dispersion systems, the crystal form of drug in the formulated systems could not be converted to amorphous form. Most of the studied grades showed dissolution improvement vis-à-vis pure drug, with Pluronic F-127 as the most promising carrier. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model. Thus, the results demonstrated that tadalafil/Pluronic F-127 solid dispersion system is a direct and feasible technology which represents a potential candidate for delivering a poorly water-soluble drug with enhanced solubility and dissolution.