Physicochemical Properties Of Solid Dispersions Research Articles

Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen

Solid dispersions are typically binary systems with a hydrophilic matrix polymer and a lipophilic active substance. During formulation, the drug undergoes a crystalline to amorphous phase transition, which leads to a supersaturated solution providing enhanced bioavailability. The interaction of the active substance and the polymer is unique and influences the level of supersaturation. We aimed to investigate the relationship between low molecular weight polyethylene glycol derivates PEG 1000, 1500, and 2000 and ketoprofen regarding the effect of molecular weight. The physicochemical properties of solid dispersions prepared with hot melt homogenization and their respective physical mixtures were investigated with Fourier transform infrared spectroscopy, powder X-ray diffraction and scanning electron microscopy techniques. A phase solubility study was carried out in hydrochloric acid media which showed no difference between the three polymers, but the dissolution curves differed considerably. PEG 1000 had higher percentage of released drug than PEG 1500 and 2000, which had similar results. These results indicate that when multiple low molecular weight PEGs are suitable as matrix polymers of solid dispersions, the molecular weight has only limited impact on physicochemical characteristics and interactions and further investigation is needed to select the most applicable candidate.

Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: A case study with ketoprofen

Hydrophilic semicrystalline carriers represent an alternative to amorphous polymers due to their low melting temperature, useful for the production of solid dispersions (SDs) by melting-based technologies. This research aims to compare SDs of ketoprofen (KET) and three different semicrystalline carriers (PEG, Poloxamer and Gelucire) regarding miscibility, phase behavior, molecular interactions and stability. KET was chosen owing to its low solubility and high glass forming ability. Estimation of drug-excipient miscibility was performed by Flory-Huggins theory. Negative Gibbs free energy indicated a spontaneous mixing of KET with the three carriers and miscibility in the order PEG > Poloxamer > Gelucire. SDs up to 40 % w/w of drug were produced by melting process at a temperature below KET melting point. Characterization of SDs was performed by differential scanning calorimetry, polarized light microscopy and powder X-ray diffraction. In case of PEG and Poloxamer, the drug incorporation did not affect carrier crystallinity, while KET was in the amorphous state. Differently, KET retarded the crystallization of Gelucire and at high drug loadings the SDs were amorphous and semisolid. FT-IR analysis revealed a strong interaction between KET and the three carriers. Finally, PEG-based SDs above 20 % KET loading displayed drug crystallization after 6 months of storage; while Poloxamer and Gelucire-based SDs showed KET crystallization only at 40 % KET. Due to its less hydrophilic character and limited water uptake, Gelucire showed the best stability among the three excipients.

Recent studies on the processes and formulation impacts in the development of solid dispersions by hot-melt extrusion

Industrial-scale pharmaceutical applications still face many challenges in overcoming the low absorption and bioavailability of poorly water-soluble drugs. Hot-melt extrusion has emerged as a promising approach with continuous processing on an industrial scale for the preparation of drug delivery systems. Many reviews have mentioned the potential applications, processes, principles and advantages and disadvantages of hot-melt extrusion in the pharmaceutical industry. However, a focus on the recent progress of hot-melt extrusion, which investigates the impacts of processes and formulations of solid dispersions of poorly water-soluble drugs, is missing. In this review, various factors, including polymers, drug properties, additives and surfactants, in solid dispersion SD formulations by hot-melt extrusion will be discussed. Moreover, the effects of the hot-melt extrusion process on the physicochemical properties of solid dispersions will be mentioned. The utilization of molecular interactions in hot-melt extrusion to improve drug stability will also be described. Overall, this summary of recent studies on solid dispersion by hot-melt extrusion will provide perspectives and effectiveness for the development of formulations containing poorly water-soluble drugs.

Enhancement of the solubility and the dissolution rate of oral nimodipine formulation with solid dispersion

The present study was an attempt to enhance the dissolution rate of nimodipine (a poorly water-soluble drug), The objective of this study was to evaluate poloxamer 407 as a carrier for nimodipine solid dispersions. The solid dispersions of nimodipine with poloxamer 407 were prepared by the hot melting technique, the molar ratio (3:1). The physicochemical properties of Solid dispersion were investigated by Differential Scanning Calorimetry (DSC), powder x-ray diffraction (PXRD), and Fourier Transform Infrared (FT-IR) spectroscopy. The FT-IR spectra indicated there was no chemical interaction between nimodipine and poloxamer 407 in the solid dispersion. DSC analysis indicated a decrease in the melting point of nimodipine and poloxamer 407 in solid dispersion. The tablet form was prepared by wet granulation of nimodipine with a binder solution of poloxamer 407 and compressed the dried granules of nimodipine into non-friable, stable tablets. The other objective, the performance of two classes of super disintegrates as croscarmellose sodium (Ac-Di-Sol), and polyvinyl pyrrolidone K30 in the dissolution of nimodipine immediate release and promoting disintegration tablets was evaluated. The in-vitro dissolution was determined by using United States Pharmacopeia (USP) type II dissolution test apparatus. All the results indicated that enhancement of the dissolution rate of nimodipine has been done successfully and drug release Kinetics indicated that the drug dissolution was a diffusion equation.

Solubility Improvement of Progesterone from Solid Dispersions Prepared by Solvent Evaporation and Co-milling.

The aim of this contribution was to evaluate the impact of processing methods and polymeric carriers on the physicochemical properties of solid dispersions of the poorly soluble drug progesterone (PG). Five polymers: hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP) and silica (SiO2), and two processing methods: solvent evaporation (SE) and mechano-chemical activation by co-milling (BM) were applied. H-bonding was demonstrated by FTIR spectra as clear shifting of drug peaks at 1707 cm−1 (C20 carbonyl) and 1668 cm−1 (C3 carbonyl). Additionally, spectroscopic and thermal analysis revealed the presence of unstable PG II polymorphic form and a second heating DSC cycle, the presence of another polymorph possibly assigned to form III, but their influence on drug solubility was not apparent. Except for PG–MCC, solid dispersions improved drug solubility compared to physical mixtures. For SE dispersions, an inverse relationship was found between drug water solubility and drug–polymer Hansen solubility parameter difference (Δδt), whereas for BM dispersions, the solubility was influenced by both the intermolecular interactions and the polymer Tg. Solubility improvement with SE was demonstrated for all except PG–MCC dispersions, whereas improvement with BM was demonstrated by the PG–HPMC, PG–PVP and PG–HPMCAS dispersions, the last showing impressive increase from 34.21 to 82.13 μg/mL. The extensive H-bonding between PG and HPMCAS was proved by FTIR analysis of the dispersion in the liquid state. In conclusion, although SE improved drug solubility, BM gave more than twice greater improvement. This indicates that directly operating intermolecular forces are more efficient than the solvent mediated.

Evaluation of Solubility Characteristics of a Hybrid Complex of Components of Soy.

The purpose of this study was to evaluate the solubilities and physicochemical properties of solid dispersions of daidzein (DDZ) and genistein (GST) (the major isoflavones in soybeans) in γ-cyclodextrin (γCD). Dispersions were prepared in distilled water using a three-dimensional ball mill (3DGMw). Phase solubility diagrams confirmed that DDZ/γCD and GST/γCD formed AL type inclusion complexes with a molar ratio of 1:1. A new peak due to inclusion complexes was observed in the results of powder X-ray diffraction (3DGMw(DDZ/γCD = 1:1) and 3DGMw(GST/γCD = 1:1)). Dissolution tests using distilled water found that solubilities of 3DGMw(DDZ/γCD = 1:1) and 3DGMw(GST/γCD = 1:1) were approximately 37- and 51-fold higher, respectively, than the solubilities of pure DDZ and GST. These observations are expected to expand the usefulness of cogrinding of DDZ or GST with γCD using a three-dimensional ball mill.

Application of scCO2 technology for preparing CoQ10 solid dispersion and SFC-MS/MS for analyzing in vivo bioavailability

Objective: In this study, solid dispersion (SD) for oral delivery of a poorly water-soluble drug, coenzyme Q10 was developed by supercritical fluid technology and characterized in vitro and in vivo.Methods: Dissolution was used to optimize the formulations of CoQ10-SD. The physicochemical properties of SD were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The supercritical fluid chromatography–electrospray ionization tandem mass spectrometry (SFC–ESI-MS/MS) was used for the in vivo study.Results: The results of DSC and PXRD indicated that the drug in SD was in amorphous state. In vitro drug release, the dissolution of coenzyme Q10 in solid dispersion improved to 78.8% compared with commercial tablets of 0.16%. The area under c–t curve (AUC0–72h) and mean maximum concentrations (Cmax) of CoQ10-SD were 2.43-fold and 3.0-fold, respectively higher than that of commercial tablets in rats, confirming improved bioavailability.Conclusion: Supercritical fluid technology was successfully used for the preparation and analysis of CoQ10-SD for the first time and significantly improved the dissolution and bioavailability of coenzyme Q10.

EFFECT OF SELECTED POLYMERS ON DISSOLUTION AND STABILIZATION OF AMORPHOUS FORM OF MELOXICAM

Objective: Meloxicam is classified as class II corresponding to its high permeability and low solubility (12μg/ml). This study aims to compare the effect of selected polymers on stabilization of amorphous form, and dissolution of meloxicam by preparation of different solid dispersions using selected polymers (chitosan oligomers, polyvinylpyrrolidone K30, and polyethylene glycols).Methods: These solid dispersions were prepared using two different methods; solvent evaporation method for the two molecular weights chitosan carriers (16 and 11KDa) and polyvinylpyrrolidone-K30 and melting method for the two different molecular weights polyethylene glycol (4000 and 6000). The physicochemical properties of solid dispersions were analyzed using differential scanning calorimetry, Fourier transform infra-red analysis, Powder X-ray diffraction, and scanning electron microscopy. Selected dispersions were then compared to two selected marketed drugs (Mobic® and Moven®).Results: Best dissolution rates were obtained for both polyvinylpyrrolidone-K30 and polyethylene glycol 6000, followed by chitosan 16 kDa, chitosan 11 kDa, and polyethylene glycol 4000. Increasing polymeric ratio increased dissolution rate except for chitosan. Precipitation of the drug as amorphous form occurred in chitosan and polyvinylpyrrolidone-K30 dispersions, while no change in crystallinity obtained for polyethylene glycol dispersions. Failure of polyvinylpyrrolidone-K30 in the maintenance of stability during storage time was observed while re-crystallization occurred in chitosan-based dispersions, which ends with preferences to polyethylene glycol dispersions. After comparing the release of selected dispersions with the two selected polymers; all dispersions got a higher release than that of the two marketed drugs release.Conclusion: The dissolution profile of meloxicam has been increased successfully in a reproducible manner.

The use of spray freeze drying for dissolution and oral bioavailability improvement of Azithromycin

Azithromycin is a poorly water-soluble drug with a low bioavailability. The main purpose of this investigation was to increase the solubility and dissolution of Azithromycin by the preparation of its solid dispersions, using the spray freeze drying (SFD) technique. The physicochemical properties of solid dispersions and interactions between the drug-polymer were evaluated using UV–Vis, FT-IR, DSC and PXRD. The surface morphology of the samples was observed by SEM. In order to carry out an assessment of the drug released, the dissolution test was performed. The in vitro drug released profiles were studied and it was found that the dissolution rate of the solid dispersion SFD sample (SFD-SD) was higher than the intact drug. In addition, the saturation solubility of the SFD-SD was significantly higher than the pure drug. The FT-IR spectra showed there was no chemical incompatibility between the drug and polyvinyl alcohol (PVA). The DSC thermograms revealed no possible physical interaction between the drug and the carrier. The surface morphology of samples showed the amorphous state and the distribution of the drug within the carrier particles. The dissolution of the SFD-SD formulation was increased up to 8.9 times more than pure drug utilizing the SFD technique.

Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents

Solid dispersions of nifedipine (NDP), a poorly water-soluble drug, and amino methacrylate copolymer (AMCP) with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate, titanium dioxide, and mesoporous silica from rice husks (SRH), were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC). The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy (SEM). The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium. The results suggested that solid dispersions containing adsorbents (SRH in particular) demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

Effect of γ-cyclodextrin derivative complexation on the physicochemical properties and antimicrobial activity of hinokitiol

The aim of this study was to evaluate the physicochemical properties of solid dispersion on mixtures of hinokitiol (HT) and γ-cyclodextrin (γ-CD) and of HT and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD). Differential scanning calorimetry revealed that coground HT/γ-CD at a molar ratio of 1:1 and HT and HP-γ-CD at molar ratios of 1:1 and 1:2 lacked an endothermic peak due to melting of HT crystals. Powder x-ray diffraction revealed that HT crystal showed a halo pattern respectively, by mixing and grinding of the CDs and HT. Thus, coground HT/γ-CD and HT/HP-γ-CD at a molar ratio of 1:1 had molecular interaction. Assessment of dissolution revealed that ground mixtures had improved dissolution of HT compared to HT crystals, ground HT alone, and physical mixtures containing HT. 1H-1H NOESY NMR suggested that the 7-membered ring and isopropyl group of HT were located within the cavity of γ-CD and HP-γ-CD. The antimicrobial tests indicated that ground mixtures exhibited a minimum inhibitory concentration (MIC) of 20 μg/mL against Bacillus subtilis, 40 μg/mL against Staphylococcus aureus, and 20 μg/mL against Escherichia coli. GMs were found to have 4 times more antimicrobial activity than HT crystals. Ground mixtures also exhibited MIC of 160 μg/mL against Pseudomonas aeruginosa and they were found to 2 times more antimicrobial activity than HT crystals. Improvement in antimicrobial activity with the formation of inclusion complexes is presumably due to increase the solubility of HT as a result of the formation of HT/CD inclusion complexes.

Study on solid dispersion of precipitated calcium carbonate-based oleanolic acid

Oleanolic acid-precipitated calcium carbonate solid dispersion was prepared by using solvent evaporation method. The microscopic structure and physicochemical properties of solid dispersion were analyzed using differential scanning calorimetry and scanning electron microscopy (SEM). And its in vitro release also was investigated. The properties of the precipitated calcium carbonate was studied which was as a carrier of oleanolic acid solid dispersion. Differential scanning calorimetry analysis suggested that oleanolic acid may be present in solid dispersion as amorphous substance. The in vitro release determination results of oleanolic acid-precipitated calcium carbonate (1: 5) solid dispersion showed accumulated dissolution rate of.oleanolic acid was up to 90% at 45 min. Accelerating experiment showed that content and in vitro dissolution of oleanolic acid solid dispersion did not change after storing over 6 months. The results indicated that in vitro dissolution of oleanolic acid was improved greatly by the solid dispersion with precipitated calcium carbonate as a carrier. The solid dispersion is a stabilizing system which has actual applied value.

Release modulation of highly water soluble drug using solid dispersion: impact of dispersion and its compressed unit

In present day, availability of various carriers, innovative techniques of production and plenty of solvents support the growth of solid dispersion (SD) technology in pharmaceutical industries to overcome many issues. The present study was aimed to develop SD based sustained release system of Milnacipran HCl (MH). The SD containing ethyl cellulose, Eudragit RLPO and Eudragit RSPO at drug–polymer ratios of 1:1, 1:2, and 1:3 were developed using solvent evaporation technique and different waxes at ratio of 1:1, 1:1.25, 1:1.5 and 1:1.75 with drug were developed by melting method. The physicochemical properties of SD were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The desired SD batch was further compressed into tablet unit to achieve predetermined once a day drug release. Tablets prepared were evaluated for physicochemical parameters, in vitro drug release, drug release kinetics and scanning electron microscopy. Out of selected carriers, bees wax had shown maximum release retardation. The results of FTIR, DSC and XRD studies exhibited poor interaction amongst MH–bees wax and retention of crystalline state of MH in SD system. The presence of Benecel® (HPMC K 200 M; 75 mg) in tablets comprising SD (1:1.25, MH:bees wax) revealed remarkable drug release extension and it was considered an optimal. The later was submitted to short term stability study and its results indicated the stable characteristic of system. Drug release from optimized formulation fitted well into Higuchi model with anomalous diffusion. The compressed unit of SD system of highly water soluble drug can be successful single day regimen.

Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion

The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion (HME). Carbamazepine (CBZ) was selected as model drug and combinations of Kollidon VA64 (VA64), Soluplus (SOL) and Eudragit EPO (EPO) were utilized as carriers. Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters, differential scanning calorimetry (DSC), hot stage microscopy and thermogravimetric analysis. Physicochemical properties of solid dispersions were determined by DSC, X-ray diffraction, fourier transform infrared spectroscopy, dissolution and accelerated stability testing. The results show that drug-polymer miscibility at temperatures below the melting point (Tm) of CBZ was improved by combining EPO with VA64 or SOL. With 30% drug loading in a solid dispersion in SOL:EPO (1:1, w/w), CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form. The dissolution rate of the solid dispersion was significantly increased (approximately 90% within 5min) compared to either the pure drug (approximately 85% within 60min) or the corresponding physical mixture (approximately 80% within 60min) before and after storage. The solid dispersion in SOL:EPO (1:1, w/w) was relatively stable at 40°C/75% RH under CBZ tablet packaging conditions for at least 3 months. In conclusion, polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.

Solubility and dissolution rate enhancement of lumefantrine using hot melt extrusion technology with physicochemical characterisation

The interest in hot-melt extrusion as a drug delivery technology for the production of solid dispersion is growing rapidly. Lumefantrine (LUMF) is an antimalarial drug that exhibits poor oral bioavailability, in consequence of its poor aqueous solubility. To improve its antimalarial activity, solid dispersion formulation using hot melt extrusion technology was prepared. Appropriate selection of polymers, favoured the production of amorphous LUMF-polymer solid dispersions. The physicochemical properties of solid dispersions were characterized using scanning electron microscope, Infrared spectroscopy, differential scanning calorimetry and X-ray diffraction. LUMF SD showed enhanced dissolution rate attributed to amorphosization of LUMF. The IC50 value of LUMF SD formulations was found to be (0.084–0.213 ng/mL) i.e. 220–101 times lower than the IC50 value of pure LUMF (18.2 ng/mL) and 45–18 times lower than the IC50 value of standard antimalarial drug, chloroquine (3.8 ng/mL). Molecular dynamic simulation approach was used to investigate drug-polymer molecular interaction using computational modelling Schrodinger® software. LUMF SD powder makes the Coartem® therapy more operative with value-added beneficial comeback.

Preparation, characterization, and in vivo evaluation of tanshinone IIA solid dispersions with silica nanoparticles

We prepared solid dispersions (SDs) of tanshinone IIA (TSIIA) with silica nanoparticles, which function as dispersing carriers, using a spray-drying method and evaluated their in vitro dissolution and in vivo performance. The extent of TSIIA dissolution in the silica nanoparticles/TSIIA system (weight ratio, 5:1) was approximately 92% higher than that of the pure drug after 60 minutes. However, increasing the content of silica nanoparticles from 5:1 to 7:1 in this system did not significantly increase the rate or extent of TSIIA dissolution. The physicochemical properties of SDs were investigated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and Fourier transforms infrared spectroscopy. Studying the stability of the SDs of TSIIA revealed that the drug content of the formulation and dissolution behavior was unchanged under the applied storage conditions. In vivo tests showed that SDs of the silica nanoparticles/TSIIA had a significantly larger area under the concentration-time curve, which was 1.27 times more than that of TSIIA (P < 0.01). Additionally, the values of maximum plasma concentration and the time to reach maximum plasma concentration of the SDs were higher than those of TSIIA and the physical mixing system. Based on these results, we conclude that the silica nanoparticle based SDs achieved complete dissolution, increased absorption rate, maintained drug stability, and showed improved oral bioavailability compared to TSIIA alone.

Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose, it was prepared using spray-drying techniques with cycloamylose at a weight ratio of 1:1. The effect of cycloamylose on aqueous solubility of ibuprofen was investigated. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with ibuprofen powder. This ibuprofen-loaded solid dispersion improved about 14-fold drug solubility. Ibuprofen was present in an unchanged crystalline state, and cycloamylose played the simple role of a solubilizing agent in this solid dispersion. Moreover, the dispersion gave 2-fold higher AUC (area under the drug concentration-time curve) value compared with a ibuprofen powder, indicating that it improved the oral bioavailability of ibuprofen in rats. Thus, the solid dispersion may be useful to deliver ibuprofen with enhanced bioavailability without crystalline change.

Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes

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.

이부프로펜과 셀룰로오스아세테이트의 고체분산체 제조방법에 따른 물리화학적 성질 및 용출 특성

고체분산체는 난용성약물의 용해도를 향상시키는 기술로 용출특성은 고분자의 성질, 고분자의 함량 및 물리화학적 성질에 의하여 변화한다. 본 연구에서는 이부프로펜과 셀룰로오스 아세테이트를 사용하여 분무건조와 로터리 증발법을 사용하여 고체분산체를 제조하였다. 제조한 고체분산체의 표면성질을 주사전자현미경(SEM)을 사용하여 분석하였으며, X선 회절기(X-RD)와 시차주사열량계(DSC)를 사용하여 결정성 변화를 관찰하였다. 고체분산체의 화학적 변화를 관찰하기 위하여 적외선 분광기(FTIR) 분석을 하였으며, 수분 친화도를 측정하기 위하여 수분접촉각 측정을 하였다. 용출 특성은 인공장액(pH 6.8) 및 인공위액(pH 1.2)에서 관찰하였다. 실험결과 약물의 결정성은 고분자의 비율이 증가하면 결정성이 감소하였으며, 화학적 변화는 없었다. 수분 친화도는 고분자비율과 비례하였으며, 분무건조로 제조된 고체분산체의 경우가 조금 높은 수분 친화도를 가졌다. 용출실험 결과 인공위액에서는 고분자의 비율이 높아질수록 용출률이 증가하였으며, 인공장액에서의 용출속도는 고분자의 비율과 반비례하는 것을 볼 수 있었다.

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.