Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To p...Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.展开更多
Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepato...Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.展开更多
The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitr...The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.展开更多
In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with ...In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via HME.Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable.On the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and Raman spectroscopy.Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC.Atomic Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus,with chemical shift drifting and line broadening.MD simulation studies using computational modelling showed intermolecular interaction between molecules.Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems.Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD.The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.展开更多
Solid dispersion of calcitriol with lipophilic surfactants and triglycerides was developed by melt-mixing method to modify the release and enhance stability of the drug.The solid dispersions were characterized by diff...Solid dispersion of calcitriol with lipophilic surfactants and triglycerides was developed by melt-mixing method to modify the release and enhance stability of the drug.The solid dispersions were characterized by differential scanning calorimetry(DSC),hot stage polarized optical microscopy(HSPM),infrared spectroscopy(FTIR)and stability studies.The solid dispersion significantly enhanced the stability of calcitriol,which could be attributed to the high antioxidant activity of the solid lipid dispersion.The rapid dissolution rate from the solid dispersion was attributed to the amorphous or solid solution state of drug with improved specific surface area and wettability than the drug crystals.Therefore,solid dispersion of calcitriol with D-a-tocopheryl polyethylene glycol 1000 succinate(TPGS)offers a good approach to modify the release and enhance stability of calcitriol.The influence of lipophilic solid dispersion on drug bioavailability needs further investigation.展开更多
Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further...Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further investigation.In this study,solid dispersions of ketoprofen in three hydrophilic carriers,i.e.PVP K30,PVPVA 6:4 and PVA were prepared and characterized.Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API.This result is coinciding to evaluation of drug-polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug-polymer interaction.XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA.Interestingly,dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system.Thus,it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.展开更多
Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal abs...Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].展开更多
Nimodipine(NMD)is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological...Nimodipine(NMD)is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders,such as stroke which is associated with biological rhythm.This study was mainly designed to solve the drawback of conventional NMD solid dosage form,low bioavailability and limited clinical efficacy,by preparing enteric solid dispersion(SD)and the SD was prepared via melting method.The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry(DSC),powder X-ray diffraction(PXRD)and dissolution studies.Compared with pure drug and physical mixture,the dissolution of NMD-SD was enhanced dramatically(about 80%).Furthermore,in consideration of the biological rhythm of stroke,we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method.As shown in the dissolution studies,the tablet released less than 10%in the artificial gastric acid in the initial 2 h and released 32.1%,75%,more than 90%at 4,10 and 14 h respectively in the artificial intestinal fluid.This investigation has solved the problems of oral solid dosage forms of NMD,and it has the good industry prospect.展开更多
The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively...The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.展开更多
[Objectives]To investigate the in vitro transdermal effect of curcumin solid dispersion needles prepared with povidone K 30(PVP K30),polyethylene glycol 6000(PEG 6000)and poloxamer 188(block polyether F68,poloxamer 18...[Objectives]To investigate the in vitro transdermal effect of curcumin solid dispersion needles prepared with povidone K 30(PVP K30),polyethylene glycol 6000(PEG 6000)and poloxamer 188(block polyether F68,poloxamer 188,F68)as carrier matrix,respectively.[Methods]Vertical Franz diffusion cell and HPLC method were used to detect the cumulative penetration and skin retention of the microneedles within 12 h.[Results]Within 12 h,the cumulative penetration of PVP K30 microneedles was as high as 7.098μg/cm2,and the skin retention reached 35.28μg/cm2;PEG 6000 and poloxamer 188 microneedles all showed good transdermal effect;while normal curcumin solid dispersion(control)had no obvious transdermal effect.[Conclusions]The transdermal penetration of curcumin is improved after prepared into solid dispersion microneedles,and among different matrixes,PVP K30 is the best choice.展开更多
[ Objective] The study aimed to determine tebuconazole residue in apples and vegetables using matrix solid phase dispersion-gas chro- matography (MSPD-GC). [ Method] The effects of extraction and determination condi...[ Objective] The study aimed to determine tebuconazole residue in apples and vegetables using matrix solid phase dispersion-gas chro- matography (MSPD-GC). [ Method] The effects of extraction and determination conditions on the detection of tebuconazole left in apples and veg- etables were analyzed, and the optimum extraction conditions were determined. [ Result] The recovery rate of tebucenazole was the highest when the ratio of a sample to florisil dispersant was 1 : 4, and the mixture of hexane and acetone ( 1 : 1 ) with total volume of 8 ml was as the eluant. Under the optimum conditions, the relative standard deviation (RSD) of the method was 4.9% -7.6%, and the detection limit was 0.1 tJg/g, while the re- covery rate of tebuconazole changed from 86.7% to 95. 2% . [ Conclusion] The method was simple, accurate, sensitive and applicable to the de- termination of tebuconazole in aaricultural Droducts.展开更多
A low cost,rapid and sensitive preparation method of silica gel supported ionic liquid(SGSIL)combined with matrix solid phase dispersion(MSPD)followed by high performance liquid chromatography(HPLC)with ultraviolet de...A low cost,rapid and sensitive preparation method of silica gel supported ionic liquid(SGSIL)combined with matrix solid phase dispersion(MSPD)followed by high performance liquid chromatography(HPLC)with ultraviolet detection(UV)is proposed,and it was applied to determine the seven active compounds in Salvia Miltiorrhiza herb.SGSIL and ionic liquid[BMIM]BF4 were used as the adsorbent and the green elution reagent in the MSPD procedure.Several extraction conditions including type of filler and elution solvent,the volume of elution solvent,material liquid ratio were optimized.Under the optimum conditions,the SGSIL-MSPD-HPLC method showed a low limit of detection(LOD,S/N=3)of 0.0122-0.8788μg/mL for standard solution,limit of quantification(LOQ,S/N=10)of 0.0406-2.9292μg/mL for standard solution,wide linear range from 1.56 to 2000μg/mL for all compounds for standard solution,correlation coefficients(r)of more than 0.9990,acceptable reproducibility(relative standard deviations,RSDs<3.54%),and precision of RSDs<3.36%for intra-day,RSDs<3.50%for inter-day.The satisfactory recoveries ranged from 96.4 to 102.5,with RSDs less than 3.45%.The developed SGSIL-MSPD method is easier and more suitable for the determination of the seven active compounds in Salvia Miltiorrhiza herb than the traditional ultrasonic extraction.It was an effective and efficient method for the extraction and quantification of the seven active compounds in traditional Chinese herbal samples.展开更多
Introduction:Griseofulvin is an antifungal drug belonging to Biopharmaceutical Classification System(BCS class II)having low solubility.Objectives:To formulate,evaluate and enhance the dissolution of poorly water solu...Introduction:Griseofulvin is an antifungal drug belonging to Biopharmaceutical Classification System(BCS class II)having low solubility.Objectives:To formulate,evaluate and enhance the dissolution of poorly water soluble drug Griseofulvin by using solid dispersion method.Methods:Six formulations were prepared by solid dispersion method using Polyethylene Glycol(PEG 6000)125 mg,0 mg,62.5 mg,100 mg,25 mg,150 mg and superdisintegrants Crospovidone 0 mg,125 mg,62.5 mg,100 mg,25 mg,150 mg in all batches respectively.Findings:Satisfactory results were obtained from evaluation of physical characteristics of Griseofulvin tablets including:carr’s compressibility index(17.5±0.19%to 11.76±0.67%),Hausner ratio(1.21±0.01 to 1.13±0.02)and post compression parameters including:thickness(5.16±0.02 mm to 4.57±0.19 mm),friability(0.024%to 0.322%),hardness(4±0.28 kg/cm^(2)to 5±0.57 kg/cm^(2)),disintegration time(14-870 seconds).Conclusions:F3 was best formulation among all formulated batches with in-vitro drug release 30.05%in 10 minutes,69.21%in 30 minutes and 97.11%in 45 minutes.This indicated that formulation F3 batch with PEG 6000 of 62.5 mg and crospovidone 62.5 mg showed increased dissolution.展开更多
Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therape...Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.展开更多
Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and he...Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.展开更多
OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as c...OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers.Thermogravimetric analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AESD.Optimal prescriptions were screened via the dissolution degree determination method.Using Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion.Acute toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for toxicity.RESULTS:AE-SD showed that AE existed in the carrier in an amorphous state.Compared with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion.Therefore,it was more suitable as a carrier material for AE-SD.The addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of PVP.The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also optimal.Based on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than AE.The results showed that the drug metabolism in AE-SD was better,and the residence time was shorter.The toxicology study showed that both AE and AE-SD had no toxicity.CONCLUSION:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,as demonstrated by in vitro dissolution experiments.In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo,providing a new concept for the research and development of AE preparations.展开更多
The purpose of this study was to cover the bitter taste of arbidol hydrochloride(ARB)and develop dry suspension with combination of solid dispersion and flavors.Taste masking was successfully done by solid dispersion ...The purpose of this study was to cover the bitter taste of arbidol hydrochloride(ARB)and develop dry suspension with combination of solid dispersion and flavors.Taste masking was successfully done by solid dispersion using octadecanol as the carrier by fusion method.Suspending agents,carriers and other excipients were selected.Differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)were performed to identify the physicochemical interaction between drug and carrier,DSC analysis indicated that ARB was amorphous in the solid dispersion,FTIR spectroscopy showed no interaction between drug and carrier.Taste masking was evaluated on six volunteers with a score of 4.9.The results demonstrated successful taste masking.Water was used to study the in vitro dissolution performance of the three formulations of commercial tablet,capsule and self-made suspension.The self-made suspension showed a lower and slower release,the insoluble carrier octadecanol blocked the drug dissolving from the solid dispersion.It was indicated from the primary stability study,the self-made suspensions were sensitive to high temperature,high humidity and strong light conditions,they should be stored in sealed containers away from heat,light and humidity.展开更多
The existence and propagation of transverse surface waves in piezoelectric coupled solids is investigated, in which perfect bonding between a metal/dielectric substrate and a piezoelectric layer of finite-thickness is...The existence and propagation of transverse surface waves in piezoelectric coupled solids is investigated, in which perfect bonding between a metal/dielectric substrate and a piezoelectric layer of finite-thickness is assumed. Dis- persion equations relating phase velocity to material con- stants for the existence of various modes are obtained in a simple mathematical form for a piezoelectric material of class 6mm. It is discovered and proved by numerical examples in this paper that a novel Bleustein-Gulyaev (B-G) type of transverse surface wave can exist in such piezoelectric cou- pled solid media when the bulk-shear-wave velocity in the substrate is less than that in the piezoelectric layer but greater than the corresponding B-G wave velocity in the same pie- zoelectric material with an electroded surface. Such a wave does not exist in such layered structures in the absence of pie- zoelectricity. The mode shapes for displacement and electric potential in the piezoelectric layer are obtained and discussed theoretically. The study extends the regime of transverse sur- face waves and may lead to potential applications to surface acoustic wave devices.展开更多
Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared...Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.展开更多
A rapid,accurate,and sensitive analytical method,ultrasonication-assisted spraying based fine droplet formationeliquid phase microextractionegas chromatographyemass spectrometry(UA-SFDF-LPME-GCMS),was proposed for the...A rapid,accurate,and sensitive analytical method,ultrasonication-assisted spraying based fine droplet formationeliquid phase microextractionegas chromatographyemass spectrometry(UA-SFDF-LPME-GCMS),was proposed for the determination of trace amounts of hydroxychloroquine sulfate in human serum,urine,and saliva samples.To determine the best extraction strategy,several liquid and solid phase extraction methods were investigated for their efficiencies in isolation and preconcentration of hydroxychloroquine sulfate from biological matrices.The UA-SFDF-LPME method was determined to be the best extraction method as it was operationally simple and provided accurate results.Variables such as the extraction solvent,spraying number,sodium hydroxide concentration and volume,sample volume,mixing method,and mixing period were optimized for the proposed method using the onevariable-at-a-time approach.In addition,Tukey’s method based on a post hoc comparison test was employed to evaluate the significant difference between the parameters inspected.After the optimization studies,the limit of detection(LOD)and limit of quantification(LOQ)were determined to be 0.7 and 2.4 mg/kg,respectively.The sensitivity of the GC-MS system based on the LOD was enhanced approximately 440-fold when the UA-SFDF-LPME method was employed.Spiking experiments were also conducted for the human serum,urine,and saliva samples to determine the applicability and accuracy of the proposed method.Recoveries for the human serum,urine,and saliva samples were found to be in the ranges of 93.9%-101.7%,95.2%-105.0%,and 93.1%-102.3%,respectively.These results were satisfactory and indicated that the hydroxychloroquine sulfate level in the above biological samples could be analyzed using the proposed method.展开更多
基金the National Natural Science Foundation of China(No.81872813,22108313,82273880)Natural Science Foundation of Jiangsu Province(No.BK 20200573,BK 20200576)+1 种基金Fundamental Research Funds for the Central Universities(No 2632022ZD16)the Scientific Research Fund of Hunan Provincial Education Department(No.22B0820).
文摘Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.
文摘Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.
基金supported financially by the Subject Chief Scientist Program(10XD14303900)from Science and Technology Commission of Shanghai Municipalitythe Specialized Research Fund for the Doctoral Program of Higher Education of China(20123107110005).
文摘The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.
基金The author is also thankful to UGC(SAP)for providing the research fellowship and Institute of Chemical Technology,ELITE status(Mumbai,India)for providing all facilities and guidance.The authors are thankful to S.A.I.F.department at Indian Institute of Technology,Mumbai for Raman and 1HeCOSY NMR experimental help and analyses.
文摘In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via HME.Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable.On the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and Raman spectroscopy.Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC.Atomic Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus,with chemical shift drifting and line broadening.MD simulation studies using computational modelling showed intermolecular interaction between molecules.Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems.Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD.The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.
基金The work was supported by the National Natural Science Foundation of China(No 81173002)National Science and Technology Support Program(No 2012BAI35B02)International Science and Technology Cooperation and Exchange Projects(No 2008DFA31080).
文摘Solid dispersion of calcitriol with lipophilic surfactants and triglycerides was developed by melt-mixing method to modify the release and enhance stability of the drug.The solid dispersions were characterized by differential scanning calorimetry(DSC),hot stage polarized optical microscopy(HSPM),infrared spectroscopy(FTIR)and stability studies.The solid dispersion significantly enhanced the stability of calcitriol,which could be attributed to the high antioxidant activity of the solid lipid dispersion.The rapid dissolution rate from the solid dispersion was attributed to the amorphous or solid solution state of drug with improved specific surface area and wettability than the drug crystals.Therefore,solid dispersion of calcitriol with D-a-tocopheryl polyethylene glycol 1000 succinate(TPGS)offers a good approach to modify the release and enhance stability of calcitriol.The influence of lipophilic solid dispersion on drug bioavailability needs further investigation.
基金the financial support received from the short term grant 304/PFARMASI/6313055,Universiti Sains Malaysia in carrying out this work.
文摘Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further investigation.In this study,solid dispersions of ketoprofen in three hydrophilic carriers,i.e.PVP K30,PVPVA 6:4 and PVA were prepared and characterized.Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API.This result is coinciding to evaluation of drug-polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug-polymer interaction.XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA.Interestingly,dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system.Thus,it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.
文摘Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].
基金special construction projects fund which belongs to“Taishan ScholardPharmacy Specially Recruited Experts”.
文摘Nimodipine(NMD)is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders,such as stroke which is associated with biological rhythm.This study was mainly designed to solve the drawback of conventional NMD solid dosage form,low bioavailability and limited clinical efficacy,by preparing enteric solid dispersion(SD)and the SD was prepared via melting method.The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry(DSC),powder X-ray diffraction(PXRD)and dissolution studies.Compared with pure drug and physical mixture,the dissolution of NMD-SD was enhanced dramatically(about 80%).Furthermore,in consideration of the biological rhythm of stroke,we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method.As shown in the dissolution studies,the tablet released less than 10%in the artificial gastric acid in the initial 2 h and released 32.1%,75%,more than 90%at 4,10 and 14 h respectively in the artificial intestinal fluid.This investigation has solved the problems of oral solid dosage forms of NMD,and it has the good industry prospect.
文摘The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.
基金2020 National Undergraduate Training Program for Innovation and Entrepreneurship(202010656041).
文摘[Objectives]To investigate the in vitro transdermal effect of curcumin solid dispersion needles prepared with povidone K 30(PVP K30),polyethylene glycol 6000(PEG 6000)and poloxamer 188(block polyether F68,poloxamer 188,F68)as carrier matrix,respectively.[Methods]Vertical Franz diffusion cell and HPLC method were used to detect the cumulative penetration and skin retention of the microneedles within 12 h.[Results]Within 12 h,the cumulative penetration of PVP K30 microneedles was as high as 7.098μg/cm2,and the skin retention reached 35.28μg/cm2;PEG 6000 and poloxamer 188 microneedles all showed good transdermal effect;while normal curcumin solid dispersion(control)had no obvious transdermal effect.[Conclusions]The transdermal penetration of curcumin is improved after prepared into solid dispersion microneedles,and among different matrixes,PVP K30 is the best choice.
基金Supported by the Practice Innovation Training Program of Undergraduates in Jiangsu Province,China
文摘[ Objective] The study aimed to determine tebuconazole residue in apples and vegetables using matrix solid phase dispersion-gas chro- matography (MSPD-GC). [ Method] The effects of extraction and determination conditions on the detection of tebuconazole left in apples and veg- etables were analyzed, and the optimum extraction conditions were determined. [ Result] The recovery rate of tebucenazole was the highest when the ratio of a sample to florisil dispersant was 1 : 4, and the mixture of hexane and acetone ( 1 : 1 ) with total volume of 8 ml was as the eluant. Under the optimum conditions, the relative standard deviation (RSD) of the method was 4.9% -7.6%, and the detection limit was 0.1 tJg/g, while the re- covery rate of tebuconazole changed from 86.7% to 95. 2% . [ Conclusion] The method was simple, accurate, sensitive and applicable to the de- termination of tebuconazole in aaricultural Droducts.
基金This research was supported by Special Research Fund for Young Doctors of Qiqihar Medical University(QMSI2020B-03,hosted by Wenjing Li).
文摘A low cost,rapid and sensitive preparation method of silica gel supported ionic liquid(SGSIL)combined with matrix solid phase dispersion(MSPD)followed by high performance liquid chromatography(HPLC)with ultraviolet detection(UV)is proposed,and it was applied to determine the seven active compounds in Salvia Miltiorrhiza herb.SGSIL and ionic liquid[BMIM]BF4 were used as the adsorbent and the green elution reagent in the MSPD procedure.Several extraction conditions including type of filler and elution solvent,the volume of elution solvent,material liquid ratio were optimized.Under the optimum conditions,the SGSIL-MSPD-HPLC method showed a low limit of detection(LOD,S/N=3)of 0.0122-0.8788μg/mL for standard solution,limit of quantification(LOQ,S/N=10)of 0.0406-2.9292μg/mL for standard solution,wide linear range from 1.56 to 2000μg/mL for all compounds for standard solution,correlation coefficients(r)of more than 0.9990,acceptable reproducibility(relative standard deviations,RSDs<3.54%),and precision of RSDs<3.36%for intra-day,RSDs<3.50%for inter-day.The satisfactory recoveries ranged from 96.4 to 102.5,with RSDs less than 3.45%.The developed SGSIL-MSPD method is easier and more suitable for the determination of the seven active compounds in Salvia Miltiorrhiza herb than the traditional ultrasonic extraction.It was an effective and efficient method for the extraction and quantification of the seven active compounds in traditional Chinese herbal samples.
基金This research received no specific grant from any funding agency in public,commercial,or not-for-profit sectors.
文摘Introduction:Griseofulvin is an antifungal drug belonging to Biopharmaceutical Classification System(BCS class II)having low solubility.Objectives:To formulate,evaluate and enhance the dissolution of poorly water soluble drug Griseofulvin by using solid dispersion method.Methods:Six formulations were prepared by solid dispersion method using Polyethylene Glycol(PEG 6000)125 mg,0 mg,62.5 mg,100 mg,25 mg,150 mg and superdisintegrants Crospovidone 0 mg,125 mg,62.5 mg,100 mg,25 mg,150 mg in all batches respectively.Findings:Satisfactory results were obtained from evaluation of physical characteristics of Griseofulvin tablets including:carr’s compressibility index(17.5±0.19%to 11.76±0.67%),Hausner ratio(1.21±0.01 to 1.13±0.02)and post compression parameters including:thickness(5.16±0.02 mm to 4.57±0.19 mm),friability(0.024%to 0.322%),hardness(4±0.28 kg/cm^(2)to 5±0.57 kg/cm^(2)),disintegration time(14-870 seconds).Conclusions:F3 was best formulation among all formulated batches with in-vitro drug release 30.05%in 10 minutes,69.21%in 30 minutes and 97.11%in 45 minutes.This indicated that formulation F3 batch with PEG 6000 of 62.5 mg and crospovidone 62.5 mg showed increased dissolution.
文摘Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.
基金supported in part by an Ontario Research Fund-Research Excellence(ORF-RE)grant(Ontario,Canada)in partnership with Patheon by Thermo Fisher Scientific,Natural Sciences and Engineering Research Council(NSERC)of Canada Discovery Grant and Equipment Grants to Xiao Yu Wu,University of Toronto(Canada),Leslie Dan Faculty of Pharmacy Dean's Fund to Jamie Anne Lugtu-Pe,University of Toronto(Canada),Mitacs Accelerate Internship sponsored by Candoo Pharmatech Company Inc.to Xuning Zhang(Canada),NSERC CREATE ContRoL program support to Sako Mirzaie and Hao Han R.Chang(Canada),Ontario Graduate Scholarship(OGS)to Hao Han R.Chang(Canada),and Pharmaceutical Sciences graduate department scholarships to Hao Han R.Chang and Kuan Chen,University of Toronto(Canada).
文摘Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.
文摘OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers.Thermogravimetric analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AESD.Optimal prescriptions were screened via the dissolution degree determination method.Using Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion.Acute toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for toxicity.RESULTS:AE-SD showed that AE existed in the carrier in an amorphous state.Compared with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion.Therefore,it was more suitable as a carrier material for AE-SD.The addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of PVP.The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also optimal.Based on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than AE.The results showed that the drug metabolism in AE-SD was better,and the residence time was shorter.The toxicology study showed that both AE and AE-SD had no toxicity.CONCLUSION:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,as demonstrated by in vitro dissolution experiments.In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo,providing a new concept for the research and development of AE preparations.
文摘The purpose of this study was to cover the bitter taste of arbidol hydrochloride(ARB)and develop dry suspension with combination of solid dispersion and flavors.Taste masking was successfully done by solid dispersion using octadecanol as the carrier by fusion method.Suspending agents,carriers and other excipients were selected.Differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)were performed to identify the physicochemical interaction between drug and carrier,DSC analysis indicated that ARB was amorphous in the solid dispersion,FTIR spectroscopy showed no interaction between drug and carrier.Taste masking was evaluated on six volunteers with a score of 4.9.The results demonstrated successful taste masking.Water was used to study the in vitro dissolution performance of the three formulations of commercial tablet,capsule and self-made suspension.The self-made suspension showed a lower and slower release,the insoluble carrier octadecanol blocked the drug dissolving from the solid dispersion.It was indicated from the primary stability study,the self-made suspensions were sensitive to high temperature,high humidity and strong light conditions,they should be stored in sealed containers away from heat,light and humidity.
基金supported by the National Natural Science Foundation of China(10972171)the Program for New Century Excellent Talents in Universities(NCET-08-0429)
文摘The existence and propagation of transverse surface waves in piezoelectric coupled solids is investigated, in which perfect bonding between a metal/dielectric substrate and a piezoelectric layer of finite-thickness is assumed. Dis- persion equations relating phase velocity to material con- stants for the existence of various modes are obtained in a simple mathematical form for a piezoelectric material of class 6mm. It is discovered and proved by numerical examples in this paper that a novel Bleustein-Gulyaev (B-G) type of transverse surface wave can exist in such piezoelectric cou- pled solid media when the bulk-shear-wave velocity in the substrate is less than that in the piezoelectric layer but greater than the corresponding B-G wave velocity in the same pie- zoelectric material with an electroded surface. Such a wave does not exist in such layered structures in the absence of pie- zoelectricity. The mode shapes for displacement and electric potential in the piezoelectric layer are obtained and discussed theoretically. The study extends the regime of transverse sur- face waves and may lead to potential applications to surface acoustic wave devices.
基金the National Nature Science Foundation of China(No.81173008)from Project for Excellent Talents of Liaoning Province(No.LR20110028)from Program for New Century Excellent Talents in University(No.NCET-12-1015).
文摘Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.
基金supported by the Health Institutes of Turkey(TüSEB)(Project No.2020CV01-8946)。
文摘A rapid,accurate,and sensitive analytical method,ultrasonication-assisted spraying based fine droplet formationeliquid phase microextractionegas chromatographyemass spectrometry(UA-SFDF-LPME-GCMS),was proposed for the determination of trace amounts of hydroxychloroquine sulfate in human serum,urine,and saliva samples.To determine the best extraction strategy,several liquid and solid phase extraction methods were investigated for their efficiencies in isolation and preconcentration of hydroxychloroquine sulfate from biological matrices.The UA-SFDF-LPME method was determined to be the best extraction method as it was operationally simple and provided accurate results.Variables such as the extraction solvent,spraying number,sodium hydroxide concentration and volume,sample volume,mixing method,and mixing period were optimized for the proposed method using the onevariable-at-a-time approach.In addition,Tukey’s method based on a post hoc comparison test was employed to evaluate the significant difference between the parameters inspected.After the optimization studies,the limit of detection(LOD)and limit of quantification(LOQ)were determined to be 0.7 and 2.4 mg/kg,respectively.The sensitivity of the GC-MS system based on the LOD was enhanced approximately 440-fold when the UA-SFDF-LPME method was employed.Spiking experiments were also conducted for the human serum,urine,and saliva samples to determine the applicability and accuracy of the proposed method.Recoveries for the human serum,urine,and saliva samples were found to be in the ranges of 93.9%-101.7%,95.2%-105.0%,and 93.1%-102.3%,respectively.These results were satisfactory and indicated that the hydroxychloroquine sulfate level in the above biological samples could be analyzed using the proposed method.