Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-proce...Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.展开更多
The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of mol...The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.展开更多
Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluate...Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluated in-silico for their toxicity hazard. Acetol, an impurity likely present in different topical pharmaceutical excipients such as propylene glycol and glycerol, was withheld for the evaluation of its health risk after dermal exposure. 〈br〉 An ex-vivo in-vitro permeation study using human skin in a Franz Diffusion Cell set-up and GC as quantification methodology showed a significant skin penetration with an overall Kp value of 1.82 ？ 10 ？ 3 cm/h. Using these data, limit specifications after application of a dermal pharmaceutical product were estimated. Based on the TTC approach of Cramer class I substances, i.e. 1800 mg/（day？person）, the toxicity-qualified specification limits of acetol in topical excipients were calculated to be 90 mg/mL and 180 mg/mL for propylene glycol and glycerol, respectively.展开更多
Particle sizes play a major role to mediate charge transfer, both between identical and different material surfaces. The study probes into the probable mechanism that actuates opposite polarities between two different...Particle sizes play a major role to mediate charge transfer, both between identical and different material surfaces. The study probes into the probable mechanism that actuates opposite polarities between two different size fractions of the same material by analyzing the charge transfer patterns of two different sizes of microcrystalline cellulose(MCC). Quantum scale calculations confirmed alteration of charge transfer capacities due to variation of moisture content predicted by multiple surface and bulk analytical techniques. Discrete Element Method(DEM) based multi-scale computational models pertinent to predict charge transfer capacities were further implemented, and the results were in accordance to the experimental charge profiles.展开更多
The objective of the current research article is to provide a comprehensive review of excipients impact on the stability of the drug product and their implications during the product development. Recent developments i...The objective of the current research article is to provide a comprehensive review of excipients impact on the stability of the drug product and their implications during the product development. Recent developments in the understanding of the degradation pathways further impact methodologies used in the pharmaceutical industry for potential stability assessment. The formation of drug excipient adducts was very common based on the sensitive chemical moieties in the drugs and the excipients. The formation of the impurities was not limited to drug related impurities but there were several possibilities of the drug-excipient adduct formations as well as excipient impurities reaction with Active Pharmaceutical Ingredients. Identification of drug degradation in presence of excipients/excipient impurities requires extensive knowledge and adequate analytical characterization data. Systematic literature review and understanding about the drug formulation process, give you a smooth platform in establishing the finished product in the drug market. This paper discusses mechanistic basis of known drug-excipient interactions with case studies and provides an overview of common underlying themes in solid, semisolid and parenteral dosage forms.展开更多
Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities gener...Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol,compared to 95.8% in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.展开更多
In order to retain structural and functional integrity, protein medicines are frequently stabilized with excipients in aqueous solutions. The goal of this investigation was to see how stable IL-2 is with excipients th...In order to retain structural and functional integrity, protein medicines are frequently stabilized with excipients in aqueous solutions. The goal of this investigation was to see how stable IL-2 is with excipients that are acceptable for cell therapy. We investigated the time-dependent stability of commercially available recombinant IL-2 in aqueous solutions (CTS, RPMI, PBS, and water) at different temperatures [2°C - 8°C, room temperature (20°C ± 2°C) and 37°C] in the presence of excipients (EDTA, methionine, histidine, and glycine) over a period of up to 30 days. To detect and quantify IL-2, reversed phase high performance liquid chromatography was employed. Electrophoresis on a sodium dodecyl sulfate polyacrylamide gel was used to assess conformational stability. We discovered that IL-2 stability was improved in aqueous solutions including excipients, and that it may have retained its biological activity and sterility in these conditions.展开更多
Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical...Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.展开更多
In this study, the application of sodium bentonite(SB) in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol,...In this study, the application of sodium bentonite(SB) in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed.Compatibility studies were conducted using both Deferential Scanning Calorimeter(DSC)and Fourier Transform Infrared Spectroscopy(FTIR). The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However,metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.展开更多
When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic...When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.展开更多
Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical f...Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.展开更多
A lab-scale adiabatic reactor has been self-made to characterize the coupled properties of heat and reactions during the co-thermal-processing of coal and biomass with steam or steam/O_(2) gasification agents.Results ...A lab-scale adiabatic reactor has been self-made to characterize the coupled properties of heat and reactions during the co-thermal-processing of coal and biomass with steam or steam/O_(2) gasification agents.Results showed that the synergistic effects caused by heat transfer between corncob and coal at different mixing ratios were heavily determined by coal rank and gasification agent.During steam co-processing,the heat transfer from corncob char to adjacent bituminous coal char promoted the water-gas reaction on coal char and contributed to synergistic effects;the heat transfer from anthracite char to adjacent corncob char reduced the kinetic rate of the water-gas reaction on coal char and contributed to inhibitory effects,and the inhibitory effect caused by heat transfer was greater than the promotion effects of biomass mass transfer.The introduction of O_(2) diminished the impact of inter-particle heat transfer and altered the intensity of synergy,decreasing the values of synergy factor of bituminous coal/corncob blends by 17%and increasing the value of synergy factor of anthracite/corncob blends by 142.5%.This study provides sufficient support for the process conditions selection for the production of syngas with specific H_(2)/CO molar ratios and the desired level of gasification performance.展开更多
Chitosan(CS),a natural polymer derived from chitin found in the exoskeletons of crustaceans,has garnered significant interest in the pharmaceutical field due to its unique properties,including biocompatibility and bio...Chitosan(CS),a natural polymer derived from chitin found in the exoskeletons of crustaceans,has garnered significant interest in the pharmaceutical field due to its unique properties,including biocompatibility and biodegradability.In recent years,various studies have reported that CS can affect drug bioavailability,and interestingly,it works as an oral absorption enhancer and inhibitor.This review offers an in-depth analysis of the mechanisms underlying such a phenomenon and supports its application as a pharmaceutical excipient.CS enhances oral drug absorption through various mechanisms,such as interaction with the intestinal mucosa,tight junction modulation,inhibition of efflux transporters,enzyme inhibition,solubility and stability enhancement,and complexation.On the other side,CS exhibits the ability to inhibit the absorption of certain drugs by adsorbing to lipids and sterols,modulating bile acids and gut microbiota,altering drug-cell interaction at the polar interface,and mucus-mediated entrapment and interference.Future potential pharmaceutical research in this field includes elucidating the underneath absorption relevant mechanisms,rational use in formulations as excipient,exploring functional CS derivatives,and developing CS-based drug delivery systems.This comprehensive review highlights CS's versatile and significant role in enhancing and inhibiting oral drug absorption,providing insights into the complexities of drug delivery and the potential of CS to improve therapeutic outcomes.展开更多
目的建立并制定符合《中华人民共和国药典》要求的药用辅料结晶氯化铝的质量标准。方法通过比较国内外结晶氯化铝的质量标准,结合样品系统考察结果,制定性状、鉴别、溶液的澄清度与颜色、硫酸盐、水分、碱金属与碱土金属盐、铁盐等检查...目的建立并制定符合《中华人民共和国药典》要求的药用辅料结晶氯化铝的质量标准。方法通过比较国内外结晶氯化铝的质量标准,结合样品系统考察结果,制定性状、鉴别、溶液的澄清度与颜色、硫酸盐、水分、碱金属与碱土金属盐、铁盐等检查项,新增酸度检查项,建立含量测定方法。结果新增酸度检查项,建议将限度设定为pH 2.5~3.0;方法学考察结果显示,结晶氯化铝质量浓度在5.17~28.95 mg·mL^(-1)范围内线性关系良好(r=0.9999);重复性、稳定性、中间精密度实验的相对标准偏差(relative standard deviation,RSD)均<1.0%;平均加样回收率为99.90%,RSD为1.0%(n=9),成功建立完整的质量控制标准。结论建立的质量标准符合规范,为药用辅料结晶氯化铝的质量标准制定奠定了基础,为该品种的质量控制提供了科学参考。展开更多
文摘Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.
基金National Natural Science Foundation of China(Nos.21921003 and 22201293)the National Key R&D Program of China(No.2023YFC3503400)for financial support。
文摘The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.
基金funded by the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWTVlaanderen) to Jente Boonen (091257)the Special Research Fund (BOF) of Ghent University to Lien Taevernier (01D23812)
文摘Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluated in-silico for their toxicity hazard. Acetol, an impurity likely present in different topical pharmaceutical excipients such as propylene glycol and glycerol, was withheld for the evaluation of its health risk after dermal exposure. 〈br〉 An ex-vivo in-vitro permeation study using human skin in a Franz Diffusion Cell set-up and GC as quantification methodology showed a significant skin penetration with an overall Kp value of 1.82 ？ 10 ？ 3 cm/h. Using these data, limit specifications after application of a dermal pharmaceutical product were estimated. Based on the TTC approach of Cramer class I substances, i.e. 1800 mg/（day？person）, the toxicity-qualified specification limits of acetol in topical excipients were calculated to be 90 mg/mL and 180 mg/mL for propylene glycol and glycerol, respectively.
文摘Particle sizes play a major role to mediate charge transfer, both between identical and different material surfaces. The study probes into the probable mechanism that actuates opposite polarities between two different size fractions of the same material by analyzing the charge transfer patterns of two different sizes of microcrystalline cellulose(MCC). Quantum scale calculations confirmed alteration of charge transfer capacities due to variation of moisture content predicted by multiple surface and bulk analytical techniques. Discrete Element Method(DEM) based multi-scale computational models pertinent to predict charge transfer capacities were further implemented, and the results were in accordance to the experimental charge profiles.
文摘The objective of the current research article is to provide a comprehensive review of excipients impact on the stability of the drug product and their implications during the product development. Recent developments in the understanding of the degradation pathways further impact methodologies used in the pharmaceutical industry for potential stability assessment. The formation of drug excipient adducts was very common based on the sensitive chemical moieties in the drugs and the excipients. The formation of the impurities was not limited to drug related impurities but there were several possibilities of the drug-excipient adduct formations as well as excipient impurities reaction with Active Pharmaceutical Ingredients. Identification of drug degradation in presence of excipients/excipient impurities requires extensive knowledge and adequate analytical characterization data. Systematic literature review and understanding about the drug formulation process, give you a smooth platform in establishing the finished product in the drug market. This paper discusses mechanistic basis of known drug-excipient interactions with case studies and provides an overview of common underlying themes in solid, semisolid and parenteral dosage forms.
基金generously provided by the National Natural Science Foundation of China(Grant No.:81741144)Ministry of Science and Technology of China(Grant No.:2018ZX09J18107-002).
文摘Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol,compared to 95.8% in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.
文摘In order to retain structural and functional integrity, protein medicines are frequently stabilized with excipients in aqueous solutions. The goal of this investigation was to see how stable IL-2 is with excipients that are acceptable for cell therapy. We investigated the time-dependent stability of commercially available recombinant IL-2 in aqueous solutions (CTS, RPMI, PBS, and water) at different temperatures [2°C - 8°C, room temperature (20°C ± 2°C) and 37°C] in the presence of excipients (EDTA, methionine, histidine, and glycine) over a period of up to 30 days. To detect and quantify IL-2, reversed phase high performance liquid chromatography was employed. Electrophoresis on a sodium dodecyl sulfate polyacrylamide gel was used to assess conformational stability. We discovered that IL-2 stability was improved in aqueous solutions including excipients, and that it may have retained its biological activity and sterility in these conditions.
文摘Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.
文摘In this study, the application of sodium bentonite(SB) in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed.Compatibility studies were conducted using both Deferential Scanning Calorimeter(DSC)and Fourier Transform Infrared Spectroscopy(FTIR). The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However,metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.
文摘When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.
文摘Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.
基金supported by the National Key Research and Development Program of China(2022YFE0208400)the Shanxi Province Key Research and Development Program Project(202202090301002).
文摘A lab-scale adiabatic reactor has been self-made to characterize the coupled properties of heat and reactions during the co-thermal-processing of coal and biomass with steam or steam/O_(2) gasification agents.Results showed that the synergistic effects caused by heat transfer between corncob and coal at different mixing ratios were heavily determined by coal rank and gasification agent.During steam co-processing,the heat transfer from corncob char to adjacent bituminous coal char promoted the water-gas reaction on coal char and contributed to synergistic effects;the heat transfer from anthracite char to adjacent corncob char reduced the kinetic rate of the water-gas reaction on coal char and contributed to inhibitory effects,and the inhibitory effect caused by heat transfer was greater than the promotion effects of biomass mass transfer.The introduction of O_(2) diminished the impact of inter-particle heat transfer and altered the intensity of synergy,decreasing the values of synergy factor of bituminous coal/corncob blends by 17%and increasing the value of synergy factor of anthracite/corncob blends by 142.5%.This study provides sufficient support for the process conditions selection for the production of syngas with specific H_(2)/CO molar ratios and the desired level of gasification performance.
基金financially supported by National Key Research and Development Program of China (No.2021YFD1800900)National Natural Science Foundation of China (No.82073790)+2 种基金Special Fund for Youth Team of Southwest University (No.SWUXJLJ202306)Chongqing Science and Technology Commission (Nos.CSTB2022TIAD-LUX0001,CSTB2023NSCQ-JQX0002)Innovation Research 2035 Pilot Plan of Southwest University (No.SWUXDPY22007)。
文摘Chitosan(CS),a natural polymer derived from chitin found in the exoskeletons of crustaceans,has garnered significant interest in the pharmaceutical field due to its unique properties,including biocompatibility and biodegradability.In recent years,various studies have reported that CS can affect drug bioavailability,and interestingly,it works as an oral absorption enhancer and inhibitor.This review offers an in-depth analysis of the mechanisms underlying such a phenomenon and supports its application as a pharmaceutical excipient.CS enhances oral drug absorption through various mechanisms,such as interaction with the intestinal mucosa,tight junction modulation,inhibition of efflux transporters,enzyme inhibition,solubility and stability enhancement,and complexation.On the other side,CS exhibits the ability to inhibit the absorption of certain drugs by adsorbing to lipids and sterols,modulating bile acids and gut microbiota,altering drug-cell interaction at the polar interface,and mucus-mediated entrapment and interference.Future potential pharmaceutical research in this field includes elucidating the underneath absorption relevant mechanisms,rational use in formulations as excipient,exploring functional CS derivatives,and developing CS-based drug delivery systems.This comprehensive review highlights CS's versatile and significant role in enhancing and inhibiting oral drug absorption,providing insights into the complexities of drug delivery and the potential of CS to improve therapeutic outcomes.
文摘目的建立并制定符合《中华人民共和国药典》要求的药用辅料结晶氯化铝的质量标准。方法通过比较国内外结晶氯化铝的质量标准,结合样品系统考察结果,制定性状、鉴别、溶液的澄清度与颜色、硫酸盐、水分、碱金属与碱土金属盐、铁盐等检查项,新增酸度检查项,建立含量测定方法。结果新增酸度检查项,建议将限度设定为pH 2.5~3.0;方法学考察结果显示,结晶氯化铝质量浓度在5.17~28.95 mg·mL^(-1)范围内线性关系良好(r=0.9999);重复性、稳定性、中间精密度实验的相对标准偏差(relative standard deviation,RSD)均<1.0%;平均加样回收率为99.90%,RSD为1.0%(n=9),成功建立完整的质量控制标准。结论建立的质量标准符合规范,为药用辅料结晶氯化铝的质量标准制定奠定了基础,为该品种的质量控制提供了科学参考。
