Extraction unit operation is the first step in traditional Chinese medicine(TCM)product manufacturing,and it is crucial in determining the quality of the produced medicine.However,due to a lack of effective multimodal...Extraction unit operation is the first step in traditional Chinese medicine(TCM)product manufacturing,and it is crucial in determining the quality of the produced medicine.However,due to a lack of effective multimodal monitoring and adjustment strategies,achieving high quality and efficiency remains a challenge.In this work,we proposed an artificial intelligence(AI)-based robot platform for the multi-objective optimization of the extraction process.First,a perception intelligence method for multimodal process monitoring was established to track active ingredient transfer and production changes during the extraction process.Second,a digital twin model was developed to reconstruct the field information,which interacted with real-time monitoring data.Furthermore,the model performed real-time inference to predict future production process states by using the reconstructing information.Finally,according to the predicted process states,the autonomous decision-making robot implemented multi-objective optimization,ensuring efficient process adjustments for global optimization.Experimental and industrial results demonstrated that the platform could effectively infer component transfer dynamics,monitor temperature variations,and identify boiling states,ensuring product quality while reducing energy consumption.This pharmaceutical robot could promote the integration of AI and pharmaceutical engineering,thereby accelerating the iterative development and improvement of China’s pharmaceutical industry.展开更多
Ionic liquid(IL)salts of active pharmaceutical ingredients(API)represent promising formulations for poorly-soluble APIs as they eliminate polymorphism commonly associated with conventional API salts.Being highly visco...Ionic liquid(IL)salts of active pharmaceutical ingredients(API)represent promising formulations for poorly-soluble APIs as they eliminate polymorphism commonly associated with conventional API salts.Being highly viscous liquid,oral dosage formulation of API-ILs is challenging,necessitating immobilization onto particulate carriers,typically by spray-drying.This study developed an alternative oral dosage formulation of API-ILs by incorporating them into soft gelatin-alginate pellets,where the alginate’s role was to improve storage stability of hygroscopic and thermally-sensitive gelatin.Poorly-soluble ibuprofen(IBU)and 1-butyl-3-methylimidazolium(BMIM)was used as the model API-IL.The impacts of alginate inclusion at varying gelatin-to-alginate ratios on quality attributes of IBU-BMIM-loaded pellets were investigated.The evaluated attributes included physical appearance,IBU-BMIM payload,dosage uniformity,flowability,IBU-BMIM release,and IBU solubility enhancement.The results showed IBU-BMIM remained in its liquid-like amorphous form upon incorporation into the pellets,thereby preserving its solubility enhancement capability,albeit at a lower degree due to slower IBU-BMIM release upon alginate inclusion.Alginate inclusion also influenced the pellets’physical appearance,thickness,flowability,and gelatin’s secondary structures,while having minimal impacts on payload and dosage uniformity.Importantly,the pellets remained stable after one-month of accelerated storage(40℃ and 75% relative humidity)with minimal variations in their quality attributes.展开更多
2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,...2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(I)with 2,29-dibenzothiazole disulfide(II)in the presence of triphenylphosphine.Effects of reaction time,temperature,solvents,catalysts and feeding molar ratio on the yield and quality of products were investigated,and an im-proved procedure suitable for industrial production was established.Using 1,2-dichloroethane as solvent,triphe-nylphosphine as reducer,and triethylamine as catalyst,n(I):n(II):n(triphenylphosphine)51.0:1.0:1.0,the product was obtained at room temperature in 98.1%yield.The purity of the product without further purification is 98.7%determined by HPLC method.This procedure could be a suitable alternative to the traditional processes because of its easy handling,high yield and low cost.展开更多
基金funded by the National Key Research and Development Program of China(2024YFC3506900)the Special Project for Technological Innovation in New Productive Forces of Modern Chinese Medicines(24ZXZKSY00010 and 24ZXZKSY00040)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002)。
文摘Extraction unit operation is the first step in traditional Chinese medicine(TCM)product manufacturing,and it is crucial in determining the quality of the produced medicine.However,due to a lack of effective multimodal monitoring and adjustment strategies,achieving high quality and efficiency remains a challenge.In this work,we proposed an artificial intelligence(AI)-based robot platform for the multi-objective optimization of the extraction process.First,a perception intelligence method for multimodal process monitoring was established to track active ingredient transfer and production changes during the extraction process.Second,a digital twin model was developed to reconstruct the field information,which interacted with real-time monitoring data.Furthermore,the model performed real-time inference to predict future production process states by using the reconstructing information.Finally,according to the predicted process states,the autonomous decision-making robot implemented multi-objective optimization,ensuring efficient process adjustments for global optimization.Experimental and industrial results demonstrated that the platform could effectively infer component transfer dynamics,monitor temperature variations,and identify boiling states,ensuring product quality while reducing energy consumption.This pharmaceutical robot could promote the integration of AI and pharmaceutical engineering,thereby accelerating the iterative development and improvement of China’s pharmaceutical industry.
基金Ministry of Education Singapore for funding this work(grant No.AcRF Tier 1 Fund RG4/24)and for the postgraduate scholarship awarded to Liu Han Ng.
文摘Ionic liquid(IL)salts of active pharmaceutical ingredients(API)represent promising formulations for poorly-soluble APIs as they eliminate polymorphism commonly associated with conventional API salts.Being highly viscous liquid,oral dosage formulation of API-ILs is challenging,necessitating immobilization onto particulate carriers,typically by spray-drying.This study developed an alternative oral dosage formulation of API-ILs by incorporating them into soft gelatin-alginate pellets,where the alginate’s role was to improve storage stability of hygroscopic and thermally-sensitive gelatin.Poorly-soluble ibuprofen(IBU)and 1-butyl-3-methylimidazolium(BMIM)was used as the model API-IL.The impacts of alginate inclusion at varying gelatin-to-alginate ratios on quality attributes of IBU-BMIM-loaded pellets were investigated.The evaluated attributes included physical appearance,IBU-BMIM payload,dosage uniformity,flowability,IBU-BMIM release,and IBU solubility enhancement.The results showed IBU-BMIM remained in its liquid-like amorphous form upon incorporation into the pellets,thereby preserving its solubility enhancement capability,albeit at a lower degree due to slower IBU-BMIM release upon alginate inclusion.Alginate inclusion also influenced the pellets’physical appearance,thickness,flowability,and gelatin’s secondary structures,while having minimal impacts on payload and dosage uniformity.Importantly,the pellets remained stable after one-month of accelerated storage(40℃ and 75% relative humidity)with minimal variations in their quality attributes.
文摘2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(I)with 2,29-dibenzothiazole disulfide(II)in the presence of triphenylphosphine.Effects of reaction time,temperature,solvents,catalysts and feeding molar ratio on the yield and quality of products were investigated,and an im-proved procedure suitable for industrial production was established.Using 1,2-dichloroethane as solvent,triphe-nylphosphine as reducer,and triethylamine as catalyst,n(I):n(II):n(triphenylphosphine)51.0:1.0:1.0,the product was obtained at room temperature in 98.1%yield.The purity of the product without further purification is 98.7%determined by HPLC method.This procedure could be a suitable alternative to the traditional processes because of its easy handling,high yield and low cost.
