Pub Date : 2023-11-06DOI: 10.1186/s41120-023-00088-3
Kaushalendra Chaturvedi, Pasaorn Pongkulapa, Xiaoyi Ding, Harsh S. Shah, San Kiang, Veeran Kadajji
Abstract Coprocessing involves integration of multiple substances to improve the physical, chemical, mechanical, and biopharmaceutical properties of a material. Coprocessing is a promising technique in the pharmaceutical industry which support both drug substance and drug product processes. When active pharmaceutical ingredients (APIs) are coprocessed with excipients, it can enable direct compression and continuous manufacturing. Hydroxypropyl cellulose (HPC-L), a commonly used excipient in pharmaceutical formulations, can enhance drug stability, solubility, and bioavailability. In this study, we have employed coprecipitation (CPT) to coprocess metformin hydrochloride (MET) with HPC-L, resulting in the formation of agglomerates with improved physical attributes without any risk of polymorphic changes. Acetone/acetonitrile and heptane were used as solvent and antisolvent, respectively. Screening study revealed that the use of a rotor stator helps to control the size of metformin hydrochloride and HPC-L agglomerates (M-CPT) without negatively impacting bulk density and powder flow properties. The CPT agglomerates showed residual solvent levels within the specified ICH limits. Powder rheology results demonstrated a sixfold increase in FFC of M-CPT compared to neat MET. The compressibility, tabletability, compactability, and “In-Die” Heckel analysis data further suggested that the M-CPT agglomerates are directly compressible with no observable changes in the dissolution profile of MET. Overall, this study demonstrates application of CPT approach to tune the physical and mechanical properties, and HPC-L can be used as an excipient of choice for CPT technique to improve the compressibility and flowability of APIs. Graphical Abstract
{"title":"Enhancement of material attributes of poorly compressible metformin hydrochloride through coprocessing with hydroxypropyl cellulose (HPC-L) using coprecipitation (CPT)","authors":"Kaushalendra Chaturvedi, Pasaorn Pongkulapa, Xiaoyi Ding, Harsh S. Shah, San Kiang, Veeran Kadajji","doi":"10.1186/s41120-023-00088-3","DOIUrl":"https://doi.org/10.1186/s41120-023-00088-3","url":null,"abstract":"Abstract Coprocessing involves integration of multiple substances to improve the physical, chemical, mechanical, and biopharmaceutical properties of a material. Coprocessing is a promising technique in the pharmaceutical industry which support both drug substance and drug product processes. When active pharmaceutical ingredients (APIs) are coprocessed with excipients, it can enable direct compression and continuous manufacturing. Hydroxypropyl cellulose (HPC-L), a commonly used excipient in pharmaceutical formulations, can enhance drug stability, solubility, and bioavailability. In this study, we have employed coprecipitation (CPT) to coprocess metformin hydrochloride (MET) with HPC-L, resulting in the formation of agglomerates with improved physical attributes without any risk of polymorphic changes. Acetone/acetonitrile and heptane were used as solvent and antisolvent, respectively. Screening study revealed that the use of a rotor stator helps to control the size of metformin hydrochloride and HPC-L agglomerates (M-CPT) without negatively impacting bulk density and powder flow properties. The CPT agglomerates showed residual solvent levels within the specified ICH limits. Powder rheology results demonstrated a sixfold increase in FFC of M-CPT compared to neat MET. The compressibility, tabletability, compactability, and “In-Die” Heckel analysis data further suggested that the M-CPT agglomerates are directly compressible with no observable changes in the dissolution profile of MET. Overall, this study demonstrates application of CPT approach to tune the physical and mechanical properties, and HPC-L can be used as an excipient of choice for CPT technique to improve the compressibility and flowability of APIs. Graphical Abstract","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135585287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract The October 2022 draft United States Food and Drug Administration (FDA) guidance presents an option of in vitro release test (IVRT) studies as a biowaiver for topical drug products submitted in abbreviated new drug applications (ANDAs). However, the product-specific guidance (PSG) for 1% clotrimazole (CLZ) topical cream does not provide an in vitro option for biowaiver and requires a clinical endpoint study to demonstrate bioequivalence (BE). Therefore, the main objective was to use IVRT to investigate pharmaceutical equivalence of several 1% CLZ topical creams from two countries — South Africa (SA) and Canada. This investigation aims at demonstrating the utility of IVRT to determine ‘sameness’ and/or differences between topical creams containing 1% CLZ and the potential of IVRT for supporting biowaivers, thereby obviating the necessity to conduct clinical endpoint studies in patients. A validated IVRT method was applied to conduct comparative IVRT runs on five generic products marketed in SA and one Canadian generic, which were compared against a relevant comparator product from their country of origin in accordance with the FDA’s acceptance criteria of 75–133.33%. All five SA-marketed generic creams showed pharmaceutical inequivalence to the SA comparator product indicating Q1/Q2/Q3 differences. Despite containing the same excipients as both comparator products, the Canadian generic showed substantially lower release rate compared to the comparator products which could be attributed to Q2/Q3 differences. The IVRT method displayed the requisite ability to assess the various 1% CLZ creams and confirmed the potential of the IVRT method to support a biowaiver for 1% CLZ topical creams. Graphical Abstract
{"title":"Utility of in vitro release testing (IVRT) to assess ‘sameness’ of 1% clotrimazole creams for use as a biowaiver","authors":"Hannah Wellington, Seeprarani Rath, Sagaran Abboo, Isadore Kanfer","doi":"10.1186/s41120-023-00087-4","DOIUrl":"https://doi.org/10.1186/s41120-023-00087-4","url":null,"abstract":"Abstract The October 2022 draft United States Food and Drug Administration (FDA) guidance presents an option of in vitro release test (IVRT) studies as a biowaiver for topical drug products submitted in abbreviated new drug applications (ANDAs). However, the product-specific guidance (PSG) for 1% clotrimazole (CLZ) topical cream does not provide an in vitro option for biowaiver and requires a clinical endpoint study to demonstrate bioequivalence (BE). Therefore, the main objective was to use IVRT to investigate pharmaceutical equivalence of several 1% CLZ topical creams from two countries — South Africa (SA) and Canada. This investigation aims at demonstrating the utility of IVRT to determine ‘sameness’ and/or differences between topical creams containing 1% CLZ and the potential of IVRT for supporting biowaivers, thereby obviating the necessity to conduct clinical endpoint studies in patients. A validated IVRT method was applied to conduct comparative IVRT runs on five generic products marketed in SA and one Canadian generic, which were compared against a relevant comparator product from their country of origin in accordance with the FDA’s acceptance criteria of 75–133.33%. All five SA-marketed generic creams showed pharmaceutical inequivalence to the SA comparator product indicating Q1/Q2/Q3 differences. Despite containing the same excipients as both comparator products, the Canadian generic showed substantially lower release rate compared to the comparator products which could be attributed to Q2/Q3 differences. The IVRT method displayed the requisite ability to assess the various 1% CLZ creams and confirmed the potential of the IVRT method to support a biowaiver for 1% CLZ topical creams. Graphical Abstract","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"299 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135215857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-16DOI: 10.1186/s41120-023-00086-5
Dailenys Marrero-Morfa, César Ibarra-Alvarado, Francisco J. Luna-Vázquez, Miriam Estévez, Eremy Miranda Ledesma, Alejandra Rojas-Molina, Carlos T. Quirino-Barreda
Abstract Self-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and dose by the oral route. This research aimed to develop, through pseudo-ternary phase diagrams, a self-microemulsifying system prepared from an ethanolic extract of H. longipes root (HL-SMDS). In addition, the optimized lipid-based formulation was characterized and its in vitro gastrointestinal simulated dissolution was determined. The formulation composed of Transcutol, 55% (solubilizer); Tween80/PG, 10% (surfactant/co-solvent); Labrasol, 35% (surfactant); and the herbal extract was selected as optimal and identified as a SMEDDS, since when coming into contact with water, it forms a micro-emulsion with droplet sizes less than 100 nm. The stability tests showed that HL-SMDS remained stable over time under extreme conditions. Furthermore, the amount of affinin released from HL-SMDS at pH 1 and 6.8 was higher than that of the ethanolic extract from H. longipes root. These results indicate that HL-SMDS is a novel alternative to improve the aqueous solubility and therefore the oral bioavailability of the ethanolic extract of H. longipes root.
{"title":"Self-microemulsifying system of an ethanolic extract of Heliopsis longipes root for enhanced solubility and release of affinin","authors":"Dailenys Marrero-Morfa, César Ibarra-Alvarado, Francisco J. Luna-Vázquez, Miriam Estévez, Eremy Miranda Ledesma, Alejandra Rojas-Molina, Carlos T. Quirino-Barreda","doi":"10.1186/s41120-023-00086-5","DOIUrl":"https://doi.org/10.1186/s41120-023-00086-5","url":null,"abstract":"Abstract Self-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and dose by the oral route. This research aimed to develop, through pseudo-ternary phase diagrams, a self-microemulsifying system prepared from an ethanolic extract of H. longipes root (HL-SMDS). In addition, the optimized lipid-based formulation was characterized and its in vitro gastrointestinal simulated dissolution was determined. The formulation composed of Transcutol, 55% (solubilizer); Tween80/PG, 10% (surfactant/co-solvent); Labrasol, 35% (surfactant); and the herbal extract was selected as optimal and identified as a SMEDDS, since when coming into contact with water, it forms a micro-emulsion with droplet sizes less than 100 nm. The stability tests showed that HL-SMDS remained stable over time under extreme conditions. Furthermore, the amount of affinin released from HL-SMDS at pH 1 and 6.8 was higher than that of the ethanolic extract from H. longipes root. These results indicate that HL-SMDS is a novel alternative to improve the aqueous solubility and therefore the oral bioavailability of the ethanolic extract of H. longipes root.","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136077599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.1186/s41120-023-00083-8
Yaping Xu, Yue Wang, Chujie Li, Tao Han, Haiming Chen, Wenxue Chen, Qiuping Zhong, Jianfei Pei, Guido R. M. M. Haenen, Zhengwen Li, Mohamed Moalin, Ming Zhang, Weijun Chen
Abstract Dihydroquercetin (DHQ) is a natural occurring dihydroflavonol that has strong antioxidant and antibacterial activities. However, its application is limited due to its poor solubility. This study aims to improve the aqueous solubility of DHQ by complexing DHQ with β-cyclodextrin (β-CD) to boost its biological activity. DHQ was encapsulated with β-CD by freeze drying at a 1:1-M ratio. The structure of DHQ/β-CD complex prepared was elucidated by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and 1 H nuclear magnetic resonance ( 1 H NMR). In addition, molecular docking further revealed two energetically favorable conformations of the DHQ/β-CD complex, in which DHQ interacted with β-CD via hydrogen bonds. Experimental results showed that the solubility of the DHQ increased 22.63-fold by encapsulating with β-CD. Also the dissolution rate, antioxidant activity and antibacterial activity of the DHQ were significantly improved by encapsulating. The encapsulating with β-CD solves the problem of the poor aqueous solubility of DHQ, and broadens the path for a more optimal use of the health promoting effect of DHQ in pharmaceutical and food products.
{"title":"Preparation, characterization, and biological activity of the inclusion complex of dihydroquercetin and β-Cyclodextrin","authors":"Yaping Xu, Yue Wang, Chujie Li, Tao Han, Haiming Chen, Wenxue Chen, Qiuping Zhong, Jianfei Pei, Guido R. M. M. Haenen, Zhengwen Li, Mohamed Moalin, Ming Zhang, Weijun Chen","doi":"10.1186/s41120-023-00083-8","DOIUrl":"https://doi.org/10.1186/s41120-023-00083-8","url":null,"abstract":"Abstract Dihydroquercetin (DHQ) is a natural occurring dihydroflavonol that has strong antioxidant and antibacterial activities. However, its application is limited due to its poor solubility. This study aims to improve the aqueous solubility of DHQ by complexing DHQ with β-cyclodextrin (β-CD) to boost its biological activity. DHQ was encapsulated with β-CD by freeze drying at a 1:1-M ratio. The structure of DHQ/β-CD complex prepared was elucidated by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and 1 H nuclear magnetic resonance ( 1 H NMR). In addition, molecular docking further revealed two energetically favorable conformations of the DHQ/β-CD complex, in which DHQ interacted with β-CD via hydrogen bonds. Experimental results showed that the solubility of the DHQ increased 22.63-fold by encapsulating with β-CD. Also the dissolution rate, antioxidant activity and antibacterial activity of the DHQ were significantly improved by encapsulating. The encapsulating with β-CD solves the problem of the poor aqueous solubility of DHQ, and broadens the path for a more optimal use of the health promoting effect of DHQ in pharmaceutical and food products.","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135688721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-07DOI: 10.1186/s41120-023-00082-9
A. Yu, O. Ackaert
{"title":"Bioequivalence clinical trial simulation: a case study of apalutamide administered in applesauce versus whole tablets","authors":"A. Yu, O. Ackaert","doi":"10.1186/s41120-023-00082-9","DOIUrl":"https://doi.org/10.1186/s41120-023-00082-9","url":null,"abstract":"","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79161661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1186/s41120-023-00081-w
Martin Khoeiklang, Maria Wilhelm, Lingyun Li, Carol P. Moreno Quinn
{"title":"Compatibility study of patiromer with juices/liquids and soft foods","authors":"Martin Khoeiklang, Maria Wilhelm, Lingyun Li, Carol P. Moreno Quinn","doi":"10.1186/s41120-023-00081-w","DOIUrl":"https://doi.org/10.1186/s41120-023-00081-w","url":null,"abstract":"","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83253411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-03DOI: 10.1186/s41120-023-00080-x
Rana E. Elnady, M. Amin, Mohamed Y. Zakaria
{"title":"A review on lipid-based nanocarriers mimicking chylomicron and their potential in drug delivery and targeting infectious and cancerous diseases","authors":"Rana E. Elnady, M. Amin, Mohamed Y. Zakaria","doi":"10.1186/s41120-023-00080-x","DOIUrl":"https://doi.org/10.1186/s41120-023-00080-x","url":null,"abstract":"","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90931267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-04DOI: 10.1186/s41120-023-00076-7
S. M. Jakaria, D. Budil, James Murtagh
{"title":"Strategies to stabilize dalbavancin in aqueous solutions: Section 4—identification of heat degradation products in 2-hydroxypropyl-β-cyclodextrin and divalent metal ion solutions at pH 4.5 and 7.0","authors":"S. M. Jakaria, D. Budil, James Murtagh","doi":"10.1186/s41120-023-00076-7","DOIUrl":"https://doi.org/10.1186/s41120-023-00076-7","url":null,"abstract":"","PeriodicalId":453,"journal":{"name":"AAPS Open","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91035525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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