Improved pharmacokinetic and pharmacodynamic attributes of artemether–lumefantrine‐loaded solid SMEDDS for oral administration
Objectives To evaluate the in‐vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine. Methods Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S‐SMEDDS were evaluated for red...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2017-11, Vol.69 (11), p.1437-1446 |
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| container_title | Journal of pharmacy and pharmacology |
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| creator | Bhandari, Sameer Bhandari, Vikram Sood, Jatin Jaswal, Sunil Rana, Vikas Bedi, Neena Sehgal, Rakesh Tiwary, Ashok K. |
| description | Objectives
To evaluate the in‐vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.
Methods
Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S‐SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice. Haematology, biochemical parameters and histopathology were performed for evaluating safety of formulation. Pharmacokinetic characterization of both drugs was performed after oral administration in rats.
Key findings
Optimized solid SMEDDS containing low, medium and high dose were more effective in reducing parasitemia and mortality of mice as compared to marketed tablets containing high dose of these drugs. Single oral administration of solid SMEDDS containing high‐dose combination could maintain plasma concentration of lumefantrine above the minimum effective concentration for ≈4 days.
Conclusions
Solid SMEDDS containing low‐, medium‐ and high‐dose combination of artemether and lumefantrine are more effective than marketed tablets. |
| doi_str_mv | 10.1111/jphp.12795 |
| format | Article |
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To evaluate the in‐vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.
Methods
Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S‐SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice. Haematology, biochemical parameters and histopathology were performed for evaluating safety of formulation. Pharmacokinetic characterization of both drugs was performed after oral administration in rats.
Key findings
Optimized solid SMEDDS containing low, medium and high dose were more effective in reducing parasitemia and mortality of mice as compared to marketed tablets containing high dose of these drugs. Single oral administration of solid SMEDDS containing high‐dose combination could maintain plasma concentration of lumefantrine above the minimum effective concentration for ≈4 days.
Conclusions
Solid SMEDDS containing low‐, medium‐ and high‐dose combination of artemether and lumefantrine are more effective than marketed tablets.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/jphp.12795</identifier><identifier>PMID: 28809448</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Administration, Oral ; Animals ; Antimalarials - administration & dosage ; Antimalarials - pharmacokinetics ; Antimalarials - toxicity ; Artemether ; Artemisinins - administration & dosage ; Artemisinins - pharmacokinetics ; Artemisinins - toxicity ; Chemistry, Pharmaceutical ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Compounding ; Drug Delivery Systems ; Drug dosages ; Drying ; Emulsions ; Ethanolamines - administration & dosage ; Ethanolamines - pharmacokinetics ; Ethanolamines - toxicity ; Female ; Fluorenes - administration & dosage ; Fluorenes - pharmacokinetics ; Fluorenes - toxicity ; Histopathology ; lumefantrine ; Male ; Mice ; Mortality ; Oral administration ; Parasitemia ; Pharmacodynamics ; Pharmacokinetics ; Rats ; Rats, Wistar ; Rodents ; solid SMEDDS ; Spray drying ; Subacute toxicity ; Tablets ; Toxicity</subject><ispartof>Journal of pharmacy and pharmacology, 2017-11, Vol.69 (11), p.1437-1446</ispartof><rights>2017 Royal Pharmaceutical Society</rights><rights>2017 Royal Pharmaceutical Society.</rights><rights>Copyright © 2017 Royal Pharmaceutical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3575-9613a51a54c978662a03b6c987103d1529c1f03553d428b7c6fd538c75c6ed183</citedby><cites>FETCH-LOGICAL-c3575-9613a51a54c978662a03b6c987103d1529c1f03553d428b7c6fd538c75c6ed183</cites><orcidid>0000-0002-7734-7892</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjphp.12795$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjphp.12795$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28809448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhandari, Sameer</creatorcontrib><creatorcontrib>Bhandari, Vikram</creatorcontrib><creatorcontrib>Sood, Jatin</creatorcontrib><creatorcontrib>Jaswal, Sunil</creatorcontrib><creatorcontrib>Rana, Vikas</creatorcontrib><creatorcontrib>Bedi, Neena</creatorcontrib><creatorcontrib>Sehgal, Rakesh</creatorcontrib><creatorcontrib>Tiwary, Ashok K.</creatorcontrib><title>Improved pharmacokinetic and pharmacodynamic attributes of artemether–lumefantrine‐loaded solid SMEDDS for oral administration</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>Objectives
To evaluate the in‐vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.
Methods
Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S‐SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice. Haematology, biochemical parameters and histopathology were performed for evaluating safety of formulation. Pharmacokinetic characterization of both drugs was performed after oral administration in rats.
Key findings
Optimized solid SMEDDS containing low, medium and high dose were more effective in reducing parasitemia and mortality of mice as compared to marketed tablets containing high dose of these drugs. Single oral administration of solid SMEDDS containing high‐dose combination could maintain plasma concentration of lumefantrine above the minimum effective concentration for ≈4 days.
Conclusions
Solid SMEDDS containing low‐, medium‐ and high‐dose combination of artemether and lumefantrine are more effective than marketed tablets.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - pharmacokinetics</subject><subject>Antimalarials - toxicity</subject><subject>Artemether</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - pharmacokinetics</subject><subject>Artemisinins - toxicity</subject><subject>Chemistry, Pharmaceutical</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Combinations</subject><subject>Drug Compounding</subject><subject>Drug Delivery Systems</subject><subject>Drug dosages</subject><subject>Drying</subject><subject>Emulsions</subject><subject>Ethanolamines - administration & dosage</subject><subject>Ethanolamines - pharmacokinetics</subject><subject>Ethanolamines - toxicity</subject><subject>Female</subject><subject>Fluorenes - administration & dosage</subject><subject>Fluorenes - pharmacokinetics</subject><subject>Fluorenes - toxicity</subject><subject>Histopathology</subject><subject>lumefantrine</subject><subject>Male</subject><subject>Mice</subject><subject>Mortality</subject><subject>Oral administration</subject><subject>Parasitemia</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>solid SMEDDS</subject><subject>Spray drying</subject><subject>Subacute toxicity</subject><subject>Tablets</subject><subject>Toxicity</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMoOo5ufAApuBOquTRpuhTHy4iioK5LJkmZjG1Tk1SZnfgEgm_ok5hxvOw8mwPnfHyH8wOwg-ABinU466bdAcJ5QVfAAMMMpzmifBUMIMQ4JTQnG2DT-xmEMGeMrYMNzDkssowPwOu46Zx90irppsI1QtoH0-pgZCLav5mat6JZzEJwZtIH7RNbJcIF3egw1e7j5b3uG12JNu5b_fHyVluhotTb2qjk9upkNLpNKusS60SdCNWY1vjgRDC23QJrlai93v7uQ3B_enJ3fJ5eXp-Nj48uUxlfoGnBEBEUCZrJIueMYQHJhMmC5wgShSguJKogoZSoDPNJLlmlKOEyp5JphTgZgr2lNz782GsfypntXRtPlqjIGCfxTBGp_SUlnfXe6arsnGmEm5cIlou4y0Xc5VfcEd79VvaTRqtf9CffCKAl8GxqPf9HVV7cnN8spZ9oB45u</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Bhandari, Sameer</creator><creator>Bhandari, Vikram</creator><creator>Sood, Jatin</creator><creator>Jaswal, Sunil</creator><creator>Rana, Vikas</creator><creator>Bedi, Neena</creator><creator>Sehgal, Rakesh</creator><creator>Tiwary, Ashok K.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><orcidid>https://orcid.org/0000-0002-7734-7892</orcidid></search><sort><creationdate>201711</creationdate><title>Improved pharmacokinetic and pharmacodynamic attributes of artemether–lumefantrine‐loaded solid SMEDDS for oral administration</title><author>Bhandari, Sameer ; Bhandari, Vikram ; Sood, Jatin ; Jaswal, Sunil ; Rana, Vikas ; Bedi, Neena ; Sehgal, Rakesh ; Tiwary, Ashok K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3575-9613a51a54c978662a03b6c987103d1529c1f03553d428b7c6fd538c75c6ed183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - pharmacokinetics</topic><topic>Antimalarials - toxicity</topic><topic>Artemether</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - pharmacokinetics</topic><topic>Artemisinins - toxicity</topic><topic>Chemistry, Pharmaceutical</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Combinations</topic><topic>Drug Compounding</topic><topic>Drug Delivery Systems</topic><topic>Drug dosages</topic><topic>Drying</topic><topic>Emulsions</topic><topic>Ethanolamines - administration & dosage</topic><topic>Ethanolamines - pharmacokinetics</topic><topic>Ethanolamines - toxicity</topic><topic>Female</topic><topic>Fluorenes - administration & dosage</topic><topic>Fluorenes - pharmacokinetics</topic><topic>Fluorenes - toxicity</topic><topic>Histopathology</topic><topic>lumefantrine</topic><topic>Male</topic><topic>Mice</topic><topic>Mortality</topic><topic>Oral administration</topic><topic>Parasitemia</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>solid SMEDDS</topic><topic>Spray drying</topic><topic>Subacute toxicity</topic><topic>Tablets</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhandari, Sameer</creatorcontrib><creatorcontrib>Bhandari, Vikram</creatorcontrib><creatorcontrib>Sood, Jatin</creatorcontrib><creatorcontrib>Jaswal, Sunil</creatorcontrib><creatorcontrib>Rana, Vikas</creatorcontrib><creatorcontrib>Bedi, Neena</creatorcontrib><creatorcontrib>Sehgal, Rakesh</creatorcontrib><creatorcontrib>Tiwary, Ashok K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhandari, Sameer</au><au>Bhandari, Vikram</au><au>Sood, Jatin</au><au>Jaswal, Sunil</au><au>Rana, Vikas</au><au>Bedi, Neena</au><au>Sehgal, Rakesh</au><au>Tiwary, Ashok K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved pharmacokinetic and pharmacodynamic attributes of artemether–lumefantrine‐loaded solid SMEDDS for oral administration</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2017-11</date><risdate>2017</risdate><volume>69</volume><issue>11</issue><spage>1437</spage><epage>1446</epage><pages>1437-1446</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Objectives
To evaluate the in‐vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.
Methods
Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S‐SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice. Haematology, biochemical parameters and histopathology were performed for evaluating safety of formulation. Pharmacokinetic characterization of both drugs was performed after oral administration in rats.
Key findings
Optimized solid SMEDDS containing low, medium and high dose were more effective in reducing parasitemia and mortality of mice as compared to marketed tablets containing high dose of these drugs. Single oral administration of solid SMEDDS containing high‐dose combination could maintain plasma concentration of lumefantrine above the minimum effective concentration for ≈4 days.
Conclusions
Solid SMEDDS containing low‐, medium‐ and high‐dose combination of artemether and lumefantrine are more effective than marketed tablets.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28809448</pmid><doi>10.1111/jphp.12795</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7734-7892</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3573 |
| ispartof | Journal of pharmacy and pharmacology, 2017-11, Vol.69 (11), p.1437-1446 |
| issn | 0022-3573 2042-7158 |
| language | eng |
| recordid | cdi_proquest_journals_1946833579 |
| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Administration, Oral Animals Antimalarials - administration & dosage Antimalarials - pharmacokinetics Antimalarials - toxicity Artemether Artemisinins - administration & dosage Artemisinins - pharmacokinetics Artemisinins - toxicity Chemistry, Pharmaceutical Dose-Response Relationship, Drug Drug Combinations Drug Compounding Drug Delivery Systems Drug dosages Drying Emulsions Ethanolamines - administration & dosage Ethanolamines - pharmacokinetics Ethanolamines - toxicity Female Fluorenes - administration & dosage Fluorenes - pharmacokinetics Fluorenes - toxicity Histopathology lumefantrine Male Mice Mortality Oral administration Parasitemia Pharmacodynamics Pharmacokinetics Rats Rats, Wistar Rodents solid SMEDDS Spray drying Subacute toxicity Tablets Toxicity |
| title | Improved pharmacokinetic and pharmacodynamic attributes of artemether–lumefantrine‐loaded solid SMEDDS for oral administration |
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