In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment

[Display omitted] Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. To test the hypothesis that a sustained delivery system...

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Veröffentlicht in:International journal of pharmaceutics 2019-02, Vol.557, p.53-65
Hauptverfasser: Ivanova, Nadezhda Antonova, Trapani, Adriana, Franco, Cinzia Di, Mandracchia, Delia, Trapani, Giuseppe, Franchini, Carlo, Corbo, Filomena, Tripodo, Giuseppe, Kolev, Iliyan Nikolov, Stoyanov, Georgi Stoyanov, Bratoeva, Kameliya Zhechkova
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container_title International journal of pharmaceutics
container_volume 557
creator Ivanova, Nadezhda Antonova
Trapani, Adriana
Franco, Cinzia Di
Mandracchia, Delia
Trapani, Giuseppe
Franchini, Carlo
Corbo, Filomena
Tripodo, Giuseppe
Kolev, Iliyan Nikolov
Stoyanov, Georgi Stoyanov
Bratoeva, Kameliya Zhechkova
description [Display omitted] Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. To test the hypothesis that a sustained delivery system of diltiazem hydrochloride may be helpful for the treatment of chronic anal fissures, in the present study we evaluated the potential of gels containing diltiazem hydrochloride entrapped in microsponges. Such microsponges were based on Eudragit RS 100 and the effect of some formulation variables was assessed by a 23 full factorial screening design. An optimized formulation of diltiazem hydrochloride microsponges was dispersed in Methylcellulose 2% or Poloxamer 407 20% and the resulting gels (micro-l-diltiazem hydrochloride 2%) were subjected to in vitro drug release, ex vivo permeability and drug deposition after application on porcine rectal mucosa. The results showed a prolonged release up to 24 h from micro-l-diltiazem hydrochloride at 2% in the gels. The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy.
doi_str_mv 10.1016/j.ijpharm.2018.12.039
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The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2018.12.039</identifier><identifier>PMID: 30580086</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Chronic anal fissures ; Diltiazem hydrochloride ; Factorial screening design ; Microsponges ; Permeation ; Rectal gels</subject><ispartof>International journal of pharmaceutics, 2019-02, Vol.557, p.53-65</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. 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The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy.</description><subject>Chronic anal fissures</subject><subject>Diltiazem hydrochloride</subject><subject>Factorial screening design</subject><subject>Microsponges</subject><subject>Permeation</subject><subject>Rectal gels</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkE1v1DAQhi0EokvhJ4B85JIwtrOJc0Ko4qNSJS5wthx73PUqsRfbWVEO_Ha82qXXnkYzeuYdzUPIWwYtA9Z_2Ld-f9jptLQcmGwZb0GMz8iGyUE0ohv652QDYpDNlg3iirzKeQ8APWfiJbkSsJUAst-Qv7eBHn1JkepgKf6uzTHSXFbrMdMYqPVz8foPLnT3YFM0uzkmb7GZo7Zo6eJNivkQw33FfaAJTdEzvcc5UxcTNbsUgzc1vU6dz3lNFSwJdVkwlNfkhdNzxjeXek1-fvn84-Zbc_f96-3Np7vGdIyXBiVOVoPuuhHQ9ZMehWVbkNwZbQfHJqFHLpyYzDDKjjkE6azsTY8jlxaFuCbvz7mHFH-tmItafDY4zzpgXLPirIcaWLVUdHtGT4_lhE4dkl90elAM1Em92quLenVSrxhXVX3de3c5sU4L2set_64r8PEMVDd49JhUNh6DQetP1pSN_okT_wAPVJtT</recordid><startdate>20190225</startdate><enddate>20190225</enddate><creator>Ivanova, Nadezhda Antonova</creator><creator>Trapani, Adriana</creator><creator>Franco, Cinzia Di</creator><creator>Mandracchia, Delia</creator><creator>Trapani, Giuseppe</creator><creator>Franchini, Carlo</creator><creator>Corbo, Filomena</creator><creator>Tripodo, Giuseppe</creator><creator>Kolev, Iliyan Nikolov</creator><creator>Stoyanov, Georgi Stoyanov</creator><creator>Bratoeva, Kameliya Zhechkova</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6951-1103</orcidid><orcidid>https://orcid.org/0000-0001-5462-5629</orcidid></search><sort><creationdate>20190225</creationdate><title>In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment</title><author>Ivanova, Nadezhda Antonova ; Trapani, Adriana ; Franco, Cinzia Di ; Mandracchia, Delia ; Trapani, Giuseppe ; Franchini, Carlo ; Corbo, Filomena ; Tripodo, Giuseppe ; Kolev, Iliyan Nikolov ; Stoyanov, Georgi Stoyanov ; Bratoeva, Kameliya Zhechkova</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-e8ebda0a4490ef6ba93d15082fcad7f1b3a923f3bc79841fe08fd86c6e928de33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Chronic anal fissures</topic><topic>Diltiazem hydrochloride</topic><topic>Factorial screening design</topic><topic>Microsponges</topic><topic>Permeation</topic><topic>Rectal gels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ivanova, Nadezhda Antonova</creatorcontrib><creatorcontrib>Trapani, Adriana</creatorcontrib><creatorcontrib>Franco, Cinzia Di</creatorcontrib><creatorcontrib>Mandracchia, Delia</creatorcontrib><creatorcontrib>Trapani, Giuseppe</creatorcontrib><creatorcontrib>Franchini, Carlo</creatorcontrib><creatorcontrib>Corbo, Filomena</creatorcontrib><creatorcontrib>Tripodo, Giuseppe</creatorcontrib><creatorcontrib>Kolev, Iliyan Nikolov</creatorcontrib><creatorcontrib>Stoyanov, Georgi Stoyanov</creatorcontrib><creatorcontrib>Bratoeva, Kameliya Zhechkova</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ivanova, Nadezhda Antonova</au><au>Trapani, Adriana</au><au>Franco, Cinzia Di</au><au>Mandracchia, Delia</au><au>Trapani, Giuseppe</au><au>Franchini, Carlo</au><au>Corbo, Filomena</au><au>Tripodo, Giuseppe</au><au>Kolev, Iliyan Nikolov</au><au>Stoyanov, Georgi Stoyanov</au><au>Bratoeva, Kameliya Zhechkova</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2019-02-25</date><risdate>2019</risdate><volume>557</volume><spage>53</spage><epage>65</epage><pages>53-65</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted] Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. 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subjects Chronic anal fissures
Diltiazem hydrochloride
Factorial screening design
Microsponges
Permeation
Rectal gels
title In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment
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