Solubilization of Nicardipine Hydrochloride via Complexation and Salt Formation
The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniq...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 1994-10, Vol.83 (10), p.1418-1420 |
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| container_title | Journal of pharmaceutical sciences |
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| creator | Maurin, Michael B. Rowe, Susan M. Koval, Christopher A. Hussain, Munir A. |
| description | The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a ∼10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5–6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine. |
| doi_str_mv | 10.1002/jps.2600831011 |
| format | Article |
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Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a ∼10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5–6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine.</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.2600831011</identifier><identifier>PMID: 7884662</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Washington: Elsevier Inc</publisher><subject>Antihypertensive agents ; Biological and medical sciences ; Buffers ; Cardiovascular system ; Chemical Phenomena ; Chemistry, Pharmaceutical ; Chemistry, Physical ; Evaluation Studies as Topic ; Hydrogen-Ion Concentration ; Medical sciences ; Nicardipine - chemistry ; Pharmacology. 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Pharm. Sci</addtitle><description>The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a ∼10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5–6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine.</description><subject>Antihypertensive agents</subject><subject>Biological and medical sciences</subject><subject>Buffers</subject><subject>Cardiovascular system</subject><subject>Chemical Phenomena</subject><subject>Chemistry, Pharmaceutical</subject><subject>Chemistry, Physical</subject><subject>Evaluation Studies as Topic</subject><subject>Hydrogen-Ion Concentration</subject><subject>Medical sciences</subject><subject>Nicardipine - chemistry</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maurin, Michael B.</creatorcontrib><creatorcontrib>Rowe, Susan M.</creatorcontrib><creatorcontrib>Koval, Christopher A.</creatorcontrib><creatorcontrib>Hussain, Munir A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maurin, Michael B.</au><au>Rowe, Susan M.</au><au>Koval, Christopher A.</au><au>Hussain, Munir A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Solubilization of Nicardipine Hydrochloride via Complexation and Salt Formation</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>1994-10</date><risdate>1994</risdate><volume>83</volume><issue>10</issue><spage>1418</spage><epage>1420</epage><pages>1418-1420</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a ∼10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5–6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine.</abstract><cop>Washington</cop><pub>Elsevier Inc</pub><pmid>7884662</pmid><doi>10.1002/jps.2600831011</doi><tpages>3</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Antihypertensive agents Biological and medical sciences Buffers Cardiovascular system Chemical Phenomena Chemistry, Pharmaceutical Chemistry, Physical Evaluation Studies as Topic Hydrogen-Ion Concentration Medical sciences Nicardipine - chemistry Pharmacology. Drug treatments Solubility |
| title | Solubilization of Nicardipine Hydrochloride via Complexation and Salt Formation |
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