Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles
Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodext...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Universidade de São Paulo
2019-11-01
|
| Series: | Brazilian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502019000100551&tlng=en |
| _version_ | 1818368082149638144 |
|---|---|
| author | Leticia Norma Carpentieri Rodrigues Anna Carollina Moraes Tavares Beatriz Tavares Ferreira Adriana Karla Cardoso Amorim Reis Luciana Morita Katiki |
| author_facet | Leticia Norma Carpentieri Rodrigues Anna Carollina Moraes Tavares Beatriz Tavares Ferreira Adriana Karla Cardoso Amorim Reis Luciana Morita Katiki |
| author_sort | Leticia Norma Carpentieri Rodrigues |
| collection | DOAJ |
| description | Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, β-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-β-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 μg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-β-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates. |
| first_indexed | 2024-12-13T23:02:17Z |
| format | Article |
| id | doaj.art-c1965d5147ed460f8d9e56c03006feb1 |
| institution | Directory Open Access Journal |
| issn | 2175-9790 |
| language | English |
| last_indexed | 2024-12-13T23:02:17Z |
| publishDate | 2019-11-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-c1965d5147ed460f8d9e56c03006feb12022-12-21T23:28:23ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902019-11-015510.1590/s2175-97902019000117776Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazolesLeticia Norma Carpentieri Rodrigueshttps://orcid.org/0000-0001-5175-859XAnna Carollina Moraes TavaresBeatriz Tavares FerreiraAdriana Karla Cardoso Amorim ReisLuciana Morita KatikiAlbendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (β-cyclodextrin and hydroxypropyl-β-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, β-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-β-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 μg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-β-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502019000100551&tlng=enCyclodextrins/pharmacokineticsBenzimidazoles/administration & dosageInclusion complexesCyclodextrin aggregatesDrug liberation/drug effectsAntiparasitic agents/analysisAlbendazole/analysisFenbendazole/analysis |
| spellingShingle | Leticia Norma Carpentieri Rodrigues Anna Carollina Moraes Tavares Beatriz Tavares Ferreira Adriana Karla Cardoso Amorim Reis Luciana Morita Katiki Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles Brazilian Journal of Pharmaceutical Sciences Cyclodextrins/pharmacokinetics Benzimidazoles/administration & dosage Inclusion complexes Cyclodextrin aggregates Drug liberation/drug effects Antiparasitic agents/analysis Albendazole/analysis Fenbendazole/analysis |
| title | Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| title_full | Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| title_fullStr | Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| title_full_unstemmed | Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| title_short | Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| title_sort | inclusion complexes and self assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles |
| topic | Cyclodextrins/pharmacokinetics Benzimidazoles/administration & dosage Inclusion complexes Cyclodextrin aggregates Drug liberation/drug effects Antiparasitic agents/analysis Albendazole/analysis Fenbendazole/analysis |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502019000100551&tlng=en |
| work_keys_str_mv | AT leticianormacarpentierirodrigues inclusioncomplexesandselfassembledcyclodextrinaggregatesforincreasingthesolubilityofbenzimidazoles AT annacarollinamoraestavares inclusioncomplexesandselfassembledcyclodextrinaggregatesforincreasingthesolubilityofbenzimidazoles AT beatriztavaresferreira inclusioncomplexesandselfassembledcyclodextrinaggregatesforincreasingthesolubilityofbenzimidazoles AT adrianakarlacardosoamorimreis inclusioncomplexesandselfassembledcyclodextrinaggregatesforincreasingthesolubilityofbenzimidazoles AT lucianamoritakatiki inclusioncomplexesandselfassembledcyclodextrinaggregatesforincreasingthesolubilityofbenzimidazoles |