The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins.
Telmisartan (TEL) was entrapped into β-cyclodextrin aiming the improvement of its biopharmaceutical properties of low solubility. A solid state grinding process was used to prepare the molecular inclusion complex (MIC) for up to 30min. The inclusion ratio of drug and β-cyclodextrin was established as 1:2 and 1:3 (mol/mol) by phase solubility study and Job Plot. DSC, XRPD and FTIR confirmed the molecular interactions between TEL and β-cyclodextrin. Computer molecular modeling supports the presence of hydrogen bonds between guest and host and demonstrated the most probable complexes configuration. MIC_1:2_30 and MIC_1:3_30 enhanced the dissolution rate of the drug achieving a delivery rate comparable with the reference medicine available in the market (81% and 87% in 5min, for MIC_1:3_30 and Micardis(®), respectively). These formulations showed rapid and effective antihypertensive effect against angiotensin II in rats up to 180min, with statistically significant results against placebo and control in the first 30min after administration.
Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Trindade, 88040-970 Florianópolis, SC, Brazil.
Paola Aline Amarante
PA
Borba
Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Trindade, 88040-970 Florianópolis, SC, Brazil.
Marihá
M
Pinotti
Programa de Pós-Graduação em Engenharia e Ciências dos Materiais, Universidade Federal do Sergipe, Campus São Cristóvão, 49000-100, São Cristóvão, SE, Brazil.
George Ricardo Santana
GR
Andrade
Programa de Pós-Graduação em Engenharia e Ciências dos Materiais, Universidade Federal do Sergipe, Campus São Cristóvão, 49000-100, São Cristóvão, SE, Brazil; Departamento de Química, Universidade Federal do Sergipe, Campus São Cristóvão, 49000-100, São Cristóvão, SE, Brazil.
Nivan Bezerra
NB
da Costa
Departamento de Ciências Farmacêuticas, Universidade Estadual de Ponta Grossa, Campus Uvaranas, 84030-900 PR, Brazil.
Luiz Renato
LR
Olchanheski Junior
Departamento de Ciências Farmacêuticas, Universidade Estadual de Ponta Grossa, Campus Uvaranas, 84030-900 PR, Brazil.
Daniel
D
Fernandes
Departamento de Física, Universidade Federal de Santa Catarina, Campus Trindade, 88040-970 Florianópolis, SC, Brazil.
Carlos Eduardo Maduro
CE
de Campos
Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Trindade, 88040-970 Florianópolis, SC, Brazil. Electronic address: hellen.stulzer@gmail.com.
Hellen Karine
HK
Stulzer
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002626:Chemistry, Pharmaceutical; D005260:Female; D055595:Mechanical Phenomena; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D000077333:Telmisartan; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D047392:beta-Cyclodextrins; C031215:betadex; D000077333:Telmisartan
In vivo studies; Mechanical grinding process; Molecular inclusion complex; Molecular modeling; Telmisartan; β-Cyclodextrin