@article{
author = "Homšek, Irena and Cvetković, Nebojša and Marić, Ljiljana and Spasić, Aleksandra and Ivić, Branka and Erić, Slavica",
year = "2012",
abstract = "Telmisartan acts as antagonist of angiotensin II type-1 (AT1) receptor and is indicated in the treatment of essential hypertension. In order to rationalize the pharmacokinetic characteristics, pharmacological activity, as well as the optimal method of administration of this drug, knowledge of its physico-chemical properties is needed. The assessment of the drug physico-chemical parameters on the basis of its chemical structure at different pH values, which are characteristic for physiological conditions, enables the prediction of its behaviour in the body before the drug is synthesized. Such assessment of its physico-chemical parameters during the preformulation phase is important for the development of a safe, efficient and stable dosage form. Based on the calculated pKa values, this paper is focused on the prediction of distribution of the ionized and nonionized drug species in the pH gradient of 1 to 8 and the calculation of physico-chemical parameters such as telmisartan lipophilicity (log P) and intrinsic solubility (log S0). On the basis of the calculated physicochemical parameters, the pH-dependent solubility and lipophilicity curves of this medicinal substance have been constructed. The assessment of intrinsic dissolution rate and dissolution rate of telmisartan from tablets was used to investigate the influence of medium pH values applied on the model substance behavior. The results obtained from predicting the physico-chemical properties and from experimental evaluation of the model substance intrinsic dissolution rate and telmisartan dissolution rate from tablets, indicate the importance of physico-chemical characterization of the active substance during the preformulation investigation for predicting the drug behaviour in the body (absorption, bioavailability, tissue penetration, elimination). ., Telmisartan deluje kao antagonista angiotenzinskog II tipa-1 (AT1) receptora i indikovan je u terapiji esencijalne hipertenzije. Da bi se razjasnile farmakokinetičke osobine, farmakološka aktivnost, kao i optimalni način primene ove lekovite supstance, potrebno je poznavanje njenih fizičko-hemijskih osobina. Određivanje fizičko-hemijskih parametara lekovite supstance na osnovu hemijske strukture pri različitim pH vrednostima koje su karakteristične za fiziološke uslove omogućava predviđanje njenog ponašanja u organizmu pre nego što se lekovita supstanca sintetiše. Određivanje fizičko-hemijskih parametara u toku preformulacionih ispitivanja značajno je za razvijanje bezbednog, efikasnog i stabilnog farmaceutskog oblika. U ovom radu je, na osnovu izračunatih pKa vrednosti, izvršeno predviđanje raspodele jonizovanih i nejonizivanog oblika lekovite supstance u pH gradijentu od 1 do 8 i izračunavanje fizičko-hemijskih parametara telmisartana kao što su lipofilnost (log P) i osnovna rastvorljivost (log S0). Na osnovu izračunatih fizičko-hemijskih parametara konstruisane su krive pH-zavisne rastvorljivosti i lipofilnosti ove lekovite supstance. Određivanjem osnovnih brzina rastvaranja i brzina rastvaranja telmisartana iz tableta ispitan je uticaj pH vrednosti primenjenog medijuma na ponašanje model supstance. Rezultati dobijeni predviđanjem fizičko-hemijskih osobina, kao i eksperimentalnim određivanjem osnovne brzine rastvaranja model supstance i brzine rastvaranja telmisartana iz tableta ukazuju na značaj fizičko-hemijske karakterizacije aktivne supstance tokom preformulacionih ispitivanja za predviđanje njenog ponašanja u organizmu (resorpcije, biološke raspoloživosti, penetracije u tkiva, eliminacije).",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "In vitro/in silico investigation of the drug substance and telmisartan tablets, In vitro/in silico ispitivanje lekovite supstance i tableta telmisartana",
volume = "62",
number = "6",
pages = "548-561",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1812"
}
