title: The effect of PAMAM dendrimer concentration, generation size and surface functional group on the aqueous solubility of candesartan cilexetil.
abstract: This article investigates the aqueous solubility of the poorly soluble drug candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM) dendrimers. The effect of variables such as concentration, generation size (G2-G4), and surface groups (NH2, COOH and TRIS) of PAMAMs on the aqueous solubility of CC was studied. A two-factor factorial (3 × 3) ANOVA design was used to study the effect of generation size and surface functional group of the PAMAMs. The results showed that the aqueous solubility of CC in the presence of carboxyl and TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the effect of surface functional group of the PAMAMs on the aqueous solubility of CC was dependent on the generation size (p < 0.05). The sequence of the observed solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH (3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH2(91)>G3.NH2(50)>G2.NH2(37). The CC-PAMAM dendrimer inclusion complexes were characterized by UV-Vis, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques. Regarding the results of these techniques, improvement in the solubility of CC is expected primarily through the intermolecular hydrogen bonding between the drug and internal tertiary and surface functional groups of the studied PAMAMs.
authors.affiliation: a Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy , Adıyaman University , Adıyaman , Turkey.
authors.forename: Ali Serol
authors.initials: AS
authors.lastname: Ertürk
authors.affiliation: b Department of Chemistry , Yıldız Technical University , Istanbul , Turkey.
authors.forename: Mustafa Ulvi
authors.initials: MU
authors.lastname: Gürbüz
authors.affiliation: b Department of Chemistry , Yıldız Technical University , Istanbul , Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Tülü
mesh_terms: D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D012995:Solubility; D013777:Tetrazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D013777:Tetrazoles; D014867:Water; C077793:candesartan cilexetil
keywords: PAMAM dendrimers; candesartan cilexetil; inclusion complex; solubilization