title: Improvement of thymol properties by complexation with cyclodextrins: in vitro and in vivo studies.
abstract: Thymol, an effective agent for microbial diseases, has a low aqueous solubility and a strong bitter/irritating taste. These physicochemical characteristics need to be improved to develop pharmaceutical preparations. This study evaluates whether β-cyclodextrin and a copolymer based on dimethylaminoethyl methacrylate (DMAEMA) interact with thymol in order to control powderization, solubilization, and taste-masking properties. The thymol-β-cyclodextrin complex was prepared by co-precipitation and sealed-heating methods. The DMAEMA copolymer was mixed with the complex using a new approach, instead of spray coating, to decrease thymol volatility. In vivo studies were performed. Sealed-heating is a suitable method for including thymol in β-cyclodextrin with a good loading efficiency; thymol volatility control is achieved by mixing the complex with the DMAEMA copolymer. β-Cyclodextrin accelerates the in vivo thymol absorption rate compared with the free drug; the thymol half-life is still long. Therefore, a low number of administrations per day are required. Although bioavailability is unchanged with respect to free thymol, high doses could be administered of a selected formulation without compromising the compliance. Furthermore, thymol that is not absorbed is held along the intestine, where it can useful in the treatment and/or prevention of intestinal bacterial diseases.
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: marvi@uniss.it.
authors: Maria
authors: M
authors: Nieddu
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: grassu@uniss.it.
authors: Giovanna
authors: G
authors: Rassu
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: gboatto@uniss.it.
authors: Gianpiero
authors: G
authors: Boatto
authors: Dipartimento di Scienze e Tecnologie Agro-Alimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy. Electronic address: paolo.bosi@unibo.it.
authors: Paolo
authors: P
authors: Bosi
authors: Dipartimento di Scienze e Tecnologie Agro-Alimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy. Electronic address: paolo.trevisi@unibo.it.
authors: Paolo
authors: P
authors: Trevisi
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: pgiunc@uniss.it.
authors: Paolo
authors: P
authors: Giunchedi
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: acarta@uniss.it.
authors: Antonio
authors: A
authors: Carta
authors: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. Electronic address: eligav@uniss.it.
authors: Elisabetta
authors: E
authors: Gavini
mesh_terms: D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D041981:Gastrointestinal Tract / Q000378:metabolism; D006207:Half-Life; D066298:In Vitro Techniques; D008689:Methacrylates / Q000737:chemistry; D013552:Swine; D013943:Thymol / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D003505:Cyclodextrins; D008689:Methacrylates; D013943:Thymol; C049840:2-(dimethylamino)ethyl methacrylate
keywords: Cyclodextrin; Palatability improvement; Pharmacokinetic study; Sealed-heating; Thymol