Hydrogels based on chitosan–xanthan for controlled release of theophylline

Abstract

The aim of this paper is theophylline (THP) inclusion into xanthan-chitosan polyionic complex (Xa-CS) and the study of its in vitro and in vivo kinetic release. Xa-CS hydrogel was obtained by ionic complexation between two oppositely charged polysaccharides. THP was loaded into the Xa-CS matrix by diffusion of the drug solution. The obtained samples were characterized by FTIR spectroscopy, SEM microscopy and study of the swelling behavior. THP in vitro release experiments were carried out in conditions mimicking the gastrointestinal environment. The chosen drug dose for in vivo study was 15 mg THP/Kg body weight of THP powder or an equivalent dose in complex form. THP serum concentrations were determined by an HPLC assay. The THP peak serum concentration (C(max)) was 7.18 microg/ml for free THP and AUC(0-48) was 25.76 microg h/ml, while in the case of Xa-CS-THP, C(max) was of 5.72 microg/ml and AUC(0-48) = 45.72 microg h/ml. The in vivo study regarding the behaviour of the obtained formulation, showed an increase bioavailability of THP compared to the raw drug, suggesting the possible application of the complex Xa-CS as an oral controlled drug delivery system in the management of chronic pulmonary obstructive disease.

Properties of films obtained from biopolymers of different origins for skin lesions therapy

“…Polysaccharides such as chitosan (C), xanthan (X) and alginate are examples of non-toxic natural polymers used in the composition of materials for this purpose, being used alone or in combination with each other or with other compounds (Popa et al 2010;Fernandes et al 2011;Bellini et al 2012;Veiga and Moraes 2012). However, a major obstacle to their use is the variability in the characteristics of molecules resulting from different sources, which may result in changes in the properties of biomaterials obtained when these polymers are used.…”

“…When compared to polysaccharides extracted directly from the natural sources, such as alginate derived from seaweed, xanthan gum has the advantage of being independent of the production site and climatic conditions, which allows its production under significantly more controlled conditions, with lower variability in the properties of material originated from different batches and, therefore, with higher quality assurance. For this reason, xanthan gum, alone or combined with other polymers, has been gaining attention in the composition of biomaterials intended for different biomedical applications, such as devices for the controlled release of drugs (Popa et al 2010;Bellini et al 2012;Veiga and Moraes 2012;Dyondi et al 2013) and probiotic bacteria (Argin et al 2014), hydrogels for bone regeneration (Izawa et al 2014), ophthalmological materials (Ceulemans et al 2002;Ludwig 2005), implants (Kumar et al 2007) and scaffolds for tissue engineering Bellini et al 2012).…”

“…However, given that there is a tendency to avoid the use of materials from xenogenic origin for tissue engineering purposes and of complex composition, collagen replacement by compounds such as xanthan gum could provide additional benefits to such devices. The carboxyl groups in xanthan gum, when combined with the amines of chitosan, result in a microenvironment that favors the stabilization of proteins (Chellat et al 2000) and allows obtaining hydrogels (Dyondi et al 2013;Izawa et al 2014), tablets (Popa et al 2010) and films (Bejenariu et al 2008). The properties of membranes of chitosan combined with analytical grade xanthan gum in different reacting conditions were assessed in detail recently by Bellini et al (2012), which showed that these devices had appropriate characteristics for application as bioactive dermal dressings and as three-dimensional scaffolds for cell culture useful in the tissue engineering area.…”

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

“…These additives are capable of interacting with the polymer to attenuate release of the incorporated active drug (7,8). Theophylline, an alkaloid found in the leaves of Camellia sinensis is used clinically as a bronchodilator in the management of chronic obstructive pulmonary disease (9). Theophylline therapy of airways obstruction, associated with asthma and chronic bronchitis, with conventional immediate release regimen tablets or solutions requires treatment every six hours due to the short half-life of theophylline in the body and its narrow therapeutic index, with 5-20 mg mL -1 serum concentrations (9).…”

“…Theophylline, an alkaloid found in the leaves of Camellia sinensis is used clinically as a bronchodilator in the management of chronic obstructive pulmonary disease (9). Theophylline therapy of airways obstruction, associated with asthma and chronic bronchitis, with conventional immediate release regimen tablets or solutions requires treatment every six hours due to the short half-life of theophylline in the body and its narrow therapeutic index, with 5-20 mg mL -1 serum concentrations (9). Thus, sustained release dosage forms of theophylline can provide desirable serum concentrations for prolonged periods without frequent dosing, thereby providing patient compliance.…”