In vitro release of theophylline from starch-based matrices prepared via high hydrostatic pressure treatment and autoclaving

Highlights

• Physically modified starches were successfully used as carriers for theophylline.

• High pressure treatment and autoclaving affected drug release kinetics.

• Amylopectin starch matrices exhibited controlled theophylline release.

• Matrix morphology was found to be a key factor affecting theophylline dissolution.

Abstract

Recent works have demonstrated that release behavior of bioactive compounds varies with the nature of the matrix regarding its chemical composition, morphology and surface properties. Starch matrices varying in amylose content (maize, sorghum, Hylon VII) or pure amylopectin ones (waxy maize, amaranth starch), containing theophylline (10 mg, 50 mg/0.5 g of starch), were obtained via high hydrostatic pressure treatment (650 MPa/9 min) and autoclaving (120 °C/20 min). Both the treatment used and drug dose affected the theophylline release profiles from the matrices studied. The profiles of amylopectin starch matrices satisfactorily fitted with selected mathematical models, indicating a controlled theophylline release. The principal component analysis confirmed substantial differences in drug release between the amylose and amylopectin matrices. The differences in matrix morphology, internal surface area and porosity (mesopore diameter, cumulative pore volume) between the matrices studied were found to be key factors affecting the theophylline dissolution.

Introduction

As a biodegradable polymer with simple and well-defined chemical properties, starch is widely used in the food and non-food industry. To meet steadily increasing demands for improved specific starch properties, its granules are subjected to chemical or physical treatment (Pei-Ling, Qing, Qun, Xiao-Song, & Ji-Hong, 2012). Starch and its derivatives were successfully adopted to develop carriers for bioactive compounds or as a matrices/hydrogels for controlled drug delivery (Lopez-Cordoba et al., 2014, Xiao, 2013, Nair and Jyothi, 2013, Ismail et al., 2013). Among different modifications and derivatization methods applied to produce new starch material from native granules, high hydrostatic pressure (HP) has attracted much attention as a non-thermal processing technology (Pei-Ling et al., 2012).

Although, HP has been defined as a “mild technology”, it yields effective changes in the structure and in the physicochemical properties of starch granules (Pei-Ling et al., 2012). Starches composed of mainly amylopectin when subjected to HP treatment in excess of water was capable of forming an amorphous, three-dimensional network structure (Błaszczak, Wasserman, Fornal, & Yuryev, 2007). On the contrary, starches with medium and high concentration of amylose maintained their granular shape under HHP and demonstrated limited swelling and amylose release (Vallons & Arendt, 2009). The susceptibility (rate and degree) of HP-treated starches to retrogradation, their resistance to enzymatic activity or swelling power may differ significantly from those properties displayed by heat-gelatinized granules (Pei-Ling et al., 2012).

Hydrophilic matrices, including starch hydrogels produced via HP (Szepes et al., 2008) or these obtained by hydrothermal treatment and subsequent retrogradation (Yoon, Lee & Lim, 2009) have been recognized as interesting material for application in drug release formulation. They may be used for controlled release of both water-soluble and water-insoluble active compounds (Bialleck and Rein, 2011, Nair and Jyothi, 2013).

Theophylline as a model drug has been widely analyzed in various release systems (tablet, capsule, solution) since it demonstrated almost constant solubility (1 g/120 mL) in a wide range of pH values (Yoon et al., 2009). Since theophylline manifested narrow therapeutic range, it is crucial to investigate the differences in release rate of this drug between formulations (Wolny, Gruchlik, Chodurek, Szara, & Dzierżewicz, 2012). Recent works have demonstrated that the release behavior of theophylline varies with the nature of the matrix, and can be controlled among others through its chemical composition, method of formulation used and/or its physical properties (Nair & Jyothi, 2013).

Ultrahigh hydrostatic pressure as an attractive physical process was also applied to formulate the main starch carrier for theophylline (Szepes et al., 2008). The potato (PS) and maize (MS) starches containing theophylline were treated with 700 MPa for 5 min in order to evaluate (in vitro) their effectiveness in drug delivery behavior. The release mechanism of theophylline from the starch-based matrices was characterized with different empirical models. The mechanism that regulates the release behavior of an active substance from the polysaccharide matrices involves such complex processes as: swelling, wettability, diffusion, biodegradation (erosion) processes, and their interactions (Nair & Jyothi, 2013). According to Szepes and co-authors, the release of theophylline from PS best fitted to the Hixon–Crowel model indicating that the drug release occurred only in vertical direction relative to matrix surface. However, the release of theophylline from MS matrices was best explained by the Krosmeyer–Peppas kinetics signifying that the theophylline release was governed by non-Fickian diffusion. This phenomenon was ascribed by the authors to the simultaneous water uptake during drug diffusion, which in turn affected matrix relaxation.

Little information is available in literature regarding applicability of HP and use of other types of starch i.e. with unique physicochemical properties (amaranth and sorghum starches) (Błaszczak, Misharina, Fessas, Signorelli, & Gorecki, 2013), or starches with complex polymorph structure (Hylon VII) to obtain novel material with suitable properties for drug release.

In this study the following starches: waxy maize and amaranth starch (composed of almost 100% amylopectin), maize and sorghum (∼20% of amylose) as well as Hylon VII (68% of amylose), were evaluated as the main and potential carriers of theophylline. Theophylline as a model drug (at low and high drug content) was used to characterize drug delivery behavior from starch matrices prepared via hydrothermal (autoclaving, 121 °C, 0.1 MPa, 20 min) and non-thermal (HHP, 650 MPa, 9 min, 30 ± 2 °C) treatment. An in vitro study was conducted in order to determine kinetic parameters by fitting experimental data to selected mathematical models.