Ashok R. Patel

Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate

The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.

Sodium caseinate stabilized zein colloidal particles.

The present work deals with the preparation and stabilization of zein colloidal particles using sodium caseinate as electrosteric stabilizer. Colloidal particles with well-defined size range (120-150 nm) and negative surface potential (-29 to -47 mV) were obtained using a simple antisolvent precipitation method. Due to the presence of caseinate, the stabilized colloidal particles showed a shift of isoelectric point (IEP) from 6.0 to around pH 5.0 and thus prevent the aggregation of zein near its native IEP (pH 6.2). The particles also showed good stability to varying ionic strength (15 mM-1.5 M NaCl). Furthermore, stabilized particles retained the property of redispersibility after drying. In vitro protein hydrolysis study confirmed that the presence of caseinate did not alter the digestibility of zein. Such colloidal particles could potentially serve as all-natural delivery systems for bioactive molecules in food, pharmaceutical, and agricultural formulations.

Quercetin loaded biopolymeric colloidal particles prepared by simultaneous precipitation of quercetin with hydrophobic protein in aqueous medium

Quercetin loaded biopolymeric colloidal particles were prepared by precipitating quercetin (water insoluble polyphenol) and zein (hydrophobic protein), simultaneously, by adding their hydro-alcoholic solution to aqueous solution in presence of sodium caseinate as an electrosteric stabiliser. The presence of protein resulted in altering the shape of quercetin precipitates from needle-like to spherical shape at higher zein proportions, as confirmed by transmission electron microscopy. The average particle size of zein:quercetin composite particles was below 200 nm (130-161 nm) with negative surface charge (-30 to -41 mV), as confirmed by dynamic light scattering and electrophoretic mobility data. Solid state characterisation (X-ray diffraction) and spectroscopic measurements (UV-Vis and IR spectroscopy) confirmed characteristic changes in quercetin due to the entrapment in the biopolymeric matrix of colloidal particles. Results from anti-oxidant study demonstrated the advantage of entrapping quercetin in the colloidal particles in terms of the chemical stability in the alkaline pH and against photodegradation under UV-light irradiation.

Edible oil structuring: an overview and recent updates

In recent years, research dealing with edible oil structuring has received considerable interest from scientific community working in the area of food formulation. Much of this interest is linked to the possibility of using structured oil in development of newer product formats with improved nutritional profile (trans fat-free, low in saturated fats and high in mono and/or poly unsaturated fatty acids). In addition to the obvious industrial need of finding the alternative formulation approach, the interesting properties of structured systems (particularly, oleogels) also makes them a fascinating subject for fundamental studies. In this paper, we attempt to give a comprehensive and concise overview of the field of oil structuring with special emphasis on the updates from recent years. Specifically, several categories of food-grade oleogelators and their potential food applications are summarized with typical examples along with a discussion on the general principles and unresolved challenges related to this emerging area.

Preparation and rheological characterization of shellac oleogels and oleogel-based emulsions.

We report the preparation and rheological characterization of oleogels and oleogel-based emulsions prepared using shellac as a structurant. Shellac showed excellent oleogelation properties, resulting in liquid oil gelation at a concentration as low as 2 wt%. Microscopic evaluation of these oleogels indicated that the oil gelation was a result of physical entrapment of liquid oil in crystal networks of shellac formed by cooling the hot oil dispersions of shellac to room temperature. The rheological behaviour of shellac oleogels to varying deformation (% strain) was comparable to oleogels prepared using a commercial crystal starter. The cooling and shear rate showed a significant effects on the rheological properties of formed oleogels. The thermo-reversible, hysteresis, thixotropic and shear thinning properties of oleogels were evaluated by comparing rheological data obtained from rotational and oscillatory measurements. Shellac oleogels were further used as continuous phases to generate emulsifier-free w/o emulsions which surprisingly showed good stability over 4 months of storage. Microscopy and rheological evaluations of these emulsions were carried out to obtain more insight into its microstructures.

A foam-templated approach for fabricating organogels using a water-soluble polymer

We report a unique approach of using a water soluble polymer (a cellulose derivative) to generate organogels via a facile, low temperature process. This finding is an important step towards the development of liquid oil-based soft matter systems for applications in non-bio and bio-related fields.

Biopolymer-based structuring of liquid oil into soft solids and oleogels using water-continuous emulsions as templates.

Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble biopolymers was achieved using a facile two-step process by first formulating a surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a polysaccharide) followed by complete removal of the water phase (by either high- or low-temperature drying of the emulsion) resulting in structured solid systems containing a high concentration of liquid oil (above 97 wt %). The microstructure of these systems was revealed by confocal and cryo-scanning electron microscopy, and the effect of biopolymer concentrations on the consistency of emulsions as well as the dried product was evaluated using a combination of small-amplitude oscillatory shear rheometry and large deformation fracture studies. The oleogel prepared by shearing the dried product showed a high gel strength as well as a certain degree of thixotropic recovery even at high temperatures. Moreover, the reversibility of the process was demonstrated by shearing the dried product in the presence of water to obtain reconstituted emulsions with rheological properties comparable to those of the fresh emulsion.

Shellac as a natural material to structure a liquid oil-based thermo reversible soft matter system

We demonstrate the novel use of shellac as a natural material to structure liquid oil into an oleogel. Thermo reversible oleogels with different texture, gel strength and temperature behaviour could be obtained by altering the concentration of shellac. Further, a possible application of shellac oleogel in the preparation of w/o spreadable emulsions is described.

Colloidal complexation of a macromolecule with a small molecular weight natural polyphenol: implications in modulating polymer functionalities

Natural polyphenolic compounds show interesting complexation behavior with various macromolecules due to their unique structural characteristics that enables molecular transition such as electronic delocalization and conjugation and intra- and intermolecular hydrogen bonding. Here, we report on the preparation and characterization of novel colloidal complexes (size range of 56–116 nm) based on the spontaneous interactions of a small molecular weight polyphenol (tannic acid) with an industrially relevant macromolecule (methylcellulose). The binding stoichiometry obtained from isothermal titration calorimetry suggested that 33 molecules of tannic acid were bound to one molecule of polymer. The values of ΔH (−11.4 kJ mol−1) and ΔS (−35.5 J K−1 mol−1) suggested that the interaction was enthalpy driven and the relatively low value of ΔH further indicated the non-covalent nature (i.e. hydrophobic interaction and hydrogen bonding) of the interaction. Effects of this complexation on the functionalities of methylcellulose were investigated in terms of the loss of thermoreversible gelling (due to the irreversible association of colloidal complexes at high temperature), improvement of the emulsifying property (because of the interfacial localization of hydrophobic colloidal complexes further contributing to the gelling of the interfacial film) and enhancement of the foam stabilizing property (based on the absorption of colloidal complexes on the air–water interface and resulting enhancement of the interfacial stiffness due to surface gelation invoked by the colloidal complexes). These findings will be of wide interest to researchers and industrial scientists working in the field of polymer chemistry and material science, especially because methylcellulose is one of the most commonly used polymers for a range of industrial applications.

Comparative evaluation of structured oil systems : shellac oleogel, HPMC oleogel, and HIPE gel

In lipid-based food products, fat crystals are used as building blocks for creating a crystalline network that can trap liquid oil into a 3D gel-like structure which in turn is responsible for the desirable mouth feel and texture properties of the food products. However, the recent ban on the use of trans-fat in the US, coupled with the increasing concerns about the negative health effects of saturated fat consumption, has resulted in an increased interest in the area of identifying alternative ways of structuring edible oils using non-fat-based building blocks. In this paper, we give a brief account of three alternative approaches where oil structuring was carried out using wax crystals (shellac), polymer strands (hydrophilic cellulose derivative), and emulsion droplets as structurants. These building blocks resulted in three different types of oleogels that showed distinct rheological properties and temperature functionalities. The three approaches are compared in terms of the preparation process (ease of processing), properties of the formed systems (microstructure, rheological gel strength, temperature response, effect of water incorporation, and thixotropic recovery), functionality, and associated limitations of the structured systems. The comparative evaluation is made such that the new researchers starting their work in the area of oil structuring can use this discussion as a general guideline. Practical applications Various aspects of oil binding for three different building blocks were studied in this work. The practical significance of this study includes (i) information on the preparation process and the concentrations of structuring agents required for efficient gelation and (ii) information on the behavior of oleogels to temperature, applied shear, and presence of water. This information can be very useful for selecting the type of structuring agents keeping the final applications in mind. For detailed information on the actual edible applications (bakery, chocolate, and spreads) which are based on the oleogel systems described in this manuscript, the readers are advised to refer our recent papers published elsewhere. (Food & Function 2014, 5, 645–652 and Food & Function 2014, 5, 2833–2841).