Influence of different viscosity grade cellulose-based polymers on the development of valsartan controlled release tablets

This work is based on formulating and optimizing controlled release (CR) valsartan (160 mg) tablets using different viscosity grades of the cellulosic polymer. The objective was to develop an effective once-daily drug delivery system of this cardiovascular agent. Central composite design was used for designing the formulations. Polymers used were Methocel® K4M, K15M and K100M. Compatibility of excipients with active was studied through FT-IR. Micromeritic properties were determined and formulations exhibiting appropriate flow characteristics were compressed. Swelling behavior and in vitro buoyancy effect were studied and response surface curves were constructed to optimize the formulation. Multi-point dissolution profiles of valsartan CR tablets at pH 1.2, 4.5 and 6.8 were obtained. Model-dependent and model-independent methods were performed including f2, stability test as per ICH guidelines and ANOVA. FT-IR studies revealed the compatibility of valsartan with all excipients. Formulation K4T9 (containing 25% K4M polymer) was selected to be the best optimized trial, based on physical properties and controlled release profile (23% at 4 h, 82% at 16 h and 100% at 24 h). Results of buoyancy and swelling behavior indicated that HPMC-K4M polymer exhibited excellent floating lag time and swelling indexes. In vitro drug release kinetics showed that formulation K4T9 displayed Korsmeyer–Peppas drug release pattern with r value > 0.99. The manufacturing process of K4T9 was also found to be reproducible with a shelf life period of 41 and 36 months at room temperature and accelerated conditions, respectively. Valsartan CR matrix-based formulation was successfully prepared with Methocel K4M retardant.     

Combined effect of high pressure treatment and anti-microbial bio-sourced materials on microorganisms' growth in model food during storage

Antimicrobial bio-sourced films based on poly(lactic acid) containing either carvacrol or allyl isothiocyanate (AITC) were prepared and their antimicrobial properties were assessed on Botrytis cinerea during storage and after a high pressure (HP) “pasteurisation-like” treatment (up to 800 MPa at ambient temperature). A dry process (extrusion + thermomoulding) was used to shape the material. The high temperature encountered during film processing dramatically decreased the carvacrol and AITC content in the film, leading to a less efficient antimicrobial activity. The use of β-cyclodextrin (β-CD) to encapsulate the active compounds before film processing proved to be efficient to protect the AITC against thermal degradation and to control its release from the films during its use. PLA-based films containing either AITC or β-CD encapsulated AITC showed a significant activity against B. cinerea. An effective combination between the antimicrobial activity of AITC-based films and the high pressure treatment was observed on a model food system (PDA) inoculated with N × 10⁴ (N ~ 1–9) conidia of B. cinerea. An HP treatment of only 300 MPa associated with an antimicrobial PLA/β-CD system providing an initial quantity of active agents equivalent to 4 mg of AITC/L of air (i.e. almost 2 folds lower than the minimal inhibition concentration of the active packaging used alone, which was determined to be equal to 10 mg/L of air in the same conditions) was found more efficient (total inhibition of B. cinerea growth during 10 days) than an 800 MPa HP treatment used alone (increase of the lag phase growth of 3.3 days).

Industrial relevance

The consumer demand for “fresh like” product containing reduced amount of preservatives without compromising human and environmental safety needs the development of new preservation strategies. As a consequence, the concept of “hurdle technologies” has risen up. The combined effect of HP treatment and volatile antimicrobial packaging allowed the use of lower individual treatment intensities to inhibit B. cinerea growth. Combining such “hurdles” is of relevance in the context of development of low-cost and eco-friendly food technologies.     

Price sensitive demand with random sales price – a newsboy problem

Up to now, many newsboy problems have been considered in the stochastic inventory literature. Some assume that stochastic demand is independent of selling price (p) and others consider the demand as a function of stochastic shock factor and deterministic sales price. This article introduces a price-dependent demand with stochastic selling price into the classical Newsboy problem. The proposed model analyses the expected average profit for a general distribution function of p and obtains an optimal order size. Finally, the model is discussed for various appropriate distribution functions of p and illustrated with numerical examples.     

Casein micelles as a vehicle for iron fortification of foods

Casein micelles were loaded with iron to create a dispersible delivery format for insoluble iron by exposing milk at chilled temperatures to a high concentration of soluble iron (up to 20 mmol kg⁻¹ ferrous and ferric chloride). The loading was maximised by applying a pH-cycle to the fortified milk by means of carbonation. Upon acidification of fortified milk, no release of iron was observed, except at the highest concentration. Changes in the buffering capacity as a function of pH confirmed the formation of colloidal iron phosphates. Overall, most properties of the micelles did not change: hydration, protein distribution between soluble and colloidal phase remained constant, but zeta potential decreased slightly and curd formation upon renneting became much slower. The renneting behaviour could be improved by carbonation or storage at 30 °C for a day. Iron-fortified milk samples were stable under heating, except when fortification was achieved by means of 20 mmol kg⁻¹ ferric chloride. The most obvious difference of iron-fortified milk is its appearance: samples fortified with ferrous chloride were darker than control, whereas samples fortified with ferric chloride were more red/yellow.     

Photocatalytic degradation of diclofenac using hybrid MIL-53(Al)@TiO2 and MIL-53(Al)@ZnO catalysts

In this work, TiO₂ and ZnO were incorporated successfully into a MIL-53(Al) metal–organic framework (MOF) to form nanocomposites via a facile post-modification technique. The hybrid MIL-53(Al)@TiO₂ and MIL-53(Al)@ZnO were characterized by several characterization tests. The X-ray diffraction (XRD), Fourier-transform infrared (FTIR), and field-emission scanning electron microscopy (FE-SEM) analyses showed evidence of the successful incorporation of TiO₂ and ZnO within the MIL-53(Al) framework. The thermal gravimetric analysis (TGA) analysis demonstrated the excellent thermal stability of MIL-53(Al)@TiO₂ and MIL-53(Al)@ZnO, while diffuse reflectance spectroscopy (DRS) determined the direct optical band gaps of MIL-53(Al)@ZnO and MIL-53(Al)@TiO₂ to be 3.24 and 3.34 eV, respectively. The composites were also tested for the photocatalytic degradation of diclofenac (DCF) as a micropollutant. The DCF degradation efficiency of the photocatalysts was ranked in the following order: MIL-53(Al)@TiO₂ > MIL-53(Al) > TiO₂ > ZnO > MIL-53(Al)@ZnO. The incorporation of TiO₂ enhanced the optical properties of MIL-53 (Al), which was confirmed with the superior photodegradation efficiency of MIL-53(Al)@TiO₂ (>85% in 2 h) as compared to the pristine MIL-53(Al) (around 80% in 2 h). The improvement in the photodegradation of the hybrid-MOF is mostly associated with the possible dual function of the adsorption and photodegradation mechanisms. The reusability of MIL-53(Al) and its composites was inspected over 3 cycles of photodegradation experiments with DCF. The photocatalytic activity of MIL-53(Al)@TiO₂ remained unchanged (>90%), while for MIL-53(Al) and MIL-53(Al)@ZnO a slight drop was observed over three cyclic degradation experiments. Fluorescence measurements revealed that the hydroxyl radical is an important reactive oxygen species produced by all the photocatalysts that aid in the photodegradation of DCF. Furthermore, the kinetic modelling of the photoreaction identified a second-order kinetics for all catalysts. Experiments with scavengers showed that hydroxyl radicals played a major role in the photocatalytic process, and it was found that only 2 h of treatment was sufficient to obtain a considerable chemical oxygen demand (COD) reduction of 58%.     

Morphological and palynological assessment of taxonomically problematic genus Paspalum based on light and scanning electron microscopy

Present research work was carried out to clarify the variations among species of genus Paspalum morphologically and palynologically as this genus is taxonomically difficult due to having multiple similar morphologically overlapping characters which make it difficult to identify. Henceforth present research work was carried out to delimit taxa within the same genus by morphological and palynological tools through light microscopy (LM) and scanning electron microscopy (SEM). Both these tools are considered as the most useful taxonomic characters for taxonomically problematic genera. The results showed a lot of variations among morphological characters. In Paspalum dilatatum, the upper glume was ovate whereas in the other two species, the upper glume was elliptic. The upper glume apex found in P. dilatatum and Paspalum scrobiculatum was obtuse whereas in Paspalum distichum, upper glume apex was acute. Glume nerves showed variation in all three species. Paspalum distichum was 3 nerved, P. scrobiculatum was 5–7 nerved, and P. dilatatum was 5–9 nerved. All three species showed variation in lemma nerves. Paspalum scrobiculatum had 3 nerved lemma whereas in P. distichum 3–5 nerved and P. dilatatum 5–9 nerved lemma were present. In polar and equatorial view, pollen grains ranged from 25 (20–30) to 37.5 (30–45) μm. Paspalum distichum appeared to be the smallest in size whereas P. dilatatum was the largest. Exine thickness ranged from 0.75 (0.5–1) to 1.35 (1.2–1.5) μm. The higher value of pollen fertility was found in P. scrobiculatum as 87.69% and the lowest value was in P. distichum as 78.08%. Morphological keys were also given for correct identification.     

Electroreductive block copolymerization of dichlorosilanes in the presence of disilane additives

The electroreductive polymerization of dichloromethylphenylsilane in the presence of triphenylsilyl group‐containing disilanes such as hexaphenyldisilane followed by the electroreductive termination with chlorotriphenylsilane afforded triphenylsilyl group‐terminated polymethylphenylsilane in 15–32% yield. The isolated polymethylphenylsilane (M_n = 3350 g mol^?1, M_w/M_n = 1.4) was found to react as a macroinitiator to copolymerize with dibutyldichlorosilane under electroreductive conditions producing the corresponding block copolymer (M_n = 4730 g mol^?1, M_w/M_n = 1.2) in 38% yield. The ratio of monomer units (? MeSiPh? to? BuSiBu? ) of the copolymer was determined to be 75:25 using ¹H NMR analysis, which was in good agreement with the calculated ratio (74:26) on the assumption that molecular weight of the macroinitiator was not changed. The block structure of the resulting copolymer, poly(methylphenylsilane)‐block‐poly(dibutylsilane), was also confirmed by comparing its ¹H NMR and UV absorption spectra with those of polymethylphenylsilane, polydibutylsilane and a statistical copolymer prepared by electroreductive polymerization of dichloromethylphenylsilane with dibutyldichlorosilane. This method is applicable to the preparation of other types of macroinitiator such as triphenylsilyl group‐terminated polydibutylsilane, and polydibutylsilane‐block‐polymethylphenylsilane was also obtained using this macroinitiator. Copyright © 2011 Society of Chemical Industry     

Poly(glycerol sebacate) nanoparticles for ocular delivery of sunitinib: physicochemical,cytotoxic and allergic studies

Poly(glycerol sebacate) (PGS) is a new biodegradable polymer with good biocompatibility used in many fields of biomedicine and drug delivery. Sunitinib‐loaded PGS/gelatine nanoparticles were prepared by the de‐solvation method for retinal delivery and treatment of diabetic retinopathy. The nanoparticles were characterised by Fourier‐transform infrared and differential scanning calorimetry. The effects of different formulation variables including drug‐to‐carrier ratio, gelatine‐to‐PGS ratio, and glycerine‐to‐sebacate ratio were assessed on the encapsulation efficiency (EE%), particle size, release efficiency (RE), and zeta potential of the nanoparticles. The in vitro cytotoxicity of PGS/gelatine nanoparticles was studied on L929 cells. Draize test on rabbit eyes was also done to investigate the possible allergic reactions caused by the polymer. Glycerine/sebacic acid was the most effective parameter on the EE and RE. Gelatine‐to‐PGS ratio had the most considerable effect on the particle size while the RE was more affected by the glycerine/sebacic acid ratio. The optimised formulation (S₁ G_0.7 D_21.2) exhibited a particle size of 282 nm, 34.6% EE, zeta potential of −8.9 mV, and RE% of about 27.3% for drug over 228 h. The 3‐(4,5‐dimethylthuazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay indicated PGS/gelatine nanoparticles were not cytotoxic and sunitinib‐loaded nanoparticles were not toxic at concentrations <36 nM.Inspec keywords: polymers, differential scanning calorimetry, toxicology, drug delivery systems, solvation, eye, encapsulation, particle size, drugs, biodegradable materials, nanofabrication, nanomedicine, nanoparticles, gelatin, Fourier transform infrared spectraOther keywords: gelatine‐to‐PGS ratio, glycerine‐to‐sebacate ratio, particle size, zeta potential, sunitinib‐loaded nanoparticles, biodegradable polymer, retinal delivery, differential scanning calorimetry, drug‐to‐carrier ratio, allergic reactions, physicochemistry, cytotoxicity, poly(glycerol sebacate) nanoparticles, sunitinib ocular delivery, drug delivery, sunitinib‐loaded PGS‐gelatine nanoparticles, Fourier‐transform, in vitro cytotoxicity, biocompatibility, Draize test, rabbit eyes, 3‐(4,5‐dimethylthuazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay