Drug release from calcium and zinc pectinate beads: Impact of dissolution medium composition

The aim of this study was to investigate drug release from calcium and zinc pectinate beads and to understand the impact of medium electrolytes during drug transfer. A potential drug carrier for colonic drug delivery (rutin) was prepared with calcium and zinc pectinate beads and was tested in three different simulated intestinal fluids (pH 7.3) with phosphates (Sorensen’s and Mc Ilvaine’s buffers) and without phosphates (Tris-buffer). According to swelling studies and zinc ions release, it was showed that zinc ions keep adhering to the bead surface. Drug release and swelling behaviour from the two dosage forms depend not only on pH and ionic strength but also on the electrolytes there were …

Dry adsorbed emulsion: 2. Dissolution behaviour of an intricate formulation

The behaviour of a pharmaceutical form, called dry adsorbed emulsion (DAE), containing a sparingly soluble drug (i.e. theophylline) was studied for dissolution drug release kinetic, in relation with DAE structure characterisation. In vitro dissolution testings were performed under different experimental conditions (medium at pH 1.2 and 7.4, medium with or without surfactant addition, different particle sizes, discrete or densified particles). Discrete DAE particles showed an extended release, in comparison with the native drug powder, depending on both drug solubility in the medium and particle size. The relevance of dissolution data was not improved by surfactant addition (0.1% sodium laur…

Silica-coated calcium pectinate beads for colonic drug delivery

The aim of this work is to develop novel organic-inorganic hybrid beads for colonic drug delivery. For this purpose, calcium pectinate beads with theophylline are prepared by a cross-linking reaction between amidated low-methoxyl pectin and calcium ions. The beads are then covered with silica, starting from tetraethyoxysilane (TEOS), by a sol-gel process. The influence of TEOS concentration (0.25, 0.50, 0.75 and 1.00 M) during the process is studied in order to modulate the thickness of the silica layer around the pectinate beads and thus to control the drug release. The interactions between the silica coating and the organic beads are weak according to the physicochemical characterizations…

Dry adsorbed emulsion: 1. Characterization of an intricate physicochemical structure

Abstract A recent solid pharmaceutical form called “Dry Adsorbed Emulsion” (DAE) was characterized in morphological and structural fields. A DAE is an intricate system initiated by a water‐in‐oil emulsion including the active drug (i.e., theophylline). Each emulsion phase is adsorbed on pulverulent adsorbents with a suitable polarity (silica) to obtain a free‐flowing powder with nonporous particles of size from 125 to 710 μm, with small specific surface area and a spherical shape. Different methods, such as scanning electron microscopy combined with chemical microanalysis, dying tests, and electron spin resonance studies, allow the formulator to follow the behavior of DAE aqueous and oily p…

Colonic drug delivery: influence of cross-linking agent on pectin beads properties and role of the shell capsule type.

For colonic delivery, pectin beads obtained by ionotropic gelation method have been already reported as an interesting approach. This study investigated the influence of the cross-linking agent (calcium or zinc) and the type of shell capsule used (classical or enteric capsules) on pectin beads properties and on their performance to target the colon (in vitro dissolution studies with subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate beads seemed to be relatively similar to calcium's ones in morphological point, except on the surface aspect. When beads were introduced in classical hard capsules, ketoprofen release was not significantly different between CPG and ZP…

Corrigendum to “Influence of temperature and NaCl on the release in aqueous liquid media of aroma compounds encapsulated in edible films” [Journal of Food Engineering 108 (2012) 30–36]

Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were…

Influence of drug polarity upon the solid-state structure and release properties of self-emulsifying drug delivery systems in relation with water affinity.

To overcome low oral bioavailability of poorly water-soluble drugs, self-emulsifying drug delivery systems (SEDDS) have been noted as a promising strategy. However, incorporation of drugs into SEDDS composed of Gelucire44/14 could induce interactions not yet well understood. The aim of this study was to investigate the influence of drug polarity upon the solid-state structure of SEDDS formulation, particularly in terms of wettability, thermal behaviour and microscopic aspects and their effect upon the release properties of the SEDDS. Model drugs were naproxen and sodium naproxen (10% w/w), two drugs with similar chemical structure but different water solubilities. Both drugs had an effect o…

Renouvellement d’une ordonnance anti-acnéique

Une jeune fille de 19 ans se presente a l’officine pour le renouvellement de son ordonnance mensuelle dans le cadre de la prise en charge d’une acne papulo-pustuleuse.

Influence of cryogenic grinding on properties of a self-emulsifying formulation

Abstract Recently, self-emulsifying drug delivery systems (SEDDS) have been developed as a method to deliver lipophilic drugs. Gelucire® 44/14 is an excipient, from the lauroyl macrogolglycerides family, producing a fine oil-in-water emulsion when introduced into an aqueous phase under gentle agitation as SEDDS, improving thereby solubility of poorly water-soluble drugs and their bioavailability. The aims of this study were to process Gelucire® 44/14 into a powder by cryogenic grinding to produce solid oral dosage forms and to investigate influence of this process on different properties of a formulation made of Gelucire® 44/14 and ketoprofen (90/10). Cryogenic grinding produced Gelucire® 4…

Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol® ATO 5

Abstract Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ® ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol ® ) included in lipid matrices composed of glyceryl palmitostearate (Precirol ® ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline relea…

A way to follow the viability of encapsulated Bifidobacterium bifidum subjected to a freeze-drying process in order to target the colon: Interest of flow cytometry

The aim of this work was to apply flow cytometry in order to assess and compare the viability of freeze-dried entrapped bacteria with an usual technique by quantification by plate count techniques. It also aimed at studying the effect of various cryoprotectants on the viability of an entrapped Bifidobacterium bifidum subjected to freeze-drying to check their ability to be delivered all along the gastro-intestinal tract. The alginate-pectinate beads were chosen as the encapsulation matrix added with different protectants. The beads were characterized by scanning electron microscopy and the viability was checked by both methods. The best combination to improve viability of entrapped bacteria …

Applications of spray-drying in microencapsulation of food ingredients: An overview

International audience; Spray-drying process has been used for decades to encapsulate food ingredients such as flavors, lipids, and carotenoids. During this drying process, the evaporation of solvent, that is most often water, is rapid and the entrapment of the interest compound occurs quasi-instantaneously. This required property imposes a strict screening of the encapsulating materials to be used in addition to an optimization of the operating conditions. Likewise, if the encapsulated compound is of hydrophobic nature, the stability of the feed emulsion before drying should also be considered. Thus, spray-drying microencapsulation process must rather be considered as an art than a science…

Effect of high methoxyl pectin on pea protein in aqueous solution and at oil/water interface

International audience; The effect of the addition of high methoxyl pectin on the stability of pea protein isolate emulsions was investigated. Except for low pectin concentrations at acidic pHs where bridging flocculation occurred the addition of pectin improved emulsion stability to pH changes and depletion flocculation induced by maltodextrin addition. The mechanism of pectin induced stability was probed by measuring protein-pectin complex formation in solution, zeta potential of the emulsions droplets and the change in surface viscoelasticity on pectin addition. The phase diagrams of pectin-pea protein isolate in solution and pectin-pea protein-stabilized emulsions were established based…

Phytochemical analysis of two Weigela florida cultivars, “Pink Poppet” and “Jean’s Gold”

Abstract Nine different oleanane-type glycosides were extracted and isolated by various chromatographic methods from two Weigela florida cultivars, “Pink Poppet” and “Jean’s Gold”. From the roots of W. florida “Pink Poppet”, three monodesmosidic oleanolic acid saponins 1, 4, 5 were obtained, together with one hederagenin ester 6 from the leaves, and six bidesmosidic saponins 2, 3, 6-9 were isolated from the leaves of W. florida “Jean’s Gold”. Among compounds 1-9, three were previously undescribed (1-3) and six (4-9) were already published in the literature. Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESI-MS). The cytotoxicity of the isolated…

Solutions, suspensions et émulsions destinées aux voies orale, parentérale et ophtalmique

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Une jeune femme atteinte d’un psoriasis

Une jeune femme âgee de 24 ans se presente a l’officine pour le renouvellement mensuel de son ordonnance dans le cadre de la prise en charge d’un psoriasis evoluant depuis 15 mois. A cette occasion, la gestion de ce traitement symptomatique et notamment les precautions relatives a son application doivent etre expliquees. Le rappel de quelques conseils hygieno-dietetiques complete l’acte de delivrance.

Physico-chemical state influences in vitro release profile of curcumin from pectin beads

International audience; Curcumin is a polyphenolic compound with diverse effects interesting to develop health benefit products but its formulation in functional foods or in food supplement is hampered by its poor water solubility and susceptibility to alkaline conditions, light, oxidation and heat. Encapsulation of curcumin could be a mean to overcome these difficulties. In this paper, curcumin was encapsulated by ionotropic gelation method in low methoxyl pectin beads associated with different surfactants: Solutol®, Transcutol® and sodium caseinate. After encapsulation, physico-chemical properties of encapsulated curcumin such as its solubility, physical state, tautomeric forms and encaps…

Structure of calcium and zinc pectinate films investigated by FTIR spectroscopy

International audience; Calcium and zinc pectinate gels were prepared using a method which allowed calcium or zinc to diffuse from the cross-linking solution through a dialysis membrane to form a gel with amidated low-methoxyl pectin. The gel thus obtained was then dried, and the film structure was studied using FTIR spectroscopy as a function of the cation content (0%, 5%, 10%, and 15% w/v). Important consideration was given to the three functional groups (amide, carboxyl ester, and carboxylate groups) present in the pectin. When the zinc content was increased, the three wavenumber values corresponding to these three functional groups did not change significantly, while for calcium pectina…

Cytotoxic glycosides from the roots of Weigela x “Bristol Ruby”

International audience; Seven oleanane-type glycosides were extracted and isolated by various chromatographic methods from the roots of Weigela x "Bristol Ruby" (1-7), six previously undescribed (1-6) and a known one (7). Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESIMS). Selected triterpenoid glycosides (1-3, 6, 7) displayed a good cytotoxic activity against a mouse colon cancer cell line CT26.

Controlled release of tyrosol and ferulic acid encapsulated in chitosan–gelatin films after electron beam irradiation

Abstract This work deals with the study of the release kinetics of antioxidants (ferulic acid and tyrosol) incorporated into chitosan–gelatin edible films after irradiation processes. The aim was to determine the influence of electron beam irradiation (at 60 kGy) on the retention of antioxidants in the film, their release in water (pH=7) at 25 °C, in relation with the barrier and mechanical properties of biopolymer films. The film preparation process coupled to the irradiation induced a loss of about 20% of tyrosol but did not affect the ferulic acid content. However, 27% of the ferulic acid remained entrapped in the biopolymer network during the release experiments whereas all tyrosol was …

Colon-specific drug delivery: Influence of solution reticulation properties upon pectin beads performance.

In this study, pectinate gel beads were produced by ionotropic gelation method with different solutions of cross-linking agents and ketoprofen was entrapped as model drug. The influence of these formulation parameters was investigated upon bead properties and upon their performance to target the colon. Zinc pectinate beads obtained with 10% of counter-ions solution at pH 1.6 exhibited the strongest gel network due to "egg-box" dimmer formation helped by hydrogen bonding. Furthermore the gel network formed at low pH was arranged in a compact three-fold conformation. Thus, this matrix structure in enteric capsules induced the lowest drug release in the upper gastro-intestinal tract (pH 1.2 fo…

Performance of Multilayered Particles: Influence of a Thin Cushioning Layer

Nowadays, oral dosage forms with controlled release kinetics have known an increasing interest. The polymer coating of drug-loaded particles is one of the most common methods used for controlling drug delivery. Such multilayered particles could be either filled into capsules or compressed into tablets for their oral administration. However, many studies have noticed that coating films are damaged during the compression process, leading to significant changes in drug release profiles. The aims of this study were to investigate the effects of a thin cushioning layer [made of HydroxyPropylMethyl Cellulose (HPMC)] applied on coated theophylline particles upon particle characteristics, tablet pr…

Influence of temperature and NaCl on the release in aqueous liquid media of aroma compounds encapsulated in edible films

This work analyses the release of n-hexanal and D-limonene from edible films, previously encapsulated in the iota-carrageenan matrix (with and without lipid). Both volatile compounds have different physicochemical properties. The effect of temperature (25 degrees C and 37 degrees C) and dissolution medium (water and 0.9% NaCl) on the release and retention of aroma compounds were studied. Hydrophobicity and wettability properties of active iota-carrageenan films were also studied and they were related with the internal and surface microstructure of films. Results highlight that D-limonene is encapsulated in the lipid phase of the films decreasing the release in the salt medium. D-limonene, t…

Steroidal glycosides from the Vietnamese cultivar Cordyline fruticosa “Fairchild red”

Abstract A phytochemical study of Cordyline fruticosa “Fairchild red” (Asparagaceae) from Vietnam, led to the isolation of fourteen steroidal glycosides, including twelve previously undescribed along with two known ones. Ten compounds were obtained by successive solid/liquid chromatographic methods from an aqueous-ethanolic extract of the roots, and four from the aerial parts. Their structures were elucidated mainly by spectroscopic analysis 2D NMR and mass spectroscopy (ESI-MS), as spirostanol glycosides, 5α-spirost-25(27)-ene-1β,3β,4α-triol 1-O-β-D-fucopyranoside, 5α-spirost-(25)27-ene-1β,3β,4α-triol 1-O-β-D-xylopyranoside, 5α-spirost-(25)27-ene-1β,3β,4α-triol 1-O-α-L-rhamnopyranosyl-(1 →…

Preformulation: Effect of Moisture Content on Microcrystalline Cellulose (Avicel PH-302) and Its Consequences on Packing Performances

This study evaluates the influence of moisture content on the packing performances of a new grade of microcrystalline cellulose (MCC) (Avicel PH-302) either by classical method or by an unconventional compression technique (constant volume reduction of powder bed). An increase in moisture content decreases the apparent density of the powder bed, resulting from interparticulate friction enhancement. This modification of apparent density seems to be the main effect caused by the presence of humidity, which explains the variations of compression properties, like an increase of powder plasticity generally observed in the experimental conditions.

Optimized tableting for extremely oxygen-sensitive probiotics using direct compression

International audience; Faecalibacterium prausnitzii was previously recognized for its intestinal anti-inflammatory activities and it has been shown less abundant in patients with chronic intestinal diseases. However, the main problems encountered in the use of this interesting anaerobic microorganism are firstly its high sensitivity to the oxygen and secondly, its ability to reach the large intestine alive as targeted site. The aim of this study was to investigate the effect of direct compression on the viability of this probiotic strain after different compression pressure and storage using three different excipients (MCC, HPMC and HPMCP). The effect of compression process on cell viabili…

Utilisation of pectin coating to enhance spray-dry stability of pea protein-stabilised oil-in-water emulsions

International audience; In this study, development of pea (Pisum sativum) protein stabilised dry and reconstituted emulsions is presented. Dry emulsions were prepared by spray-drying liquid emulsions in a laboratory spray-dryer. The effect of drying on the physical stability of oil-in-water emulsions containing pea protein-coated and pea protein/pectin-coated oil droplets has been studied. Oil-in-water emulsions (5 wt.% Miglyol 812 N, 0.25 wt.% pea protein, 11% maltodextrin, pH 2.4) were prepared that contained 0 (primary emulsion) or 0.2 wt.% pectin (secondary emulsion). The emulsions were then subjected to spray-drying and reconstitution (pH 2.4). The stability of the emulsions to dry pro…

The impact of whey protein preheating on the properties of emulsion gel bead

Thermal treatment effect (70 or 80 °C for 5 or 30 min) was evaluated on functional properties of whey protein isolate (WPI) dispersions used for the development of novel vitamin A delivery systems based on emulsion gel beads. This process combines an (O/W) emulsion diluted by a polysaccharide solution and a cold-set gelation induced by salt addition. Pre-heated WPI had a significant impact on the denaturation degree and on the surface hydrophobicity, respectively studied by differential scanning calorimetry and fluorescence. Stronger heating conditions (i.e. duration or temperature) induced complete denaturation, an increase of surface hydrophobicity and of viscosity. Under these conditions…

Structural behaviour differences in low methoxy pectin solutions in the presence of divalent cations (Ca 2+ and Zn 2+ ): a process driven by the binding mechanism of the cation with the galacturonate unit

International audience; In this paper, we compare the interactions between low methoxy pectin (LMP) and either Ca2+ or Zn2+ in semi-dilute solutions. Intrinsic viscosity and turbidity measurements reveal that pectin-calcium solutions are more viscous, but yet less turbid, than pectin-zinc ones. To get a molecular understanding on the origin of this rather unexpected behavior, we further performed isothermal titration calorimetry, small angle neutron scattering experiments, as well as molecular dynamics simulations. Our results suggest that calcium cations induce the formation of a more homogeneous network of pectin than zinc cations do. The molecular dynamics simulations indicate that this …

Properties of spray-dried food flavours microencapsulated with two-layered membranes: Roles of interfacial interactions and water

International audience; Engineering the interface of oil-in-water emulsion droplets with biopolymers that modify its permeability could provide a novel technique to improve flavour retention in dry powders. The objective of this study was to determine if volatile compounds were more retained in dry emulsions stabilized by pea protein isolate (PPI)/pectin complex than that stabilized by PPI alone. The retention of ethyl esters during spray-drying increased with decreasing volatility of the encapsulated compound and ranged from 28% to 40%. The addition of pectin to feed emulsions was quite effective in markedly improving the retention of the three studied flavour compounds. In our previous wo…

Pellets based on polyuronates: Relationship between gelation and release properties

International audience; Three polyuronates: amidated low methoxyl pectin (ALMP), low methoxyl pectin (LMP) and polygalacturonic acid (PGA) were used to encapsulate rutin in pellets, and they were characterized by different techniques (macroscopic properties, Calcium and rutin release). The ability of the three polyuronates to bind calcium ions and the viscoelastic properties of gels were performed to relate the properties of the pellets to the gel structures. The pellets size, the water content, the water uptake, the release of calcium and rutin varied depending on the polyuronate used. The pellets size of ALMP were smaller than LMP and PGA with a lower water content, but this matrix was mo…

Influence of low methoxyl pectin gel textures and in vitro release of rutin from calcium pectinate beads.

This study described the preparation and characterization of low methoxyl pectin (LMP) gels and beads for controlled release applications. The rheological characterization of the various formulations was proposed. Then the mechanical and morphological characterizations of beads were determined. Finally, the controlled release studies taking rutin as a model drug was evaluated. The results showed that Young's modulus values of non-amidated LMP gels decrease when adding up to 15% sorbitol. Calcium pectinate beads loaded with rutin are about 600 μm, oblong shaped with dense matrix. Beads containing sodium bicarbonate showed about 80% lower rutin encapsulation efficiency by increasing the pH of…

Pectin as Drug-Release Vehicle

Pectin as a natural biopolymer is extensively used for pharmaceutical and biomedical applications, essentially due to its gelling properties that could be influenced by pectin sources and extraction methods. This chapter focuses on an overview of pectin drug delivery systems classified by their administration routes. Oral drug delivery systems have been mainly developed, as pectin could be used in tablets as binder or matrix excipients and in microparticles/beads obtained by ionotropic gelation. The main objective is to target the colon, as pectin is resistant in acidic pH and sensitive to pectinolytic enzymes in the colon. To obtain suitable properties, pectin could be used in its native s…