Biomedical subjects

J L Grossiord

Publications and source records attributed to J L Grossiord.

17 recordsLinked to original sources

PubMed2005

Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine.

The aim of this work was to formulate and characterize thermosensitive gels based on poloxamer 407, a thermosensitive polymer, and hydroxypropylmethylcellulose (HPMC), a bioadhesive polymer, intended for the rectal delivery of quinine in children. In order to avoid the macroscopic phase separation between the two polymers it was necessary to add propanediol-1,2. After the formulation of stable ternary systems, their rheological properties were studied as a function of temperature. It was thus possible to obtained the gelation temperature of the systems as well as their elastic modulus, G', at 37 degrees C. It appeared that HPMC in the presence of propanediol-1,2 had a synergistic effect on the gelation of poloxamer 407. Tests on the rabbit rectal mucous membrane, founded on a technique of traction of the adhesive/adhered joint, made it possible to characterize the bioadhesive properties of the gels by measuring the work of adhesion, W, and the maximum detachment force, F(max). Over small concentration ranges of poloxamer and HPMC, very important variations of the viscoelastic and mucoadhesives properties were observed. It was shown that the viscoelastic and the bioadhesive properties were tightly correlated. Indeed, an empirical equivalence relation was established between the shear frequency and the rate of deformation in traction and allowed to describe all our samples by a master curve. This master curve would make it possible to predict the values of W at various rates of traction by the simple non-destructive measurement of the elastic modulus, G', at an equivalent shear frequency.

Adhesiveness↗

PubMed2005

Study of mass transfer in oil-water-oil multiple emulsions by differential scanning calorimetry.

A multiple emulsion of the type O1/W/O2 is studied experimentally by means of differential scanning calorimetry (DSC). The aim of this work is to characterize and measure the time-dependent changes within the emulsion. In particular, interest is focused to quantify the concentration changes in the internal and external phases of the O1/W/O2 multiple emulsion. In order to accomplish the objective, the measurement and analysis carried out by DSC are based on the crystallization behavior of the emulsion. A volume of a few mm3 is periodically removed from the O1/W/O2 multiple emulsion. The sample is submitted to steady cooling and the crystallization thermogram is recorded. The experimental data provided by the crystallization thermogram makes it possible to quantify the crystallized mass for both phases, the internal and the external. In addition, the composition in each phase can also be deduced from the thermogram. To deduce the composition, a diagram of crystallization temperatures is elaborated, employing several mixtures of known composition. In addition to the main objective previously mentioned, the influence of formulation parameters such as surfactant concentration in the aqueous phase and the mass ratio of the internal and external phases are also analyzed. The experimental results made it possible to conclude that a mass transfer took place from the internal phase toward the external phase; this transfer is caused by the composition difference on both sides of the aqueous membrane. In this work we analyzed the mass transfer in the multiple emulsion carried out by a composition gradient through the aqueous membrane. The most likely mechanism of mass transfer through the aqueous membrane is a solution-diffusion of tetradecane enhanced by the micelles of the surfactant Tween 20. The model of mass transfer confirms that the osmotic pressure difference controls the kinetics of tetradecane transfer. It is also confirmed that an increment of surfactant concentration in the aqueous phase allows a faster kinetics of the tetradecane transfer.

Journal Article↗

PubMed2005

Rheological properties of three different vitamin D ointments and their clinical perception by patients with mild to moderate psoriasis.

BACKGROUND: Ointments, classically used for the treatment of dermatological diseases, are monophasic viscous semisolid formulations. According to the proportion of their compounds, they have physicochemical and organoleptic properties and when applied on skin show a specific behaviour allowing to be spread more or less easily. OBJECTIVE: To measure in vitro rheological characteristics of three vitamin D derivative ointments prescribed for the treatment of psoriasis, and to compare their viscosity and clinical acceptability when applied on the diseased skin. METHODS: Rheological characteristics of tacalcitol 4 microg/g, calcipotriol 50 microg/g and calcitriol 3 microg/g ointments were assessed by measuring the oscillatory viscoelastic parameters and the permanent flow analysis. Clinical acceptability was studied in 20 psoriatic male or female subjects, aged 18 years or older. A survey evaluated the acceptability of calcitriol vs. tacalcitol and calcipotriol. Questions included information about fluidity, spreading capacity and stickiness after application. RESULTS: We demonstrated that viscoelastic parameters were four times higher for ointment tacalcitol than for calcipotriol and calcitriol, corresponding to a higher consistency of ointment tacalcitol compared to calcipotriol and calcitriol showing both similar results; better fluidity was demonstrated by calcitriol than by tacalcitol and calcipotriol. Comparable results were obtained for the quality to be spread. The sensation of stickiness, significantly different between tacalcitol and calcitriol, was not different between calcipotriol and calcitriol. CONCLUSION: The above results confirm the relationship between rheological in vitro and sensorial in vivo results: variations between different formulations may have an important influence on non-adherence and treatment failure.

Administration, Cutaneous↗

PubMed2002

In vitro microbicidal activity of W/O/W multiple emulsion for vaginal administration.

The microbicidal activity of a W/O/W multiple emulsion destined for vaginal application, containing lactic acid in the internal aqueous phase, octadecylamine (ODA) in the oily phase and benzalkonium chloride (CBZ) in the external aqueous phase was evaluated against three microbial strains: Escherichia coli, Staphylococcus aureus and Candida albicans. The results were different depending on the procedure used. Interpretable results were obtained if only a gentle agitation was used just after the introduction of the microbial suspension to the product. This suggested that vigorous agitation lead to a variable fraction of CBZ or ODA entrapped in the micelles of ethylene and propylene oxide copolymer (COE).

Administration, Intravaginal↗

PubMed2002

Water state characterization, swelling behavior, thermal and mechanical properties of chitosan based networks.

Two kinds of chitosan-based hydrogels, a crosslinked chitosan reference gel and a chitosan-poly(ethylene oxide) semi-interpenetrating network (semi-IPN), with potential pH-sensitive swelling and drug delivery properties are characterized. Swelling studies were performed on the two kinds of hydrogels by differential scanning calorimetry (DSC) at pH 1.2 and by the gravimetric method at pH 1.2 and pH 7.2. Both methods lead to similar results. If pH-dependent swelling properties were observed with both hydrogels, they were however improved for the semi-IPN. The amount of bound water in the xerogels could be determined from DSC measurements and a thermogravimetric analysis. The results obtained by both techniques were in good agreement and indicated that the semi-IPN contained more bound water than the reference gel probably due to the presence of the hydrophilic poly(ethylene oxide) chains. Young modulus of the swollen hydrogels was determined by indentation analysis. The semi-IPN displayed improved mechanical properties compared to the reference gel.

Calorimetry, Differential Scanning↗

PubMed2001

pH compartmented w/o/w multiple emulsion: a diffusion study.

In order to develop w/o/w emulsions characterized by two separate aqueous phases of different pH, a preliminary study was carried out to obtain a better insight into the possible diffusion processes taking place between an inner acidic aqueous phase and an external phase of higher pH (pH approximately 6). In fact, such systems could be of great interest for pharmaceutical use. For this purpose, a model emulsion was formulated. The study of pH and conductivity showed that acidic species transport take place between the two aqueous compartments. The three main release mechanisms that might be responsible for this passage across the oil phase were investigated: breakdown of oil globules, facilitated transport by surfactant micelles across the oil phase or by Fickian diffusion. It appears that this last mechanism was involved. In order to control this diffusion process, an alkaline species, octadecylamine was introduced in the oil phase. This compound could form an ion pair with the lactate ion at the interface of the external aqueous phase and the oil phase, thus, limiting the acidification of the external aqueous phase.

Algorithms↗

PubMed2001

Formulation of shear rate sensitive multiple emulsions.

This work mainly concentrates on the formulation of W/O/W multiple emulsions capable of breaking and releasing their inner aqueous phase under shear rates compatible with agroalimentary, pharmaceutical and cosmetic applications. Three kinds of multiple emulsions were studied: one with a high concentration of primary emulsion, not viscosified in the external aqueous phase; multiple emulsions gelified with a synthetic polymer (Carbopol 974P((R))); and other multiple emulsions thickened with chemically modified cellulose (hydroxypropylcellulose). The results of this study show the influence of the composition of the external aqueous phase of the emulsions on their fragmentation and release as a function of the shear rate. Despite these differences of behavior with respect to the shear rate, each emulsion fits to Taylor's theoretical framework, indicating that the bursting mechanisms of the globules under shear are the same whatever the composition of the multiple emulsions.

Chemistry, Pharmaceutical↗

PubMed2001

Study of the breakup under shear of a new thermally reversible water-in-oil-in-water (W/O/W) multiple emulsion.

PURPOSE: Thickening of the external aqueous phase of W/O/W multiple emulsions is essential to increase the release under shear. However, it leads to globules bursting during fabrication. To reduce this problem, we have tested a novel thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple emulsion (EMPME) would gel only at skin temperature, which may increase the active ingredient delivery when topically applied. METHODS: Samples were sheared at different shear rates and temperatures (20, 30, and 35 degrees C) with a controlled rheometer. A granulometric analysis was then performed with a laser diffraction granulometer, to assess the break up as a function of the shear rate at the three temperatures. Conductometric measurements (CDM 230 conductometer) provided the corresponding release curves. RESULTS: As we expected, EMPME exhibited a thermally reversible behavior. Compared to a reference emulsion thickened by carbopol, this new thermo-sensitive multiple emulsion displayed higher break up and fraction released at 35 degrees C. CONCLUSION: The first thermally reversible multiple emulsion has been developed in the present work. This one presents interesting advantages: (1) an easy fabrication process with a higher entrapment yield and (2) a higher fraction released at 35 degrees C compared with the reference emulsion.

Acrylic Resins↗

PubMed2001

Poloxamer 407 as a thermogelling and adhesive polymer for rectal administration of short-chain fatty acids.

OBJECTIVES: The purpose of the study was to gel a rectal solution of short-chain fatty acids to decrease the loss of active materials in the colonic lumen and thereby optimize their absorption. METHODS: Five thermogels were prepared with poloxamer 407 at concentrations ranging from 17% to 20%. Their viscosities were measured at room temperature and 37 degrees C, and their gelling temperatures were determined. The adhesive properties of each gel were assessed in vitro at 37 degrees C. Short-chain fatty acid release was studied using Guyot cells. RESULTS: From the threshold concentration of 17.5%, the solutions, Newtonian at room temperature (50-80 mPa x s), gelled at 37 degrees C. The higher the concentration, the higher the viscosity (1750 to 49,000 mPa x s), the lower the gelling temperature (27.6 degrees C to 23.4 degrees C), and the stronger the work of adhesion (2.2 to 4.5 mJ). Short-chain fatty acid release from the 18% polymer gel was decreased by 60% compared to the rectal solution. CONCLUSION: The 18% poloxamer 407 concentration provided a solution that was liquid at room temperature, that gelled at 37 degrees C, possessed adhesive properties, and controlled short-chain fatty acid release.

Absorption↗

PubMed2000

Stability study of W/O/W viscosified multiple emulsions.

Stable multiple emulsions with a small proportion of primary emulsion containing different viscosifying agents in the outer aqueous phase were formulated. The multiple systems were assessed by evaluating several parameters, such as the macroscopic aspect, droplet size, release rate, and accelerated stability under elevated temperatures. The effect of different viscosifying agents at different concentrations on the stability and the multiplicity of the multiple emulsions was examined. The viscosity increased by increasing the concentration of the viscosifying agents. It also appeared that the viscosifying agents increased the temperature stability of the multiple emulsions. As a result, the formulation viscosified with Klucel was more stable, while the one prepared with carbomer viscosified the outer phase at much lower concentrations with much better skin feel.

Chemistry, Pharmaceutical↗

PubMed1999

Formulation of a charcoal suspension for intratumoral injection. Study of galenical excipients.

To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery, thus allowing a better localization of the remaining tumor by the surgeon, we developed a formulation containing 10% charcoal suspended in water for parenteral preparations. The present study concerns a new step in the development of the charcoal suspension. We sought to determine whether the addition of various excipients could improve the formulation properties and affect the labeling of tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate 80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated silica. Except for glucose and mannitol, which were added at a 5% concentration, the other excipients were added at a 0.1% concentration, they were dissolved in water for parenteral injection and sterilized at 120 degrees C for 20 min. We then measured diffusion in vivo in mammary tumor. In vivo, when injected intratumorally in mice, a greater diffusion of charcoal particles was noted within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40, and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol). Pluronic F68 slightly improved the stability of the suspension and did not lead to marked diffusion at the injection site, but it showed slight toxicity and cannot be used in the formulation. We concluded that the best formulation was an aqueous 10% micronized peat charcoal suspension.

Adenocarcinoma↗

PubMed1998

Hydrogels of poly(ethylene glycol): mechanical characterization and release of a model drug.

Thermosensitive polymer networks were synthesized from poly(ethylene glycol), hexamethylene diisocyanate and 1,2,6-hexanetriol in stoichiometric proportions. By varying the amount of 1,2,6-hexanetriol and the molar mass of the poly(ethylene glycol), a wide range of networks with different crosslinking densities was prepared. The networks obtained were characterized by the temperature dependence of their degree of equilibrium swelling in water and by their Young's moduli. For each network, the molecular weight between crosslinks was estimated. The structure of the hydrogels was analysed with respect to scaling laws, and it was found that the results obtained with PEG 1500 and PEG 6000 hydrogels are in agreement with theoretical predictions, whereas those obtained with PEG 400 hydrogels are in disagreement. The release properties of PEG hydrogels were studied by the determination of the diffusion coefficient for acebutolol chlorhydrate and by an analysis of the effect of temperature on these coefficients. Finally, these release properties were correlated with the swelling and structural properties of the hydrogels.

Acebutolol↗

PubMed1998

Kinetics of swelling-breakdown of a W/O/W multiple emulsion: possible mechanisms for the lipophilic surfactant effect.

The properties and behavior of a W/O/W multiple emulsion formulation were analyzed during a swelling-breakdown process. Various experimental analyses, such as granulometry, rheology and conductimetry were performed, as well as a micropipette aspiration method. The predominant role of the lipophilic surfactant during the swelling phase confirmed. Two different mechanism can be proposed. Both imply the migration of the lipophilic surfactant from one interface to another and probably take place successively. The lipophilic surfactant could diffuse from the first to the second interface, thus rigidifying the membrane, or from the oily phase to the first interface, resulting in delayed coalescence of the aqueous droplets during swelling.

Emulsions↗

PubMed1997

Formulation of a charcoal suspension for intratumor injection. Part 1: Study of the nature, granulometry, and concentration.

PURPOSE: We developed a charcoal suspension formulation to be injected intratumorally so that human breast cancers can be tatooed prior to chemotherapy. This deposit is intended to guide the surgeon at the time of the biopsy and resection, especially when the tumor nodule is not visible. The stain should remain in the tumor as long as the patient is on chemotherapy and should be harmless. METHODS: We studied on the effect on the nature of the charcoal, its granulometric profile, and its concentration. We then measured diffusion in vitro, in gel, and in vivo in experimental tumors. RESULTS: The formulation selected was prepared with a peal charcoal suspension in water for parenteral injections, with 50% of the particles measuring on average between 2 and 5 microns. The finest particles (< 2 microns) seem to produce the greatest in vitro diffusion and are more readily phagocyted by macrophages and thus eliminated from the tumor by those cells. CONCLUSIONS: This charcoal suspension has satisfactory formulation characteristics and diffuses the least, be it in vitro or in vivo, mainly due to the granulometric distribution of the suspension.

Animals↗

PubMed1996

[Dynamic viscosity and corneal endothelial protection with Healonid, Healon GV, Provisc and Viscoat during phacoemulsification].

PURPOSE: To demonstrate the utility of a viscoelastic substance which maintains high viscosity during phacoemulsification, we conducted a double study. METHODS: We compared in vitro the corneal endothelial protection offered by Healon, Healon GV, Provisc and Viscoat after < > phacoemulsification. Eight samples of ten to fifteen freshly enucleated pig eyes were operated; the first four groups were the controls, whereas the other four tested the different viscous solutions. In parallel, we determined the rheologic properties of the four viscoelastic substances in a physicS laboratory. To measure the percentage of corneal endothelial cell damage, we used the Janus Green spectrometric technique. RESULTS: Corneal endothelial cell damage averaged 31.67% in eyes in which no viscoelastic substance was used. Damage was 14.29% in specimens that received Healon, 12.85% with Healon GV, 2.48% in the Viscoat group and 15.43 in those that received Provisc. There is a significant difference (p <0.001) between the Viscoat group and all other samples. The values of the viscosity at different shear rates and the graph of viscosities as a function of shear rate of the four viscous solutions are given. CONCLUSION: Viscoat has a very high dynamic viscosity at high shear rate. This property and a poor cohesion provide a better corneal endothelial protection during in vitro phacoemulsification.

Animals↗

PubMedDate not supplied

Insulin in w/o/w multiple emulsions: preparation characterization and determination of stability towards proteases in vitro.

In this work two w/o/w multiple emulsions composed of soybean oil or medium-chain triglycerides and containing insulin were studied. These emulsions were prepared by means of two-step emulsification procedure. The w/o/w emulsions obtained were stable for at least 6 months of storage at 4-6 degrees C. The yield of encapsulation of insulin was > 95%. The main release mechanism is a swelling-breakdown phenomenon. In vitro, the two w/o/w multiple emulsions were able to protect insulin against enzymatic degradation. These results indicate that multiple emulsions have potential as a carrier of insulin for oral administration.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Insulin in w/o/w multiple emulsions: biological activity after oral administration in normal and diabetic rats.

In this work the biological effects of two w/o/w multiple emulsions composed of the soybean oil (EHS) or medium-chain triglycerides (ETCM), containing insulin, were studied. The release mechanism of insulin from multiple emulsions proposed in our previous in-vitro investigations was confirmed by subcutaneous administration. This mechanism is the swelling-breakdown phenomenon which occurs when the emulsions are diluted under hypo-osmotic condition. The biological effect after oral administration, evaluated in two experimental protocols, single administration in normal and diabetic rats and short-term treatment in diabetic rats, shows that in diabetic rats small amounts of biologically active insulin were absorbed from these emulsions. In these experiments no significant difference between EHS and ETCM was found.

Administration, Oral↗