Biomedical subjects

J P Remon

Publications and source records attributed to J P Remon.

At least 19 recordsLinked to original sources

PubMed2006

Influence of particle size on the quantitative determination of salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy.

A second order polynomial calibration model was developed and statistically validated for the direct and non-destructive quantitative analysis - without sample preparation - of the active pharmaceutical ingredient (API) salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy. The calibration curve was modeled by plotting the peak intensity of the vector normalized spectral band between 757 and 784cm(-1) against the known salicylic acid concentrations in standards. At this band, no spectral interferences from the ointment vehiculum (white vaseline) are observed. For the validation of the polynomial model, its fit and its predictive properties were evaluated. The validated model was used for the quantification of 25 ointments, compounded by different retail pharmacists. The same standards and samples were used, both for development and validation of a regression model and for quantitative determination by HPLC - with sample preparation - as described for the related substances of salicylic acid in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the HPLC results (p=0.22), provided that the particle size of salicylic acid in the standards is the same as in the analyzed samples. The non-destructive FT-Raman method is a reliable alternative for the destructive HPLC method, as it is faster and does not require sample pre-treatment procedures.

Calibration↗

PubMed2006

Raman spectroscopy as a process analytical technology tool for the understanding and the quantitative in-line monitoring of the homogenization process of a pharmaceutical suspension.

The aim of this study was to propose a Process Analytical Technology (PAT) strategy for the quantitative in-line monitoring of an aqueous pharmaceutical suspension using Raman spectroscopy. A screening design was used to study the significance of process variables (mixing speed and height of the stirrer in the reactor) and of formulation variables (concentration of the active pharmaceutical ingredient (API) ibuprofen and the viscosity enhancer (xanthan gum)) on the time required to homogenize an aqueous pharmaceutical model suspension as response variable. Ibuprofen concentration (10% and 15% (w/v)) and the height of stirrer (position 1 and 2) were discrete variables, whereas the viscosity enhancer (concentration range: 1-2 g L-1) and the mixing speed (700-1000 rpm) were continuous variables. Next, a multilevel full factorial design was applied to study the effect of the remaining significant variables upon the homogenization process and to establish the optimum conditions for the process. Interactions between these variables were investigated as well. During each design experiment, the conformity index (CI) method was used to monitor homogeneity of the suspension mixing system in real-time using Raman spectroscopy in combination with a fibre optical immersion probe. Finally, a principal component regression (PCR) model was developed and evaluated to perform quantitative real-time and in-line measurements of the API during the mixing process. The experimental design results showed that the suspension homogenization process is an irregular process, for which it is impossible to model the studied variables upon the measured response variable. However, applying the PCR model it is possible to predict in-line and real-time the concentration of the API in a suspension during a mixing process. In this study, it is shown that Raman spectroscopy is a suitable PAT tool for the control of the homogenization process of an aqueous suspension. Raman spectroscopy not only allowed real-time monitoring of the homogeneity of the suspension, but also helped (in combination with experimental design) to understand the process. Further, the technique allowed real-time and in-line quantification of the API during the mixing process.

Chemistry, Pharmaceutical↗

PubMed2006

Xanthan gum to tailor drug release of sustained-release ethylcellulose mini-matrices prepared via hot-melt extrusion: in vitro and in vivo evaluation.

Mini-matrices (multiple-unit dosage form) with release-sustaining properties were developed by means of hot-melt extrusion using ibuprofen as the model drug and ethylcellulose as sustained-release agent. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase the drug release since ibuprofen release from the ibuprofen/ethylcellulose matrices (60/40, w/w) was too slow (20% in 24 h). Changing the xanthan gum concentration as well as its particle size modified the in vitro drug release. Increasing xanthan gum concentrations yielded a faster drug release due to a higher liquid uptake, swelling and erosion rate. Regarding the effect of the xanthan gum particle size, no difference was observed for formulations containing 10% and 20% xanthan gum. However, using 30% xanthan gum, drug release was influenced by the particle size of the hydrophilic polymer due to the susceptibility of the coarser xanthan gum particles to erosion. Drug release from the mini-matrices was mainly diffusion controlled, but swelling played an important role to obtain complete drug release within 24 h. Drug release was influenced by the ionic strength of the medium as the conformation of xanthan gum molecules is determined by the salt concentration. An oral dose of 300 mg ibuprofen was administered to dogs (n=6) in a cross-over study design either as an immediate-release preparation (Junifen), as a sustained-release formulation (Ibu-Slow 600 mg (1/2 tablet)) or as the experimental mini-matrices (varying in xanthan gum concentration). Administration of the experimental formulations sustained the ibuprofen release. Although a significant difference in dissolution rate of the 20% and 30% xanthan gum mini-matrices was detected in vitro, the difference in relative bioavailability was limited (70.6% and 73.8%, respectively).

Animals↗

PubMed2006

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Administration, Intranasal↗

PubMed2006

Medication use and disease control of asthmatic patients in Flanders: a cross-sectional community pharmacy study.

The aim of this study was to describe medication use and disease management of asthmatic patients and to evaluate the usefulness of the Asthma Control Test (ACT) in community pharmacies. In 54 Flemish community pharmacies 166 asthmatic patients were included in the study. At inclusion, the study persons completed a survey to assess subject characteristics, symptoms and asthma attacks, and peak expiratory flow (PEF) was measured. Furthermore, the actual level of asthma control was assessed by ACT, a clinically validated measure of asthma control. Prescribed medicine data of the patients were 1 year retrospectively analysed from the prescriptions. Mean age of the sample was 36.8 year, 23% were smokers. As maintenance treatment, 63% of the patients used a combination product containing an inhaled corticosteroid and a long-acting beta2-agonist in a single inhaler. According to ACT, 49.1% of the patients were insufficiently controlled. Only 4.9% of the patients had a maximal ACT score of 25, indicating complete asthma control; 46.0% of the study population obtained an ACT score between 20 and 24, meaning that their asthma is well controlled. In contrast, 30.7% of the patients had a score between 15 and 19, indicating uncontrolled asthma. In all, 18.4% obtained ACT scores of less than 15, meaning that their asthma was seriously out of control and necessitating referral to their general practitioner or lung specialist. Importantly, the correlation between the self-perceived level of asthma control and the objective assessment of the asthma control level was poor: 82.3% of the patients believed their asthma to be totally or well controlled, while this was the fact for only 50.9% of the patients. In conclusion, the ACT appears to be a useful tool to determine rapidly and accurately the level of asthma control in patients presenting at community pharmacies.

Adult↗

PubMed2006

Deposition of differently sized airborne microspheres in the respiratory tract of chickens.

As a part of the development of an efficient dry powder aerosol vaccine for poultry, the objective of this study was to accurately determine the deposition pattern of nebulized microspheres in the airways of unanaesthetized chickens of different ages (1 day, 2 weeks and 4 weeks old). In the first part of the study, the aerosol administration method was characterized: the influence of different nebulizers and nebulizing protocols on the relative humidity in the exposure chamber, the particle size distributions, the microsphere output and single microsphere percentage were determined. In the second part, birds were exposed to nebulized fluorescently labelled polystyrene microspheres (1 to 20 microm). Respiratory and gastro-intestinal tract tissue samples were collected and the number of fluorescent microspheres per sample was determined. In 2-week-old and 4-week-old chickens, microspheres of 5 and 10 microm, respectively, were too large for deposition in the lungs and air sacs as less than 5% of these microspheres penetrated into the lower airways. The larger size of microspheres reaching the lower airways of 4-week-old birds was explained by increasing airway dimensions with age. For 1-day-old chickens, deposition in the lungs decreased from 17 to 3% with increasing particle size (1 to 20 microm), but increased in the air sacs from 6 to 20%. Consequently, the total deposition percentage in the lower airways was independent of microsphere size and even 20 microm particles were able to penetrate into the lower airways, which was attributed to mouth breathing of the 1-day-old chickens.

Aerosols↗

PubMed2005

Human bioavailability of propranolol from a matrix-in-cylinder system with a HPMC-Gelucire core.

The bioavailability of propranolol from a matrix-in-cylinder system for sustained drug delivery, consisting of a hot-melt extruded ethylcellulose pipe surrounding a drug-containing HPMC-Gelucire 44/14 core, was determined. An oral dose of 80 mg propranolol hydrochloride was administered to healthy volunteers (n = 10) in a randomized cross-over study design either as a commercial pellet formulation (Inderal retard mitis) or as a matrix-in-cylinder system. The influence of concomitant food intake on drug release from the matrix-in-cylinder system was also studied. During the first 10 h after administration, the matrix-in-cylinder system resulted in similar plasma levels as the reference formulation Inderal. The concomitant intake of a high-fat, high-calorie breakfast did not cause dose-dumping. Between 10 h and 24 h after administration of the matrix-in-cylinder system, a remarkable increase of the propranolol plasma levels was noticed (compared to Inderal). This effect was even more pronounced under fed conditions. The matrix-in-cylinder system had a relative bioavailability of 156% (fasted conditions) and 222% (fed conditions) compared to the marketed reference product. In order to elucidate the origin of this increased bioavailability, Caco-2 experiments and dog lymph studies were performed. However, none of these experiments was able to provide a conclusive answer.

Adolescent↗

PubMed2005

Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components.

The purpose of this study was to evaluate different bioadhesive ocular formulations based on drum dried waxy maize starch (DDWM), Amioca starch and Carbopol 974P. The concentrations of Carbopol 974P in the mixtures varied between 5 and 25% (w/w). The rheological properties of the non-sterilized and gamma-irradiated physical blends of Carbopol 974P with either DDWM or Amioca were compared to those of the corresponding co-spray dried Amioca starch/Carbopol powders. Higher viscosity or consistency values were measured for sterilized co-spray dried powder mixtures containing an amount of Carbopol 974P equal or above 15% (w/w) compared to the physical blends. Sustained release minitablets (2 mm, 6 mg), consisting of sodium fluorescein as model drug and the bioadhesive powders, were manufactured at a compression force of 1.25 kN. Afterwards, the tablets were sterilized with gamma-irradiation. The amount of Carbopol in the co-spray dried powder mixtures on the one hand and gamma-irradiation on the other hand had no significant influence on the crushing strength and friability of the minitablets evaluated. However, these two factors affected the in vitro release properties of the minitablets. The slowest release was obtained with tablets containing 25% Carbopol 974P, which unfortunately possess mucosal irritating properties. By using co-spray dried Amioca with 15% (w/w) Carbopol 974P, a slower release can be achieved compared to the physical mixtures of DDWM or Amioca starch with Carbopol 974P. Moreover, this ocular formulation is very promising and is preferred, as it did not cause any mucosal irritation and released the model drug for at least 12 h, after application in the fornix.

Acrylic Resins↗

PubMed2005

Spray-dried Amioca starch/Carbopol 974P mixtures as buccal bioadhesive carriers.

In the present study, spray-dried Amioca starch/Carbopol 974P mixtures were evaluated as potential buccal bioadhesive tablets. Carbopol (C 974P) concentrations from 5 to 75% were tested. All spray-dried mixtures showed a comparable or better bioadhesive capacity compared to a reference formulation (DDWM/C 974P 95/5). The bioadhesive capacities of Amioca/Carbopol 974P mixtures were improved by spray-drying. All spray-dried mixtures showed significantly higher work of adhesion values compared to their equivalent physical mixtures. The influence of Carbopol concentration on the in vivo adhesion time of placebo tablets and in vitro miconazole nitrate release was tested. The ratio Amioca/C 974P 70/30 showed the longest in vivo adhesion time (24.5+/-8.5 h). Lower and higher C 974P concentrations had a shorter in vivo adhesion time. The mixtures containing between 15 and 30% C 974P could all sustain the in vitro miconazole nitrate release over 20 h. Again, lower and higher C 974P concentrations showed a faster in vitro miconazole release. The drug loading capacity of a spray-dried mixture containing 20% C 974P was investigated in vivo in dogs using testosterone as model drug. The spray-dried mixture could be loaded with 60% drug without loosing its in vivo bioadhesive and pharmacokinetic properties.

Acrylates↗

PubMed2005

Starch/Carbopol spray-dried mixtures as excipients for oral sustained drug delivery.

The present study evaluated if mixtures prepared by spray-drying an aqueous dispersion of Amioca starch and Carbopol 974P could be used as matrix for oral sustained drug delivery. The influence of the Amioca/Carbopol 974P ratio (0/100, 25/75, 50/50, 60/40, 85/15, 90/10, 95/5 and 100/0) and the pH and ionic strength (mu) of the dissolution medium on the drug release was investigated. The matrices composed of the spray-dried mixtures with 10% or 15% Carbopol 974P sustained the drug release over the longest time period. At this Carbopol concentration, shear viscosity measurements indicated the formation of an optimal network between the polymer chains of Amioca starch and Carbopol 974P, forming a rigid gel layer offering resistance to erosion during the dissolution experiments.

Acrylic Resins↗

PubMed2005

Development of an enteric-coated pellet formulation of F4 fimbriae for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections.

A multi-particulate formulation of F4 fimbriae was developed for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections. A feasibility test showed that incorporation of F4 fimbriae in a disintegrating pellet formulation consisting of 87.5% Pharmatose 200 M, 2.5% Avicel CL 611 and 10% Explotab by extrusion/spheronisation and subsequent fluid bed drying resulted in the maintenance of 69+/-12% of the biological activity. But subsequent coating resulted in pellets with poor enteric properties, although good in vivo immunising results were obtained after administration to piglets. From the economical point of view, a pellet formulation was optimised to decrease vaccine dose and dosing frequency. After disintegration testing, pellets consisting of lactose (alpha-lactose monohydrate 90 mesh/beta-lactose 75/25 (w/w)) and microcrystalline cellulose in a ratio of 80/20 (w/w) showed a sponge-like structure from which F4 fimbriae could be released. Coating of these pellets resulted in good enteric properties. To improve disintegrating properties of the pellets, the lactose concentration was increased or sodium carboxymethyl starch was added. But this resulted in poor enteric properties after coating. Dissolution test showed that F4 fimbriae were released from the optimised enteric-coated pellets but interaction between F4 fimbriae and the coating polymer was seen. This incompatibility leads to unpredictable in vitro quantification of F4 biological activity.

Administration, Oral↗

PubMed2005

Refinement of the Slug Mucosal Irritation test as an alternative screening test for eye irritation.

The objective of this study was to limit the test procedure time of the Slug Mucosal Irritation test to one day and to determine whether it is a relevant and reliable method to predict the eye irritation potential of chemicals. The irritation potential of several eye reference chemicals can be estimated by the amount of mucus produced when tested at a 1% concentration (60 min). Since some in vivo irritating chemicals did not influence this endpoint the effect of increasing concentrations on membrane damage was investigated. This study revealed that when tested at a 3.5% concentration (60 min) the underestimated chemicals induced an increased protein and/or enzyme release. A two-step classification prediction model was developed that classified the chemicals first by the amount of mucus produced (1%, 60 min). Chemicals that did not affect this endpoint were classified based on the membrane damage induced by a second treatment (3.5%, 60 min). The results were compared with the corresponding EU classification (NI, R36 and R41) and 71% of the chemicals were correctly classified with a specificity and sensitivity of 75% and 94%, respectively. Repeated testing of the chemicals revealed a good intra-laboratory reproducibility. The test seems to be a promising method for screening the eye irritating potential of chemicals.

Animal Testing Alternatives↗

PubMed2005

Tablets prepared by single-step granulation/tabletting: interparticulate binding mechanism and stability.

The binding mechanism of tablets prepared by single-step granulation/tabletting (SSGT), a novel technique for the production of tablets, was evaluated. SSGT yielded hard tablets having a short disintegration time due to their porous, spongelike internal structure. Calculation of the interaction factor and electrical conductance tests confirmed the presence of solid bridges that provided a higher tensile strength to these compacts in comparison to tablets prepared by conventional tabletting techniques. At high relative humidity, moisture sorption and glass-to-rubber transition of the binder (polyvinylpyrrolidone), or condensation of moisture on the internal pore surface, reduced the tensile strength of the SSGT-manufactured tablets. Contrary to tablets prepared by granulation and compression, the SSGT tablets did not harden during storage under conditions of varying relative humidity (alternating the relative humidity every 24 hr between 33% and 75%).

Drug Stability↗

PubMed2004

In vitro and in vivo evaluation of a matrix-in-cylinder system for sustained drug delivery.

A matrix-in-cylinder system for sustained drug delivery, consisting of a hot-melt extruded ethylcellulose (EC) pipe surrounding a drug containing HPMC-Gelucire 44/14 core, was evaluated in vitro and in vivo. In an aqueous medium, the HPMC-Gelucire core forms a gel plug, which releases the drug-through the open ends of the EC pipe--by means of erosion. The influence of hydrodynamic and mechanical stress and the effect of different 'physiologically relevant' dissolution media on the in vitro drug release were investigated. From these in vitro dissolution tests, it was concluded that the EC pipe has a protective effect on the drug containing HPMC-Gelucire core. It largely protects the core against hydrodynamics and mechanical stress. Furthermore, drug release from the matrix-in-cylinder system was only slightly affected by the composition of the dissolution medium. A randomised crossover in vivo study in dogs revealed that the matrix-in-cylinder system containing propranolol hydrochloride has an ideal sustained release profile with constant plasma levels maintained over 24 h. Moreover, administration of the matrix-in-cylinder system resulted in a 4-fold increase in propranolol bioavailability when compared with a commercial sustained release formulation (Inderal).

Administration, Oral↗

PubMed2004

Twin screw granulation as a simple and efficient tool for continuous wet granulation.

The modification of a twin screw extruder for continuous wet granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw granulation was evaluated by studying the influence of processing parameters and formulation variables on the process performance and on the properties of alpha-lactose monohydrate granules and tablets. The process reproducibility during long term production was evaluated. Screw speed (200-450 rpm) and total input rate (5.5-9.5 kg/h) had no significant influence on the granule properties, while the water concentration during granulation influenced the process as well as the granule properties. At a water concentration (calculated on wet granule basis) of 5.5-8.5%, continuous twin screw granulation of alpha-lactose monohydrate 200 M was feasible and the granules obtained had good properties. PVP addition mainly affected tablet properties. Tablets made from granules containing 2.5% PVP had a tensile strength above 0.94 MPa, a friability below 1% and a disintegration time ranging between 495 and 576 s. Tablets containing hydrochlorothiazide complied with the dissolution requirements as 60% was released after 5 and 15 min from tablets without PVP and with 2.5% PVP, respectively. No problems were observed during continuous twin screw granulation over a period of 8h and the granule and tablet properties were reproducible throughout the process. These results indicated that twin screw granulation is an efficient tool for continuous wet granulation.

Excipients↗

PubMed2004

Hot-melt extruded ethylcellulose cylinders containing a HPMC-Gelucire core for sustained drug delivery.

The objective of the study was to develop a sustained release system consisting of a hot-melt extruded ethylcellulose pipe surrounding a drug-containing hydroxypropyl methylcellulose (HPMC)-Gelucire 44/14 core, yielding a monolithic matrix system applicable in the domain of sustained drug release. The influence of HPMC substitution type and viscosity grade was investigated through dissolution testing and erosion studies. All sustained release systems showed a nearly constant drug release profile with only 40% of the drug released after 24 h. To achieve complete drug release after 24 h, the core formulation and the dimensions of the hollow pipe were modified. Changing the composition of the core did not result in the intended zero-order drug release. Shortening the length of the ethylcellulose cylinder accelerated drug release, while modifying the diameter did not affect the drug release rate. The drug dissolution profile and the release mechanism were independent of drug solubility. Increasing the drug loading caused a small increase of the drug release rate, but did not alter the release mechanism.

Cellulose↗

PubMed2004

Gastrointestinal transit time of nondisintegrating radio-opaque pellets in suckling and recently weaned piglets.

The objective was to determine the gastrointestinal (GI) transit times of pellets in piglets at different time points around weaning, as transit times are essential criteria to develop oral drug delivery systems. Nondisintegrating radio-opaque pellets were given orally in order to define the transit times by radiography. The radiographs were analysed with a software programme to calculate the number of pellets present in the different parts of the GI tract. In suckling piglets, the gastric emptying was faster (75% in 1.5 to 3.5 h), and the colonic accumulation (to 73%) was greater than in weaned piglets (3 days, 2 and 3 weeks postweaning, 65% gastric emptying in 18 h, 75% in 17 h, and 75% in 7 h, respectively; maximal colonic accumulations of 48%). Immediately after weaning, the transit was markedly prolonged but shortened with increased postweaning time (3 days, 2 and 3 weeks postweaning, 85% excretion in 175.5, 77, and 50.5 h, respectively). Three weeks postweaning, the transit was no longer affected by weaning as transit times were similar to values reported in growing and adult pigs, and retention appeared to be restricted to the stomach and the colon. These data are of crucial importance in the design of enteric-coated formulations for oral administration of vaccines and therapeutics to young piglets and for human research using the pig model.

Animals↗

PubMed2004

Quantitative determination of p-aminosalicylic acid and its degradation product m-aminophenol in pellets by ion-pair high-performance liquid chromatography applying the monolithic Chromolith Speedrod RP-18e column.

An ion-pair high performance liquid chromatographic method was developed for the simultaneous determination of p-aminosalicylic acid (PAS) and its degradation product m-aminophenol (MAP) in a newly developed multiparticular drug delivery system. Owing to the concentration differences of PAS and MAP, acetanilide and sulfanilic acid were used as internal standards, respectively. The separation was performed on a Chromolith SpeedROD RP-18e column, a new packing material consisting of monolithic rods of highly porous silica. The mobile phase composition was of 20 mm phosphate buffer, 20 mm tetrabutylammonium hydrogen sulphate and 16% (v/v) methanol adjusted to pH 6.8, at a flow-rate of 1.0 mL/min, resulting in a run-time of about 6 min. Detection was by UV at 233 nm. The method was validated and proved to be useful for stability testing of the new dosage form. Separation efficiency was compared between the new packing material Chromolith SpeedROD RP-18e and the conventional reversed-phase cartridge LiChroCART 125-4 (5 microm). A robustness test was carried out on both columns and different separation parameters (retention, resolution, run time, temperature) were determined.

Aminophenols↗