Biomedical subjects

J P Remon

Publications and source records attributed to J P Remon.

At least 37 records · Page 2Linked to original sources

PubMed2004

Single-step granulation/tabletting of different grades of lactose: a comparison with high shear granulation and compression.

The influence of the particle size, particle morphology and crystallinity of lactose on the extrusion properties and on the quality of tablets were investigated using single-step granulation/tabletting as a tabletting technique. Results showed that particle size and type of lactose (alpha-lactose monohydrate, anhydrous beta-lactose and spray dried lactose) affected the powder feeding, the process performance as well as the process capacity. Different grades of lactose yielded tablets with similar tensile strength, but significantly different disintegration time. Single-step granulation/tabletting always yielded tablets with a significantly higher tensile strength and similar or significantly lower disintegration time compared to high shear granulation and compression. The tensile strength of alpha-lactose monohydrate tablets (without and with PVP) did not change during one year of storage at 60% RH-25 degrees C and at 75% RH-40 degrees C, whereas a significant increase in disintegration time was observed. It can be concluded that although the lactose grade affected the performance and the optimal parameters of single-step granulation/tabletting, all lactose grades can be efficiently processed using this technique.

Compressive Strength↗

PubMed2004

In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy.

FT-Raman spectroscopy (in combination with a fibre optic probe) was evaluated as an in-line tool to monitor a blending process of diltiazem hydrochloride pellets and paraffinic wax beads. The mean square of differences (MSD) between two consecutive spectra was used to identify the time required to obtain a homogeneous mixture. A traditional end-sampling thief probe was used to collect samples, followed by HPLC analysis to verify the Raman data. Large variations were seen in the FT-Raman spectra logged during the initial minutes of the blending process using a binary mixture (ratio: 50/50, w/w) of diltiazem pellets and paraffinic wax beads (particle size: 800-1200 microm). The MSD-profiles showed that a homogeneous mixture was obtained after about 15 min blending. HPLC analysis confirmed these observations. The Raman data showed that the mixing kinetics depended on the particle size of the material and on the mixing speed. The results of this study proved that FT-Raman spectroscopy can be successfully implemented as an in-line monitoring tool for blending processes.

Fourier Analysis↗

PubMed2004

Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation.

The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis.

Adhesives↗

PubMed2004

Development and validation of a direct, non-destructive quantitative method for medroxyprogesterone acetate in a pharmaceutical suspension using FT-Raman spectroscopy.

A simple linear regression method was developed and statistically validated for the direct and non-destructive quantitative analysis--without sample preparation--of the active pharmaceutical ingredient (API) medroxyprogesterone acetate (MPA) in an aqueous pharmaceutical suspension (150 mg in 1.0 ml) using FT-Raman spectroscopy. The linear regression was modelled by plotting the highest peak intensity of the vector normalized spectral band between 1630 and 1590 cm-1 against different MPA standard suspension concentrations. At this band, no spectral interferences from additives in the suspension are observed. The validated model was used for the quantification of a commercial suspension (150 mg in 1.0 ml) of the commercialized preparations. The same standards and samples were used, respectively, for the development and validation of a simple linear regression model and for the quantitative determination by means of HPLC-with sample preparation-as described for the related substances of MPA in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the claimed label concentration (150.01+/-0.96 mg/ml (n=6)). Applying the HPLC method, however, a systematic error was observed (157.77+/-0.94 mg/ml (n=6)). The direct FT-Raman method hence appears the most reliable for the quantification of the MPA component in suspension, compared to the HPLC method that requires sample preparation. The latter method provides a systematic error because the exact volume or density of a suspension sample is unknown. A precise isolation of fixed volumes from a suspension is rather unfeasible because of the continuous sagging of the suspended particles and their sticking to the used materials in the isolation process.

Chromatography, High Pressure Liquid↗

PubMed2004

The quality of essential antimicrobial and antimalarial drugs marketed in Rwanda and Tanzania: influence of tropical storage conditions on in vitro dissolution.

OBJECTIVE: The quality of 33 formulations of essential antimicrobial and antimalarial drugs (amoxicillin capsules, metronidazole tablets, sulfamethoxazole/trimethoprim tablets, quinine tablets and sulphadoxine/pyrimethamine tablets) marketed in Rwanda and Tanzania was assessed and the influence of tropical storage conditions on potency and in vitro dissolution investigated. METHODS: Drug content and in vitro dissolution were determined immediately after purchase and during 6-month storage under simulated tropical conditions (75% relative humidity, 40 degrees C) using the methods described in the USP 24 monographs on the drugs concerned. RESULTS AND DISCUSSION: At the time of purchase, the drug content of all the formulations was within the limits recommended by the USP 24, but after 6-month storage, the drug content of one sulfamethoxazole/trimethoprim and one quinine formulation were found to be substandard. Immediately after purchase, four formulations (three sulfamethoxazole/trimethoprim and one sulphadoxine/pyrimethamine combination) failed the USP 24 dissolution test. Except for three metronidazole and one quinine formulations, dissolution tests performed after 6 months of storage under simulated tropical conditions showed that drug release remained within the USP 24 recommended values. CONCLUSION: In both countries, essential drug formulations met pharmacopoeial potency requirements, but some had a poor in vitro drug release profiles. Some of the formulations tested were not stable upon storage under simulated tropical conditions.

Anti-Infective Agents↗

PubMed2003

Enteric-coated pellets of F4 fimbriae for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections.

To prevent enterotoxigenic Escherichia coli (ETEC) induced postweaning diarrhoea, the piglet needs an active mucosal immunity at the moment of weaning. In the present study, the feasibility of oral vaccination of suckling piglets against F4+ETEC infection with F4 fimbriae was studied. Furthermore, oral vaccination with enteric-coated pellets of F4 fimbriae was compared to vaccination with F4 fimbriae in solution. Therefore, piglets were orally administered 1mg F4 fimbriae in pellets or in solution during three successive days at the age of 7 and 21 days, whereas control piglets were not vaccinated. Five days postweaning (33 days of age), all animals were orally challenged with F4+ETEC. Despite the induction of an immune response upon oral administration of both F4 fimbriae in pellets as in solution, the colonisation of the small intestine by F4+ETEC upon oral challenge could not be prevented. However, a marginal but significant reduction in F4+ E. coli faecal excretion was found in the piglets vaccinated with F4 fimbriae in pellets, indicating that the use of an enteric-coat which protects the F4 fimbriae against inactivation by milk factors and degradation by enzymes and bile improves vaccination.

Administration, Oral↗

PubMed2003

Comparison of morphine and hydromorphone analysis on reversed phase columns with different diameters.

A comparison of a reversed phase high-performance liquid chromatographic (HPLC) method performed on columns with different internal diameters is reported for the quantitative routine determination of morphine.HCl and hydromorphone.HCl in solutions used for intramuscular injection. The method is based on the ion-pairing properties of sodium dodecyl sulphate (SDS) with alkaloids on a reversed phase LiChrospher RP-18 packing material and UV-detection at 230 nm. The mobile phase consisted of an acetonitrile: water mixture 35:65 (v/v) containing 0.5% (w/v) SDS and 0.4% (v/v) acetic acid. Precision, linearity and limit of detection were compared on the 2, 3 and 4 mm i.d. x 125 mm columns. A robustness test for the determination of hydromorphone.HCl was also evaluated.

Chromatography, High Pressure Liquid↗

PubMed2003

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.

Administration, Oral↗

PubMed2003

Development and evaluation of sustained release mini-matrices prepared via hot melt extrusion.

Sustained release mini-matrices (multiple unit dosage form) were developed by means of hot-melt extrusion using ibuprofen as the model drug and ethyl cellulose as sustained release agent. Ibuprofen release from the ibuprofen-ethyl cellulose matrices (60:40 w/w) was too slow (20% in 24 h). Other excipientia (hydroxypropyl methylcellulose and xanthan gum) were added to the formulation to increase the drug release. Changing the viscosity and substitution type of HPMC, the amount of HPMC, the drug load and the HPMC:EC ratio modified the in vitro drug release. Burst release was noticed for the formulations containing HPMC and a nearly time independent drug release was seen for the xanthan gum based mini-matrices. Drug release from the mini-matrices was mainly diffusion controlled and swelling played an important role to obtain complete drug release. The formulations were at least 12 months stable during storage at 60% RH and room temperature. At a higher relative humidity and temperature the drug release increased.

Delayed-Action Preparations↗

PubMed2003

Characterization and in vivo evaluation of ocular bioadhesive minitablets compressed at different forces.

The influence of the compression force on the physical properties, the in vitro release and the in vivo behavior of ocular minitablets is evaluated in the present study. The bioerodible minitablets (Ø 2 mm, 6 mg) were produced at different compression forces. The crushing strength, friability, water uptake, hydration and swelling of the minitablets both in vitro as well as in vivo after application in the cul-de-sac were evaluated. The friability remained below 1% only for the minitablets made at 0.500 and 0.750 kN. The crushing strength measured was 3.53+/-0.98, 12.34+/-1.69 and 18.64+/-2.37 N for minitablets made at 0.250, 0.500 and 0.750 kN, respectively. The full hydration time equalled 20 and 30 min for minitablets compressed at 0.250 kN and 0.500-0.750 kN, respectively. Increasing the compression force resulted in a decreased swelling capacity. The in vivo release was evaluated in healthy volunteers using a non-invasive method to measure the apparent sodium fluorescein concentration in the tearfilm-cornea compartment as a function of time. The longest residence time of the fluorescent tracer at the administration site was obtained by the minitablets compressed at 0.750 kN. The in vitro release was evaluated with three different dissolution methods: the reciprocating cylinder method, vials in an oscillatory shaking bath and a static method with vials. The best correlation with the in vivo behavior of the matrix minitablets was obtained with the shaking bath method.

Adhesives↗

PubMed2003

Evaluation of the mucosal irritation potency of co-spray dried Amioca/poly(acrylic acid) and Amioca/Carbopol 974P mixtures.

The purpose of this study was to evaluate the biocompatibility of different Amioca/poly(acrylic acid) and Amioca/Carbopol 974P co-spray dried mixtures with an alternative mucosal irritation test using slugs. The irritation potential of the mixtures was measured by the amount of mucus produced during a repeated 30-min contact period. Additionally, membrane damage was assessed by measuring the protein and enzyme release from the body wall of slugs after treatment. All the Amioca/poly(acrylic acid) co-spray dried mixtures (50:50 and 25:75 ratios) induced slight irritation of the mucosal tissue as was demonstrated by the significantly increased mucus production however no increased protein and enzyme release was detected. Co-spray dried Amioca/Carbopol 974P mixtures containing 40% and more Carbopol 974P demonstrated a significantly higher mucus production and release of cytosolic LDH, indicating membrane damage. The total mucus production of the slugs treated with the co-spray dried mixtures containing up to 20% Carbopol 974P was significantly higher compared to the blank slugs. However, these mixtures induced no membrane damage since no additional effect on the protein release and no enzyme release was detected. By co-spray drying up to 20% Carbopol 974P could be incorporated without showing a distinct sign of irritation. These mixtures can be considered as potentially safe bioadhesive carriers.

Acrylates↗

PubMed2003

Rheological study on mucoadhesivity of some nasal powder formulations.

Various powder mixtures were used to administer insulin via the nasal route: a co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1), maltodextrin DE38/Carbopol 974 P (9/1) and pure drum dried waxy maize starch. Oscillatory rheology is performed to study and compare the viscosity, elasticity and mucoadhesivity of these powder formulations. There was no rheological synergism detectable with the co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1) and maltodextrin DE38/Carbopol 974 P (9/1). Interaction due to entanglements was seen with drum dried waxy maize starch (100%). The differences in nasal bioavailability between the different carriers could be explained by differences in G' (storage modulus, elasticity) and G" (loss modulus, viscosity) values. The formulation giving the highest bioavailability, provided also the highest G' and G" values.

Adhesives↗

PubMed2002

Plaque-inhibiting effect of bioadhesive mucosal tablets containing chlorhexidine in a 4-day plaque regrowth model.

BACKGROUND AND AIM: Compliance in the use of daily oral antiseptics can probably be enhanced by prescribing easily-applied bioadhesive tablets which slowly release chlorhexidine (CHX). This could also be of use in patients with difficulties in rinsing or performing mechanical plaque control. The aim of the present study was to evaluate the capacity of bioadhesive tablets containing either 30 mg or 40 mg of CHX to inhibit de novo plaque formation. METHOD: In this single, examiner-blinded, crossover study, 22 volunteers between 21 and 25 years of age refrained from oral hygiene for 4 days. Bioadhesive mucosal tablets containing 30 mg or 40 mg of CHX were applied in the canine region. Rinses with a 0.2% CHX solution and placebo tablets served as controls. Plaque regrowth was evaluated with the Quigley-Hein Index modification of Turesky and by an automatic image analysis system (AIA) using slides of stained plaque. Rinsing and application of the tablets were done under supervision twice daily. RESULTS: According to the plaque index, plaque regrowth was significantly inhibited by CHX rinses ( P<0.001) and by tablets with 40 mg of CHX ( P<0.02) for all teeth and surfaces. Placebo tablets and 30-mg CHX tablets had no plaque-inhibiting effect. For taste, the subjects preferred the placebo and the 30-mg tablets more than the rinses and 40-mg tablets. In 3/22 of the subjects, superficial mucosal lesions were found at the side of application of the 40-mg tablets. Using the AIA system for evaluation of plaque regrowth, similar results for plaque inhibition were found. CONCLUSION: It can be concluded that bioadhesive mucosal tablets containing 40 mg of CHX can inhibit plaque regrowth as well as 0.2% CHX rinses. However, unpleasant taste and superficial mucosal lesions are local side effects to be considered.

Adhesiveness↗

PubMed2002

Bioavailability of hydrochlorothiazide from isomalt-based moulded tablets.

The bioavailability of hydrochlorothiazide (HCT) from moulded isomalt-based tablets was evaluated after oral administration of 50 mg HCT to healthy volunteers as an oral moulded tablet and as a lozenge, in comparison with a conventional tablet formulation (Dichlotride 50 mg). Moulded tablets had a high relative bioavailability (F(rel)) as the pharmacokinetic parameters (C(max), t(max), t(1/2), AUC(0-->24 h)) determined from HCT plasma concentration versus time profiles were not significantly different (P>0.05; two-way ANOVA) in comparison with the conventional tablet. The relative bioavailability of the moulded tablet administered as a lozenge and as an oral tablet was 106.2+/-30.9% and 89.4+/-25.9%, respectively, in relation to the conventional tablet formulation. Direct moulding of isomalt tablets proved to be a suitable technique to administer a poorly soluble drug either as a conventional tablet or as a lozenge.

Administration, Oral↗

PubMed2002

Drug administration to poultry.

Drugs can be administered to birds either individually or as a flock treatment. For poultry, drinking water and feed medication are preferred, but in the case of serious disease, parenteral administration can be an alternative. For an efficient and safe therapy, data on drug pharmacodynamics and pharmacokinetics are required. Therefore, the gastrointestinal anatomy and physiology of birds, and the elimination of drugs in birds are discussed in this review. In addition, important aspects of drinking water medication, such as water quality, individual water uptake, drinking water system, lighting periods and drug formulations are discussed. Also, some requirements concerning feed medication are mentioned. Finally, parenteral and vaccine administration in the poultry industry are described.

Administration, Oral↗

PubMed2002

Evaluation of an alternative mucosal irritation test using slugs.

The objective of this study was to evaluate an alternative mucosal irritation test using the slug Arion lusitanicus as test organism. The effect of 28 reference substances on the mucosal tissue of the slugs was determined by the amount of mucus produced, the reduction in body weight, and the release of proteins from the body wall. The data of the mucosal irritation test were compared with the available in vivo Draize scores for eye irritation (MMAS). The amount of mucus produced and the reduction in body weight caused by a 60-min contact period were significantly correlated (r = 0.73) with the MMAS score for eye irritation. However, the mucus production was the best endpoint to classify the chemicals into the three categories corresponding the EU classification (NI, R36, and R41). Since irritating alcohols did not induce an increased mucus production and therefore the irritation potential of these molecules was underestimated, two prediction models were developed. For nonalcohols a 60-min contact period with the chemicals was sufficient and the molecules were classified according to the amount of mucus produced. A concordance, specificity, and sensitivity of 65, 100 and 83%, respectively, was obtained. For the alcohols a second 60-min contact period was necessary and the molecules were classified using the protein release as endpoint. Ninety-one percent of the alcohols were correctly classified with a sensitivity and specificity of 100%. We can conclude that the mucosal irritation test using slugs seems to be a reliable and promising method for the evaluation of the irritation potential of drugs instead of diverse tests using different animal models to estimate the irritation on human mucosal tissues.

Animals↗

PubMed2002

In vivo evaluation of matrix pellets containing nanocrystalline ketoprofen.

The aim of this study was to evaluate the in-vivo behaviour of matrix pellets formulated with nanocrystalline ketoprofen after oral administration to dogs. No significant differences in AUC-values were seen between pellet formulations containing nanocrystalline or microcrystalline ketoprofen and a commercial ketoprofen formulation (reference: Rofenid 200 Long Acting). C(max) of the formulations containing nano- or microcrystalline ketoprofen was significantly higher compared to reference, whereas t(max) was significantly lower. The in-vivo burst release observed for the spray dried nanocrystalline ketoprofen matrix pellets was reduced following compression of the pellets in combination with placebo wax/starch pellets. These matrix tablets sustained the ketoprofen plasma concentrations during 5.6 and 5.4 h for formulations containing nano- and microcrystalline ketoprofen, respectively.

Administration, Oral↗

PubMed2002

Continuous twin screw extrusion for the wet granulation of lactose.

The suitability of continuous twin screw extrusion for the wet granulation of alpha-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone (PVP) concentration) on the properties of granules (yield, particle size distribution, friability and compressibility) and tablets (tablet tensile strength, friability and disintegration time) was investigated. Variation of the formulation and process parameters had a major effect on the process feasibility. Optimization of these parameters is required to allow continuous processing and to ensure a high yield. Total input rate, screw speed and water concentration had a minor influence on the granule and the tablet properties. The addition of PVP had no major influence on the granule properties, but significantly affected the tablet characteristics. For granules formulated with and without PVP a yield above 50%, a friability below 30% and a compressibility below 15% was obtained. Tablets without PVP showed a tensile strength below 0.6 MPa, a friability above 1% and a disintegration time below 3 min, whereas tablets with PVP showed a tensile strength above 0.6 MPa, a friability below 1% and a disintegration time ranging from 8 to 15 min. High shear granulation was only possible when PVP was added and it required a higher amount of water. It was concluded that wet granulation of alpha-lactose monohydrate using continuous twin screw extrusion is a robust process and might offer a suitable alternative for high shear granulation in the pharmaceutical industry.

Algorithms↗