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Biomedical subjects

J P Remon

Publications and source records attributed to J P Remon.

At least 73 records · Page 4Linked to original sources
PubMed2000

Evaluation of starch-maltodextrin-Carbopol 974 P mixtures for the nasal delivery of insulin in rabbits.

In this study insulin was administered nasally to rabbits as a dry powder formulation. The powders consisted of drum-dried waxy maize starch (DDWM) or maltodextrins with different DE values and Carbopol 974 P. The powders were prepared by freeze-drying a dispersion of these excipients with insulin. Bioavailabilities obtained with the powder formulations containing DDWM/Carbopol 974 P (5 and 10%) were significantly higher (p<0.05) than those containing maltodextrins-Carbopol 974 P mixtures. The bioavailability of the powder formulation containing DDWM and 10% Carbopol 974 P was significantly higher (14.4%) than the bioavailability of the same mixture containing 5% Carbopol 974 P (9.9%). The bioavailability, t(max) and C(max) values of the formulation with 5% Carbopol 974 P were significantly higher in comparison with the formulation without Carbopol 974 P. 10% Carbopol 974 P was required when maltodextrins were used in order to obtain a significantly higher bioavailability compared with the formulations without Carbopol 974 P. Freeze-drying seemed a prerequisite for a good bioavailability from the powder formulation as well as the ratio of insulin versus bioadhesive powder (1 IU and 2 IU/mg of bioadhesive powder).

Acrylates↗
PubMed2000

Matrix mini-tablets based on starch/microcrystalline wax mixtures.

Matrix mini-tablets based on a combination of microcrystalline waxes and starch derivatives were prepared using ibuprofen as a model drug. The production of mini-tablets was preferred over the production of pellets, as up-scaling of the pelletisation process seemed problematic. Prior to tabletting, melt granulation in a hot stage screw extruder and milling were required. The in vitro drug release was varied using microcrystalline waxes with a different melting range, the slowest drug release being obtained with a formulation containing a microcrystalline wax with a melting range between 68 and 72 degrees C. Generally speaking increasing the wax concentration resulted in a slower drug release. In vitro drug release profiles were also modified using different starches and mixtures of starches. Increasing the ibuprofen concentration to 70% resulted in a faster drug release rate.

Capsules↗
PubMed2000

Application of the restricted-access precolumn packing material alkyl-diol silica in a column-switching system for the determination of ketoprofen enantiomers in horse plasma.

The group of LiChrospher ADS (alkyl-diol silica) sorbents that make part of a unique family of restricted-access materials, have been developed as special packings for precolumns used in the LC-integrated sample processing of biofluids. The advantage of these sorbents lies in the direct injection of untreated biological fluids, that is without sample clean-up, the elimination of the protein matrix with a quantitative recovery together with an on-column enrichment. The present method is based on previous work applying UV detection at 260 nm for ketoprofen determinations. Plasma samples introduced to the ADS precolumn using a 0.1 M phosphate buffer, pH 7.0. After washing with the buffer the ADS column was backflushed with the mobile phase 0.01 M phosphate buffer-6% (v/v) 2-propanol-5 mM octanoic acid at a pH of 5.5, thus transporting the analytes to the chiral-HSA (human serum albumin) (100x4.0 mm) column where the separation of the ketoprofen enantiomers was achieved with a resolution factor of 1.4. The developed column-switching method was fully applicable to plasma injections.

Animals↗
PubMed2000

Influence of drying temperature and granulation liquid viscosity on the inter- and intragranular drug migration in tray-dried granules and compacts.

The influence of the drying temperature and granulation liquid viscosity on the inter- and intragranular migration of a poorly water-soluble compound in a granulation mass and in a compact was quantitatively assessed. The intergranular migration kinetics were investigated by evaluating the drug distribution at different drying-time intervals. The results were analyzed by use of two-factor, three-level, face-centered, central composite designs. Riboflavin was mixed with alpha-lactose monohydrate 90 M and granulated with distilled water, except for the viscosity experiments in which an aqueous polyvinylpyrrolidone (PVP) (Kollidon K90) solution was used. The wet granules were dried in a hot-air oven or compacted prior to drying. The drug concentration at different locations inside the granulated mass and the compacts after drying was determined spectrophotometrically and by use of diffuse light reflectance measurements. The riboflavin distribution in the granulation masses and in the compacts was characterized by drug-enriched outer layers and drug-depleted inner regions, indicating a strong migration phenomenon. It was clear that the drying temperature had no influence on the inter- and intragranular drug distribution. The intergranular migration was avoided using the PVP as a binder in the granulation liquid, whereas a minimal granulation liquid viscosity of 100 mPa.sec was necessary to avoid the intragranular migration. The diffuse light reflectance measurements can be used for the in-process control of granule samples containing low drug concentrations without the destruction of the samples.

Hot Temperature↗
PubMed1999

Influence of the process parameters on the characteristics of starch based hot stage extrudates.

The influence of the process parameters on the characteristics of matrix formulations produced by means of hot stage extrusion was investigated using three experimental designs. The first one was designed to evaluate the importance of the screw speed (150-450 rpm) and the feed rate (2-12 kg/h), while the second and the third were designed to study the importance of the temperature profile (60-120 degrees C). The extrudates were produced with a laboratory twin screw extruder equipped with a 3-mm cylindrical die. The formulations consisted of 53% corn starch, 15% sorbitol, 2% glyceryl monostearate and 30% theophylline monohydrate as the model drug. The extrudates were characterized by Karl-Fischer titration, Hg-porosimetry, four-point bending and dissolution testing. From the first design it was concluded that the screw speed and feed rate hardly affected the water content of the extrudates, but that there was a clear influence on the extrudate radius, porosity, mechanical strength and dissolution behaviour. High screw speed-high feed rate processes in comparison with low screw speed-low feed rate processes caused an increase in extrudate radius and porosity and a decrease in mechanical strength and drug release rate from the matrix. It was clear that the contribution of the feed rate was higher than that of the screw speed. Expansion, promoted under certain extrusion conditions, could explain the obtained results. The second and third design revealed that only the maximum barrel temperature and not the whole temperature profile was responsible for the temperature effects on the extrudate characteristics. It was concluded that the maximum barrel temperature was the most critical parameter of the hot stage extrusion process.

Hot Temperature↗
PubMed1999

Characterization and evaluation of isomalt performance in direct compression.

Isomalt is a sugar substitute with a wide range of potential pharmaceutical applications as a result of its physicochemical properties. Four grades of this material were evaluated for their physical characteristics. Only Palatinit(R) C and F exhibited potential characteristics for direct compression. As expected, the products required lubrification for tabletting. A level of 1% lubricant gave the best performance for Palatinit(R) C, the most compressible grade as shown by compaction profiles generated using a single-punch machine. However, its flow behaviour had to be improved by including 0.5% Aerosil(R) 200 as shown by tablet weight uniformity data. Further evaluation by Heckel analysis showed that isomalt exhibited plastic behaviour and underwent elastic recovery primary in the die. Its dilution potential was examined using powdered paracetamol. Acceptable tablets were produced up to 30% drug dilution, but the tensile strength values were reduced, disintegration time and friability increased as expected. Drug dissolution profiles showed a decreasing dissolution rate with the increase of compression force and drug concentration, but considerable improvement was noted when a disintegrant was included. The physical characteristics of the tablets were relatively stable after half a year storage at different humidities as a result of the low hygroscopicity of isomalt.

Cariogenic Agents↗
PubMed1999

Influence of the formulation composition on the in vitro characteristics of hot stage extrudates.

The aim of this study was to evaluate the influence of the formulation composition on the characteristics of starch based hot stage extrudates in order to obtain high quality and high efficacy matrices for controlled drug delivery. Their characteristics were compared to those of a reference formulation, for which in vivo data were available. The influence of the starch type, the plasticizer and the lubricant were investigated. The extrudates were produced with a twin screw co-rotating extruder equipped with a twin screw powder feeder and a 3 mm cylindrical die. The extrudates were manually cut and dried for 48 h at 60 degrees C prior to analysis. They were characterized by Karl Fischer titration, Hg-porosimetry, 4-point bending and dissolution testing. Changing the formulation composition did not affect the water content or the porosity of the extrudates but had an influence on their mechanical strength and dissolution profiles. These characteristics were particularly dependent on the plasticizer and lubricant concentration used and on the nature of the starch component and the lubricant. Expansion, depending on starch conversion and amylose-lipid complex formation, played a major role in the explanation of the results obtained. All the formulations tested showed a slow drug release profile in vitro. However, the differences with the reference formulation--which was tested in vivo in earlier work--were probably too small to give a distinct improvement of its in vivo behaviour.

Chemistry, Pharmaceutical↗
PubMed1999

Bioavailability of starch based hot stage extrusion formulations.

The aim of the study was to develop a starch based hot stage extrusion formulation for controlled drug delivery and to evaluate its in vivo behavior. The extrusion mixture consisted of 53% corn starch as the matrix forming agent, 15% sorbitol as a plasticizer, 30% theophylline monohydrate as the model drug and 2% glyceryl monostearate as a lubricant. The extrudates were produced by means of a corotating twin screw extruder of APV Baker equipped with a twin screw powder feeder and a 3-mm cylindrical die. During extrusion 20% water (based on the wet mass) was added to the powder mixture. The extrudates were dried in an oven at 60 degrees C during 48 h, cut and filled out in hard gelatine capsules, in a way that the content of two capsules corresponded with a dose of 300 mg anhydrous theophylline. The dissolution profile of the experimental dosage form was retarded with a drug release of around 80% in 8 h. The in vivo behavior of the experimental formulation was evaluated in a randomized crossover design study (n=8) with a commercially available multiple unit sustained release product as the reference formulation. The plasma samples were analyzed by a validated HPLC-UV method with solid phase extraction for the sample preparation. It was clear that the experimental formulation exhibited sustained release behavior, but that it performed less well than the multiple unit dosage form.

Adult↗
PubMed1999

Pharmacokinetics of florfenicol after treatment of pigs with single oral or intramuscular doses or with medicated feed for three days.

The pharmacokinetics of florfenicol, a structural analogue of thiamphenicol, were studied in six pigs after single oral and intramuscular doses of 15 mg/kg bodyweight, and after feeding them with medicated feed containing 250 mg/kg for three days, a concentration which provided approximately the same dose rate of the drug. The oral doses contained a specially prepared pelleted formulation of the drug. The bioavailability of the drug was similar for the oral and intramuscular doses. Florfenicol was absorbed rapidly from the feed and its concentration in plasma remained between 2 and 6 microg/ml - above the minimum inhibitory concentration values for common pig pathogens - during the three days.

Administration, Oral↗
PubMed1999

Stability and compatibility of morphine.

Morphine is a widely used analgesic for the treatment of severe cancer pain. For a large number of terminally ill patients oral administration is no longer possible and morphine is administered parenterally using portable pumps allowing comfortable treatment of the patient at home. In this situation the storage of pre-filled reservoirs and/or the administration over a longer period of time are daily practices and require data on the stability of morphine solutions. As most of these patients suffer from several other symptoms, the administration of admixtures with other drugs is common and requires information on the compatibility of morphine. Morphine degrades in aqueous solutions with the formation of mainly pseudomorphine, to a lesser extent morphine-N-oxide and probably apomorphine. From the study of the kinetics of morphine degradation it was concluded that the degradation of morphine is accelerated in the presence of oxygen and at higher pH of the solution, whereas temperature and light have only a minor influence on the degradation rate. The data reported on the stability of morphine infusion solutions kept under ambient conditions indicated that oxygen, light, the type of reservoir, the type of diluent, the salt form and the concentration of morphine do not affect the stability of morphine solutions stored for up to 3 months. Morphine solutions should preferably be stored at room temperature in order to avoid precipitation at low temperatures and water evaporation at higher temperatures causing increase in morphine concentration when stored in polymer reservoirs. Analyzing the data available on the compatibility of morphine infusion solutions revealed that differences in the formulation of the drug solutions (drug concentration, salt form, type and concentration of additives) and diluent, as well as temperature and order and ratio of mixing might affect the compatibility. Only few reports provide all necessary information, limiting the information useful for daily practice. Moreover, the majority of the compatibility studies are performed in intensive care units, where other drugs and other concentrations of morphine are required than in palliative care settings, limiting its merit for this sector.

Analgesics, Opioid↗
PubMed1999

The formulation and stability of erythromycin-benzoyl peroxide in a topical gel.

The combination of benzoyl peroxide and erythromycin is used for the local treatment of acne and available as a commercial preparation. Because of the stability problems of erythromycin an extempore preparation is required. The influence of storage temperature and non active ingredients on the stability of benzoyl peroxide and erythromycin in topical gel preparations for extempore compounding is described. A microbiological and an HPLC method were used to determine the erythromycin and the benzoyl peroxide concentrations, respectively. For a formulation compounded with hydroxyethylcellulose no stability problems were observed. For the formulation containing Carbopol 940, the levels of erythromycin varied over a wide range due to precipitation and aggregation of the drug during compounding.

Acrylic Resins↗
PubMed1999

Compatibility and stability of ternary admixtures of morphine with haloperidol or midazolam and dexamethasone or methylprednisolone.

The concentration range over which compatible admixtures of morphine hydrochloride with haloperidol lactate (Haldol) or midazolam hydrochloride (Dormicum) and dexamethasone-21-sodium phosphate (Decadron and Decadron Pack) or methylprednisolone-21-sodium succinate (Solu-Medrol) can be prepared was determined by visual evaluation of the solutions at 22 degrees C. The compatibility was evaluated for admixtures prepared in a ratio morphine hydrochloride (D1)/drug 2 (D2)/drug 2 (D3) in a ratio 10/1/1 to 10/1/10 (v/v/v). The solutions of morphine hydrochloride used were 10, 20, 30, 40 and 50 mg/ml prepared in water and isotonized with sodium chloride or dextrose. The drug solutions were used undiluted and diluted 1/5 (v/v) in water. All admixtures were prepared by adding the corticosteroid as D2 and as D3 in order to evaluate the influence of the order of mixing on the compatibility. The stability of the drugs in the compatible admixtures was evaluated during storage for 28 days at 22 degrees C and protected from light. Visual inspection, high performance liquid chromatography (HPLC) analysis, pH and osmolality determinations were performed. For each drug combination incompatibility was observed with increasing ratio and/or concentration of the drug solutions. Within the range of compatibility the concentrations of the three drugs could be increased so to allow adequate symptom control with all drug combinations. For a similar admixture a higher concentrations of corticosteroid could be obtained using dexamethasone-21-sodium phosphate versus methylprednisolone-21-sodium succinate and a higher concentration of dexamethasone-21-sodium phosphate could be obtained without incompatibility using Decadron Pack versus Decadron. The admixtures for which the stability was evaluated were stable for 28 days (> 95% of the initial concentration). None of these admixtures showed any visual changes during storage, except for some of the admixtures prepared using undiluted Decadron, in which small crystals were seen after 1-28 days. The initial pH of the admixture ranged from 3.99 to 6.06 and varied less than 0.10 during storage. The initial osmolality of the admixtures ranged from 170 to 323 mOsm/kg and remained almost constant during storage.

Chromatography, High Pressure Liquid↗
PubMed1999

Direct HPLC analysis of ketoprofen in horse plasma applying an ADS-restricted access-phase.

Making up part of the unique family of restricted access materials (RAM) the Lichrospher ADS (alkyl-diol silica) sorbents have been developed as special packing materials for precolumns used for LC-integrated sample processing of biofluids. The advantage of such phases consists of direct injection of untreated biological fluids without sample clean-up and elimination of the protein matrix together with an on-column enrichment. The plasma samples, with internal standard phenacetin added (not essential), were brought onto the precolumn (C-18 ADS, 25 micron, 25 x 4 mm i.d.) using a phosphate buffer, 0.1 M, pH 7.0. After washing with the buffer, the ADS column was backflushed with the mobile phase phosphate buffer 0. 05 M pH 7.0: acetonitrile (80:20), thus transporting the analytes onto a reversed-phase column Ecocart 125-3 HPLC cartridge with a LiChrocart 4-4 guard column, both packed with LiChrospher 5 micron 100 RP-18; after separation detection was performed in UV at 260 nm. Essential features of the method include the novel precolumn packing, the absence of sample pretreatment, a quantitave recovery, good precision and accuracy, as well as a considerable reduction of analysis time compared to conventional manual methods applied in bioavailability studies.

Animals↗
PubMed1999

Gastropods as an evaluation tool for screening the irritating potency of absorption enhancers and drugs.

PURPOSE: The objective of this study was to develop a simple alternative test using naked snails (slugs) for screening the irritating potency of chemicals on mucosal surfaces. METHODS: The effect of various absorption enhancers and two beta-blocking agents on the mucosal tissue was determined from the total protein and lactate dehydrogenase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs caused by the treatment were measured. RESULTS: According to the effects on the mucosal epithelium of the slugs the following rank order of increasing toxicity was established: PBS, HP-beta-CD (5%), beta-CD (1.8%) and oxprenolol hydrochloride (1%) < DDPC (1%) < STDHF (1%) < BAC (1%), SDC (1%) and propranolol hydrochloride (1%). The results of the present study are in agreement with other studies using the same compounds on other models. CONCLUSIONS: The results of this study indicated the mucosa of slugs can serve as a primary screening tool for the evaluation of chemicals on mucosal surfaces. By simply measuring mucus production and weight loss reliable toxicity information can be obtained. This demonstrates rapid screening tests can be carried out using simple toxicity endpoints.

Absorption↗
PubMed1999

Bioavailability of racemic ketoprofen in healthy horses following rectal administration.

Ketoprofen (KTP) is a chiral non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class, approved by the FDA for the allevation of pain associated with musculoskeletal disorders in horses. The present study was designed to examine the bioavailability of ketoprofen enantiomers after rectal administration of the racemate to healthy horses. One gram of racemic ketoprofen was injected intravenously and administered rectally as a fat based suppository in a cross-over design study (n = 4). Blood samples were analysed for KTP enantiomers using HPLC. After IV administration, the S(+) enantiomer concentrations in plasma were higher than the R(-) enantiomer concentrations and the AUC(0-12 h) for the S(+) enantiomer was significantly higher than for the R(-) enantiomer. Following rectal administration C(max) and AUC(0-12 h) were significantly higher for the S(+) than for the R(-) enantiomer. Bioavailability after rectal administration was low. Since there was no significant difference in bioavailability between the two enantiomers, it is assumed that no pre-systemic inversion from R(-) to S(+) occurred after rectal administration of racemic KTP to horses.

Administration, Rectal↗
PubMed1999

Evaluation of the emulsifying properties of some cationic starches.

Different cationic potato, maize, and waxy maize starches were evaluated for their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a concentration ranging from 1% to 5% (w/w) were prepared and characterized by droplet size and viscosity measurements, and the stability was evaluated visually and by electrical conductance measurements. None of the cationic potato, waxy maize starches, and maize starches with a low degree of substitution (DS) showed adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C [symbol: see text] bond 05914, 2% and 5% w/w; C [symbol: see text] bond 05907, 5% w/w) and pregelatinized (C [symbol: see text] bond 12504, 5% w/w) cationic maize starches with high-DS were visually stable. The initial mean droplet volume diameter of the emulsions prepared with these cationic starches in a 5% (w/w) concentration was similar and ranged from 2.40 to 2.84 microns; however, there was an important difference in droplet size distribution. The droplet size distribution of the emulsions prepared using the non-pregelatinized high-DS cationic starches was markedly narrower than in the case of the emulsions prepared using the pregelatinized high-DS cationic starches. The droplet size of the emulsions remained almost constant during 120 days of storage. Visual inspection and electrical conductance measurements showed that these emulsions were stable for at least 120 days.

Cations↗
PubMed1999

Stability of freeze-dried tablets at different relative humidities.

The purpose of the study was to evaluate the stability of two different freeze-dried tablet formulations at different relative humidities (RHs). The tablets contained 25 mg hydrochlorothiazide (HCT) as a model drug and were prepared by freeze-drying a suspension and an oil-in-water (o/w) emulsion. Formulation A was a rapidly disintegrating tablet and consisted of 80 mg of maltodextrine DE38; 8 mg of polyethyleneglycol (PEG 6000), 8 mg of xanthan gum, and 25 mg of HCT. Formulation B was a lyophilized dry emulsion tablet that consisted of 160 mg of Miglyol 812, 80 mg of maltodextrin DE38, 16 mg of methylcellulose (Methocel) A15LV, and 25 mg of HCT. Tablets were packaged in different packing materials: polyvinylchloride (PVC)/aluminum blister packs, PVC-polyvinylidenechloride (PVDC)/aluminum blister packs, closed containers with a dessicant tablet, and open containers. The tablets were stored at three relative humidities (45%, 60%, and 85% RH) and were characterized on mechanical strength, residual moisture, porosity, content uniformity, and scanning electron microscopy (SEM) during a period of 6 months. After 1 month at 60% and 85% RH, a strong increase in moisture content (from 2.7% to 6.8%) was seen for the tablets packed in the open and closed containers and for the PVC/aluminum blistered tablets. This increase was higher for formulation A compared to formulation B since B contained 160 mg of triglycerides and was more hydrophobic. This increase in water content was correlated with a decrease in mechanical strength. The tablets also showed a change in microstructure and porosity. At a moisture content of 7.2%, formulation A showed a structural "collapse" since water acts as a plasticizer for the amorphous glass, lowering the glass transition temperature Tg. This phenomenon even occurred in PVC/aluminum blister packs at 85% RH. The structural collapse was associated with a complete loss of microstructure as detected by porosimetric analysis and SEM. For the PVC-PVDC/aluminum blistered tablets, the increase in moisture content and decrease in mechanical strength at 85% RH occurred much slower, and the water uptake and strength loss were less intensive. No significant breakdown of HCT could be observed in both formulations with all of the packing materials. Packaging of freeze-dried tablets with PVC/aluminum blister packs, PVC/PVDC/aluminum blister packs, or closed containers did not offer protection against moisture uptake, mechanical strength loss, and structural collapse.

Aluminum↗