Biomedical subjects

P Paronen

Publications and source records attributed to P Paronen.

45 records · Page 3Linked to original sources

PubMed1990

Effect of central muscle relaxants on single-dose pharmacokinetics of peroral paracetamol in man.

Paracetamol (acetaminophen) at a single, 160-450 mg dose was given perorally in combination with central muscle relaxants (CMRs) carisoprodol (200 mg), chlormezanone (100 mg) or orphenadrine (35 mg) in a double-blind, randomized, cross-over study in 10 healthy volunteers. The pharmacokinetic parameters of paracetamol remained unaltered in the presence of the CMRs as compared with those observed after paracetamol without additives, in spite of nearly twenty-fold differences in the dissolution rate between the products. Paracetamol is absorbed mostly in the duodenum, and therefore there is enough time for even the slowly dissolving tablets to release the active principle before the gastric contents are transferred to the area of paracetamol absorption. Some CMRs are anticholinergic compounds and may affect intestinal motility. Our results show, however, that CMRs do not significantly alter the pharmacokinetics of paracetamol, and presumably the antipyretic or analgetic efficacy of paracetamol is not impaired when combination formulations of paracetamol and CMRs are used.

Acetaminophen↗

PubMed1990

In vivo evaluation of the new multiple dose powder inhaler and the Rotahaler using the gamma scintigraphy.

Deposition of 99mTc-labelled particles of disodium cromoglycate in the respiratory tract was evaluated after inhalation from two dry powder inhalers. The inhalers tested were a new multiple dose powder device (Chiesi Farmaceutici) and the Rotahaler powder device (Glaxo). Fractional deposition in the whole lung area, the upper respiratory passages and the stomach, as well as in the inhaler, was measured using a gamma camera. Ten healthy volunteers participated in the inhalation test. The mean, whole lung deposition of the inhaled disodium cromoglycate particles was about 9 per cent of the dose for the both devices. The deposition patterns of the inhaled drug doses in the lung area given by the devices were, however, clearly different. The Chiesi powder inhaler was more efficient in dispersing the drug particles into the therapeutically important alveolar regions of the lungs. The fraction of the dose retained in the inhaler was significantly higher for the Rotahaler than for the Chiesi powder device. On the other hand, the deposition in the upper passages was somewhat larger for the Chiesi device than for the Rotahaler. According to the deposition results of this study, a new multiple dose powder inhaler can be useful in inhalation therapy.

Animals↗

PubMed1990

Pharmacokinetics of ibuprofen in man: a single-dose comparison of two over-the-counter, 200 mg preparations.

The pharmacokinetic properties of two 200 mg, over-the-counter (OTC) ibuprofen preparations were compared in a randomized crossover study on ten healthy volunteers. After 2 times 200 mg single dose, one preparation produced peak plasma ibuprofen concentration 30.0 +/- 2.1 micrograms/ml at 1.6 h and the other preparation 23.2 +/- 1.9 micrograms/ml at 2.3 h (p less than 0.05). There was no statistically significant difference between the preparations in the bioavailability of ibuprofen. OTC ibuprofen preparations are mainly used for acute indications, such as fever or headache. In these cases, rapid absorption and high concentrations of active ingredient are desirable properties, especially when the amount of drug is relatively low. Therefore, the pharmacokinetic differences between these preparations may be therapeutically significant.

Adult↗

PubMed1989

Evaluation of a novel cellulose powder as a filler-binder for direct compression of tablets.

A novel form of cellulose powder was evaluated as a filler-binder in tablets. The particle, powder, flow and binding properties of this experimental cellulose material were compared with those of two commercial microcrystalline celluloses, Avicel PH 101 and Emcocel. The effect of various storage conditions on the physical stability of tablets compressed from celluloses was also evaluated. The particle size and shape of experimental cellulose powder differed markedly from those of microcrystalline celluloses. Experimental cellulose contained mainly large and roughly spherical agglomerates of particles, among which were few smaller regularly shaped particles. Because of spherical particle shape, the experimental cellulose powder flowed better than microcrystalline celluloses, which consisted of much more irregularly shaped particles. Experimental cellulose formed stronger tablets than microcrystalline celluloses. It also acted more effectively than microcrystalline celluloses as a binding material in tablets containing poorly compressible ascorbic acid and acetaminophenone. This may be due to the extensive surface area of the particles of experimental cellulose powder. The specific surface area of this material was over 50 times as great as that of microcrystalline celluloses. This indicates an extremely porous structure of cellulose agglomerates. Tablets containing experimental cellulose powder were able to resist a permanent loss in tablet strength at different storage conditions better than tablets containing microcrystalline celluloses. According to the results of this study an experimental agglomerated form of cellulose powder is a very advantageous material as a filler-binder for direct compression of tablets.

Cellulose↗

PubMed1989

Pharmacokinetics and acute side-effects of nifedipine given as slow-release tablets or liquid-filled capsules.

The pharmacokinetics and acute adverse effects of nifedipine were studied in a cross-over, single dose (20 mg) study on ten healthy young volunteers. From the liquid-filled capsules, nifedipine was absorbed rapidly (tmax at 30-40 min). From tablets, the peak concentration was 79-88% lower and occurred 74-133 min after ingestion; also the bioavailability was lower, as indicated by on average 39% lower area under curve values after tablets. All the volunteers experienced side-effects: the most common (nine out of the ten) and the most intense was headache. One volunteer withdrew because of unbearable vomiting and headache. Also others felt nauseous (six out of nine who continued) and four of them vomited. After tablets, the dizziness was markedly less than after capsules, but the more slowly-appearing symptoms such as headache and nausea were similar after both types of drug products. By using slow-release tablets instead of capsules it seems possible to avoid some side-effects of nifedipine, but this benefit is gained at the expense of bioavailability.

Adult↗

PubMed1984

Xylan--a possible filler and disintegrant for tablets.

Xylan, a novel possible adjuvant for tablets was tested and compared with modified starch, Sta-Rx 1500, for weight variation, strength and disintegration of tablets. There was no remarkable difference in weight variation between the tablets of the corresponding compositions. The tablets containing xylan were stronger and disintegrated more rapidly than those containing modified starch.

Adjuvants, Pharmaceutic↗

PubMed1983

Compressional characteristics of four starches.

Compression data about barley, corn, potato and wheat starches were obtained by two methods: the ejected tablet method and the tablet-in-die-method. These data were analysed using the Heckel and the Cooper-Eaton equations. The Heckel equation appeared to be the more sensitive in distinguishing the various stages during the compression. Die filling and rearrangement processes for the starches were especially dependent on particle size and shape and thus on contact area between particles. Densification of large starch particles (potato starch) owed more to die filling and less to rearrangement. Densification of small particles (corn starch) was the reverse. Starch having a wide particle size distribution (wheat) or an irregular particle shape (barley) underwent a relatively small amount of densification as a result of die filling and a relatively great amount of densification because of rearrangement of particles during tableting. The tendency of the starches to total and pure plastic deformation was dependent on particle size, size distribution and particle shape. Corn starch was the most prone to plastic flow with only little elastic recovery. Potato starch also flowed plastically with ease. Barley and wheat starches were the more elastic.

Drug Compounding↗

PubMedDate not supplied

Microencapsulation of indomethacin by gelatin-acacia complex coacervation in the presence of surfactants.

Gelatin-acacia microcapsules containing indomethacin were prepared by a complex coacervation method. To improve the wetting of hydrophobic core material different surfactants, cationic benzalkonium chloride, anionic sodium lauryl sulphate (SLS) or non-ionic polysorbate 20, were used. The effects of surfactants on microencapsulation were investigated at concentrations below, at and above their critical micelle concentration (CMC) using three different stirring speeds (200, 310 and 420 rpm). A considerable fraction of the core was leached out during the dehydration of microcapsules with isopropanol when the capsules were prepared without surfactant, and especially with SLS. SLS was noted to be an unsuitable surfactant for this process of microencapsulation, and this was considered to be due to ionic complexes, solubilization of gelatin and too-effective spreading of small coacervate droplets. Benzalkonium chloride enhanced encapsulation at concentrations below and at CMC, but above CMC the encapsulation was slightly decreased due to too-effective spreading of coacervate. Polysorbate 20 enhanced encapsulation with all the concentrations allowing for the formation of intact-walled microcapsules. All the microcapsules reduced in size with increasing stirring speed. The two lowest concentrations of benzalkonium chloride and all the concentrations of polysorbate 20 increased microcapsule size due to a greater amount of the colloids being available in formation of thicker walled microcapsules. The dissolution of unencapsulated indomethacin was very slow, but the drug was released quickly from all the microcapsules whether or not any type of surfactant was used. A hydrophilic wall of gelatin-acacia microcapsules in itself ensured quick wetting of hydrophobic indomethacin.

1-Propanol↗

PubMedDate not supplied

The uptake of clodronate (dichloromethylene bisphosphonate) by macrophages in vivo and in vitro.

Clodronate (dichloromethylene bisphosphonate) accumualtes extensively in the bone by binding to apatite crystals. We found recently that the drug also accumulates in the spleen and, to a lesser extent, in the liver of mice and rats. In the present study, the role of macrophages in soft tissue accumulation was studied in mice by autoradiography and macrophage-depleting techniques, and also by isolated rat peritoneal macrophages. The localization of [14C]clodronate in mouse spleen showed that the drug concentrates in the marginal zone between the white and red pulp, which is known to be rich in macrophages. Pretreatment of mice with pure clodronate did not change the accumulation of [14C]clodronate in the spleen. However, when splenic and hepatic macrophages were eliminated by the liposome-encapsulated clodronate, only a weak [14C]clodronate accumulation occurred in these organs. Isolated macrophages did not take up free [14C]clodronate, but the addition of ferrous iron to the incubate resulted in the uptake of 14C activity by macrophages. They were probably stimulated by the insoluble clodronate-iron complex. The results suggest that 1) macrophages are involved in the accumulation of clodronate in the spleen and liver, and 2) combination of clodronate with extracellular iron is a prerequisite for the activation of macrophages to take up the drug complex. Since the spleen and, to a lesser extent, the liver are rich in iron released from destroyed red cells, accumulation of clodronate takes place in these organs.

Animals↗