Biomedical subjects

S Negro

Publications and source records attributed to S Negro.

11 recordsLinked to original sources

PubMed2006

Vitamin A palmitate and aciclovir biodegradable microspheres for intraocular sustained release.

The aim of this study was to obtain a prolonged release of Vitamin A palmitate (RAP) and aciclovir from biodegradable microspheres for intraocular administration with an antiviral action and to be capable of preventing the inherent risks of intravitreal administration. The RAP effect on the microsphere characteristics was also studied. Poly(D,L-lactic-co-glycolic) acid microspheres were prepared by the solvent evaporation method. Different quantities of aciclovir (40-80 mg) and RAP (10-80 mg) were added to the internal phase of the emulsion. Microspheres were analysed by scanning electron microscopy, which revealed a spherical surface and a porous structure, and granulometric analysis that showed an adequate particle size for intraocular administration. The aciclovir loading efficiency increased when Vitamin A palmitate was added. Differential scanning calorimetry detected no differences in the polymer glass transition temperature and the aciclovir melting endotherm in all formulations. The release of aciclovir during the first days of the in vitro assay was improved with respect to microspheres without RAP. The microspheres showed a constant release of aciclovir and RAP for 49 days. Best results were obtained for microspheres prepared with 40 mg aciclovir, 80 mg RAP and 400mg polymer. A dose of 4.74 mg of microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses' treatment in an animal model and would reduce the intravitreal adverse effects. The injectability of a suspension of microspheres in isotonic saline solution resulted appropriate for its injection through a 27 G needle.

Acyclovir↗

PubMed2006

Ménage à trois on Macquarie Island: hybridization among three species of fur seal (Arctocephalus spp.) following historical population extinction.

Human-induced changes to natural systems can cause major disturbances to fundamental ecological and population processes and result in local extinctions and secondary contacts between formerly isolated species. Extensive fur seal harvesting during the nineteenth century on Macquarie Island (subantarctic) resulted in extinction of the original population. Recolonization by three species has been slow and complex, characterized by the establishment of breeding groups of Antarctic and subantarctic fur seals (Arctocephalus gazella and Arctocephalus tropicalis) and presumed nonbreeding (itinerant) male New Zealand fur seals (Arctocephalus forsteri). One thousand and seven pups from eight annual cohorts (1992-2003) were analysed using mitochondrial control region data (RFLP) and 10 microsatellite loci to estimate species composition and hybridization. Antarctic fur seals predominated, but hybridization occurred between all three species (17-30% of all pups). Involvement of New Zealand fur seals was unexpected as females are absent and males are not observed to hold territories during the breeding season. The proportion of hybrids in the population has fallen over time, apparently owing to substantial influxes of pure Antarctic and subantarctic individuals and non-random mating. Over 50% of New Zealand hybrids and 43% of Antarctic-subantarctic hybrids were not F(1), which indicates some degree of hybrid reproductive success, and this may be underestimated: simulations showed that hybrids become virtually undetectable by the third generation of backcrossing. While human impacts seem to have driven novel hybridization in this population, the present 'time slices' analysis suggests some biological resistance to complete homogenization.

Alleles↗

PubMed2005

Morphine, haloperidol and hyoscine N-butyl bromide combined in s.c. infusion solutions: compatibility and stability. Evaluation in terminal oncology patients.

The administration of drugs by subcutaneous infusion is routinely practiced in palliative medicine for the management of patients who are no longer able to take oral medication. It is common for two or more drugs to be combined in subcutaneous solutions. The combination of an opioid with other drugs (haloperiol lactate and hyoscine N-butyl bromide) can be very valuable. Unfortunately, the compatibility and stability of morphine hydrochloride, haloperidol lactate and hyoscine N-butyl bromide combined in the same solution has not yet been determined. Therefore, this study examined the stability of ternary solutions containing morphine HCl, haloperidol lactate and hyoscine N-butyl bromide at different dose ranges. Twelve different solutions were assessed for 15 days after preparation in polypropylene syringes using 0.9% saline as diluent. Triplicate syringes were stored at 25 degrees C. HPLC was the analytical technique used to measure morphine HCl, haloperidol lactate and hyoscine N-butyl bromide. Initial concentration ranges were 1.67-10.0 mg/ml for morphine HCl, 0.417-0.625 mg/ml for haloperidol lactate and, 5.0-6.67 mg/ml for hyoscine N-butyl bromide. All three drugs were very stable (>92.5%) when stored at 25 degrees C. The clinical performance of the admixture was retrospectively assessed in 21 terminal oncology patients. Total symptom control was achieved in 17 out of 21 patients with very good local tolerance.

Aged↗

PubMed2005

Interactions of anti-infectives: a review.

Drug interactions can be beneficial and valuable, but their consequences are usually adverse/undesirable, thus compromising the efficacy of drugs and enhancing their toxicity. Interactions can be divided into pharmaceutical incompatibilities, and pharmacokinetic and pharmacodynamic interactions. Unexpected drug responses can result from drug-excipient incompatibilities or erroneous technological processes. Pharmacokinetic interactions can affect the processes of drug absorption, distribution, metabolization and excretion. Pharmacodynamic interactions occur when the effects of one drug are changed by the presence of another drug at its site of action; such interactions are classified as synergistic and antagonistic. The clinically most relevant drug interactions following this classification and regarding the use of anti-infectives are reviewed. Knowledge, research and discussion of drug interactions will assist in giving the patient optimal care.

Anti-Infective Agents↗

PubMed2004

Optimisation of aciclovir poly(D,L-lactide-co-glycolide) microspheres for intravitreal administration using a factorial design study.

The purpose of this work was to obtain an optimised long-term aciclovir PLGA microspheres formulation for intravitreal administration to minimise, as much as possible, the dose of microspheres to be administered with a suitable particle size for its injection through a 27G needle in a single dose. Microspheres were prepared by the solvent evaporation method. To obtain the optimum formulation a two-factor five-level central rotatable composite 2(2) + star design was employed. The independent variables were aciclovir and gelatin (added to the external phase of the emulsion). The dependent variables were the yield of production (%), the encapsulation efficiency (%), the initial burst release (%), the cumulative amount released from 1 to 14 days and the amount of aciclovir at the end of the release assay (microg aciclovir/mg microspheres). The best formulation according to the studied variables was (0,0), prepared with 80 mg of aciclovir and 80 mg of gelatin. This formulation showed good yield of production (70.14 +/- 3.72 %) and encapsulation efficiency ( 70.77 +/- 2.62 %), and released the drug at a constant rate for 63 days with a mean release constant of 1.73 +/- 0.08 microg/day per mg microspheres. The selected formulation reduces a 40% the dose of microspheres to be administered through a 27G needle with respect to previous studies.

Acyclovir↗

PubMed2004

Determination of vitamin E acid succinate in biodegradable microspheres by reversed-phase high-performance liquid chromatography.

A simple, rapid, and reproducible reversed-phase high-performance liquid chromatographic (HPLC) method is applied to the routine assay of vitamin E acid succinate in biodegradable microspheres. Vitamin E acid-succinate-containing poly-(D,L-lactic-co-glycolic acid) microspheres are prepared by the solvent evaporation method. The starting drug-polymer ratio is 1:10 (w/w) and the total amount of drug and polymer processed is always 440 mg. The content of vitamin E acid succinate in the microspheres is evaluated by HPLC. Chromatography is carried out isocratically at 25 degrees C +/- 0.5 degrees C on an Extrasil ODS-2 column with a mobile phase composed of methanol-water (97:3, v/v) (pH 5.6) at a flow rate of 2 mL/min and UV detection at 284 nm. Parameters such as linearity, limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery, specificity, and ruggedness are studied as reported in the International Conference on Harmonization guidelines. The stability of vitamin E acid succinate is also studied with satisfactory results after 48 h at 25 degrees C. The method is selective and linear for drug concentrations in the range 15-210 micro g/mL. The LOQ and LOD are 15 and 3 micro g/mL, respectively. The results for accuracy studies are good. Values for coefficient of variation for intra- and interassay are 2.08% and 2.32%, respectively. The mean percentage of vitamin E acid succinate in the recovery studies is 99.52% +/- 0.81%. The mean loading efficiency for microspheres is 96.53% +/- 1.31%.

Biodegradation, Environmental↗

PubMed2001

Comparative study of the dissolution profiles of a commercial theophylline product after storage.

The purpose of this work was to study the effect of storage time and temperature on the in vitro release kinetics of a commercial sustained-release dosage form of theophylline, at different pHs of the dissolution medium. The formulation was stored at 35 degrees C for 16 months and at 45 degrees C for 8 months, with a relative humidity of 60%. The in vitro release tests were performed at pHs 2, 4, 6 and 7.4. The mean values of the transport coefficient n, were close to 0.5 in all the conditions tested, which indicates that the transport system is not modified after storage of the formulation at 35 degrees C and 45 degrees C. The mean values of the dissolution rate constant ranged from 0.036 to 0.043 min(-n), under all the conditions tested. Significant differences (alpha = 0.05) were found between pHs 2, 4 and 6, 7.4 for all the model-independent parameters studied. When the formulation was kept at 35 degrees C for 16 months, the mean percentage of drug dissolved at 8 hours was 25.61% (pHs 2, 4) and, 36.12% (pHs 6, 7.4), representing a 26% and 24% reduction, respectively. Similar results were obtained after storing the formulation at 45 degrees C for 8 months, corresponding to 33.3% (pHs 2, 4) and, 22.5% (pHs 6, 7.4) diminution, respectively. The values of the similarity factor, f2, obtained were lower than 50, which indicates the lack of similarity among the dissolution profiles, after storing the formulation under the experimental conditions tested.

Delayed-Action Preparations↗

PubMed1991

Dissolution kinetics of bezafibrate in two solid forms for oral administration.

The dissolution kinetics of two solid and oral formulations of bezafibrate have been studied. These preparations are available in the Spanish market. Both of them are tablets, one conventional-release (A) and the other slow-release formulation (C). Dissolution studies have been performed using the system proposed by the USP XXI. The solubility of the drug was determined in each release medium at 37 degrees C. The results indicate that the sink conditions were not satisfied. The evaluation of the dissolution rate-kinetics is performed by three different mathematical approaches. Strong differences in its "in vitro" behaviour were found.

Bezafibrate↗

PubMed1991

In vitro evaluation of the dissolution rate of crystalline suspensions destined to intramuscular administration.

The aqueous suspensions for intramuscular administration belong to the group of the dosage forms, that have a sustained release behaviour. These are based on the low aqueous solubility of the administered molecule whose aqueous suspensions form a depot in the muscular tissue which controls the absorption. The assays performed previously with two molecules of these characteristics have shown the inability of the habitual methods used for evaluating the dissolution rate of a drug, to determine the possible behaviour of these drugs in a definite and concrete formulation. For this reason, we have designed and developed a new method which allows us to support future processes, such as agglomeration and, possibly, cyst forming, that could be developed "in vivo". In this way, a more reliable prediction of the efficiency of inefficiency of this kind of formulation will be possible. Tha validity of our system has been studied with three formulations. Two of them were sustained release cefazolin molecules showing agglomeration problems "in vivo" and the other one a commercial penicillin-G benzathine commercial with a great efficacy demonstrated in habitual clinical practice.

Cefazolin↗

PubMed1990

Pharmacokinetics of cefroxadine after infusion to healthy volunteers.

The pharmacokinetics of cefroxadine in healthy human volunteers was studied in plasma and urine, after an infusion administration of 1 g of this drug for 0.5 h. Blood and urine samples were microbiologically quantified by diffusion on solid gelose using Bacillus Subtilis ATCC 6633 as the test organism. Plasma and urine profiles were fitted to a reduced two-compartment model not having inactivating biotransformation as a route of elimination. The parameters of distribution for this model show a rapid disposition (t1/2 alpha = 0.28 h) and an average volume of the central compartment of 0.15 +/- 0.04 l/kg (range 0.20-0.09). The dominant terminal half-life (beta-phase) was 1.17 +/- 0.26 h (range 0.90-1.67). The total body volume 0.41 +/- 0.09 l/kg (range 0.30-0.52) indicates that there is no diffusion of the antibiotic into intracellular fluids of poorly perfused tissues due to its high elimination rate.

Adult↗

PubMedDate not supplied

Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery of aciclovir: influence of fatty and non-fatty additives.

Aciclovir (acicloguanosine) has been demonstrated to be effective in the treatment of intraocular pathologies such as herpes simplex virus retinitis and acute retinal necrosis. Although intravitreal injections have been used with fewer side-effects than intravenous administration, the risk of complications increases with the frequency of intravitreous injections. For this reason, a biodegradable drug-delivery system, such as microspheres, able to promote prolonged release of the drug, offers a good alternative to multiple intraocular administrations. In this work, aciclovir-containing poly (D,L-lactide-co-glycolide) microspheres were prepared by the solvent evaporation method. Seven additives were incorporated in the microspheres to modulate the in vitro release rate of the drug: four non-fatty substances (polyethylene glycol 300, polyethylene glycol 1500, hydroxypropyl methylcellulose and gelatin) and three fatty substances (isopropyl myristate, vitamin E and Labrafil M 1944 CS). Morphology of microspheres was evaluated by scanning electron microscopy. Granulometric analysis showed that particle size distribution was significantly influenced by the incorporation of additives. Loading efficiency decreased when fatty substances were added, whereas non-fatty additives promoted higher incorporation of the drug. Infrared and differential scanning calorimetry analyses indicated that microspheres prepared by the solvent evaporation process were not influenced by the type of additive used. In all cases, the initial burst resulted less than 5%. Additive-free microspheres showed a slow release within the first days, but when additives were incorporated, in general, the release rates of the drug were increased. Best release results were obtained for gelatin-containing microspheres. The release of aciclovir from these microspheres was adjusted to a zero-order kinetic from 1 to 49 days with a release constant of 1.13 microg/day/mg microspheres. A dose of 0.74 mg microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses (MIC 0.1 microg/ml) and 7.4 mg for varicella zoster virus (MIC 1 microg/ml) treatment in an animal model.

Acyclovir↗