PubMed Health⌕ Search

Biomedical subjects

L Montanari

Publications and source records attributed to L Montanari.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of skin permeability of sesquiterpenes of an innovative supercritical carbon dioxide Arnica extract by HPLC/DAD/MS.

Recently, a supercritical carbon dioxide dried extract of Amica flower, with a very high sesquiterpene content was developed. In view of using this extract in formulations for cutaneous application, the ability of sesquiterpenes to permeate the skin was evaluated by HPLC/DAD/MS using the following permeation enhancers: oleic acid (OA), dimethylsulfoxide (DMSO), lauroglycol, isopropyl myristate and Tween 80. A skin permeation study was performed using a modified Franz diffusion cell and the human stratum corneum and epidermis as membrane. Solutions of the enhancers were directly analysed after dilution with methanol or DMSO. A simple RP-HPLC-DAD-MS method for the quantification of the sesquiterpenes was developed and the method showed no interference with the other substances extracted from the skin and the permeation enhancers. The study evidenced that among the selected skin permeation enhancers, DMSO and OA canbe considered as good candidates to be used in preparations for cutaneous application.

Arnica↗
PubMed2003

Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects.

The beta- and gamma-irradiation effects on stability of microspheres made of poly(lactide-co-glycolide) 50:50 copolymer (PLGA) containing bupivacaine (BU) were studied. Microspheres containing 10, 25, and 40% w/w, respectively, of BU were prepared by spray drying and irradiated in air with beta- and gamma-irradiation at a dose of 25 kGy. Morphology (atomic force microscopy, particle-size analysis), physico-chemical characteristics (DSC and FT-IR spectroscopy), drug content and in vitro dissolution profile of microspheres were all determined; the stability of irradiated microspheres was evaluated over a 9-month period. The decrease of BU content in gamma-irradiated microspheres was almost always constant independent of the amount of BU per sample, therefore it was in inverse proportion to drug loading (range between 5 and 15%). BU release rate increased immediately after irradiation and increased slightly until 90 days of storage. As far as beta-irradiated microspheres are concerned, BU content decreased in a significant way (approximately 3%) only in microspheres containing 10% w/w of BU. Immediately after irradiation, drug release rate in beta-irradiated microspheres increased less than in the corresponding gamma-irradiated microspheres, and it did not change further over the following storage period. BU-loaded microspheres have been shown to be more stable against beta- than gamma-irradiation. AFM revealed that the surface roughness of the irradiated microspheres increases depending on irradiation. As such, if a parameter is quantifiable, it is proposed as a marker of degradation due to ionizing radiation.

Anesthetics, Local↗
PubMed2003

Polymethacrylate salts as new low-swellable mucoadhesive materials.

The sodium and potassium salts of the methacrylic copolymers Eudragit L100 and Eudragit S100 were prepared with the aim to develop new low-swellable mucoadhesive materials intended for the preparation of buccal dosage forms. The physico-chemical characterization of the copolymers and the corresponding sodium and potassium salts was performed by using Fourier-transform infrared (FT-IR) spectroscopy and thermal analysis. When ionization occurred, the carboxylic acid group absorption band (1730 cm(-1)) was replaced by another characteristic band at 1560 cm(-1). After salification the T(g) of the two polymers shifted towards higher values and it was not significantly influenced by the contraion nature. The intrinsic dissolution rate at infinite rotation speed (7.354<G( infinity )<9.196) was about 6- to 7-fold higher than that of a low nominal viscosity hydroxypropylmethylcelluloses (HPMC). Moreover, the Eudragit salts did not show an evident swelling layer and their dissolution is governed by erosion. The adhesion properties of these materials, evaluated by texture analysis, overlapped with those of Carbopol 934P. On the basis of the in vivo bioadhesion test, the prepared methacrylic salts can be considered interesting for the preparation of both buccal tablets and patches with good patient compliance due to their low swelling properties.

Algorithms↗
PubMed2002

Characterization of nifedipine solid dispersions.

The sublingual administration of nifedipine (NIF) is currently used in clinical practice. The sublingual administration of NIF solid dispersions (SD), by using a suitable dispenser, appears an interesting approach in the treatment of moderate and severe hypertensive emergencies. With this aim nine SD made of NIF and a low viscosity hydroxypropylmethylcellulose (HPMC) in different ratio were prepared by means of spray-drying technique and their structure was studied. Moreover, the drug dissolution properties from SD were verified. The characteristic peaks of crystalline NIF were not detectable by using the X-ray analysis when the NIF/HPMC ratios were lower than 50/50 w/w. In thermograms obtained from SD, the NIF melting endothermic peak disappeared when NIF/HPMC ratios were lower than 30/70 w/w; the experimental Tg values of SD were lower than the Tg values predicted by Gordon Taylor equation suggesting some type of non-ideality of mixing. In the SD FTIR spectra the NH stretching vibrations and the C=O stretch in esteric groups of NIF shift to free NH and C=O regions indicating the rupture of intermolecular hydrogen bond in the crystalline structure of NIF. The prepared SD improved the NIF dissolution rate in comparison with that of commercial NIF or NIF/HPMC physical mixtures. Moreover, the concentration of NIF in the dissolution medium increased decreasing the NIF content.

Administration, Sublingual↗
PubMed2002

Gamma irradiation effects and EPR investigation on poly(lactide-co-glycolide) microspheres containing bupivacaine.

The effects of gamma radiation on the stability of microspheres made of a polylactide-co-glycolide 50:50 copolymer (PLGA) and loaded with 40% bupivacaine (BU) were studied. The radiolysis mechanisms of BU and BU-loaded microspheres were investigated by using electronic paramagnetic resonance (EPR) analysis. Microspheres were prepared by means of a spray drying method. Gamma Irradiation was carried out in the open, at the dose of 25 kGy, by using a 60Co source. The stability of BU-loaded microspheres was evaluated over a 1-year period on the basis of drug content and dissolution profile. Non-irradiated microspheres were stable over the whole period under consideration. Immediately after irradiation the amount of BU released after 24 h from irradiated microspheres increased from 17 to 25%; in the following 3 months of storage it increased to about 35%, and then it kept constant for 1 year. Radicals generated by BU irradiation were identified by EPR analysis; the sensitivity to gamma radiation of BU was about four times lower than that of PLGA. Furthermore, the EPR spectra of loaded microspheres showed that the relative abundance of BU radicals plus PLGA radicals was proportionate to the electronic fractions of the components; this implies that no spin transfer BU/PLGA had occurred during gamma irradiation.

Alanine↗
PubMed2001

Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam.

This work was aimed at evaluating the effects of gamma irradiation on the stability of microspheres made of a poly(lactide-co-glycolide) copolymer (PLGA) and loaded with 15% w/w of clonazepam (CLO). The influence of CLO on PLGA radiolysis mechanisms and the identification of possible irradiation markers were also investigated. Microspheres were prepared by means of a spray-drying method. gamma Irradiation was carried out either under vacuum or in air, at a dose of 25 kGy, by using a 60Co source. The stability of CLO loaded microspheres was evaluated over a 6-month period on the basis of drug content and dissolution profile. Radiolysis mechanisms were investigated by using electronic paramagnetic resonance (EPR) analysis. The microspheres irradiated under vacuum were stable over the considered period of time. After irradiation in air, CLO release rate increased by approximately 10%, and did not change further in the following period of storage. The EPR analysis showed some radicals arising from both the polymeric matrix and the active ingredient. Polymer/CLO spin transfer reactions suggest that CLO had a radio-stabilising effect on the polymeric matrix. In the loaded microspheres, the intensity in time of the CLO radical signal is sufficient for its possible use as irradiation marker.

Calorimetry, Differential Scanning↗
PubMed2001

Development of patches for the controlled release of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the major secretory steroidal products of the adrenal gland. Some epidemiologic studies have found an association between low DHEA serum levels in patients and many important diseases. To prevent all such pathological conditions and, in any case, in aging, a DHEA supplementation has been proposed. DHEA shows a low oral bioavailability; taking the bioavailability obtained by the subcutaneous route as 100%, it was estimated that the potencies of DHEA by the percutaneous and oral routes were approximately 33% and 3%, respectively. Thus, transdermal patches could be considered a promising formulation as a continuous and controlled delivery of DHEA in replacement therapy is desired. With the aim of evaluating the effect of the matrix composition in terms of polymers and enhancers on the DHEA skin permeation flux, 10 types of monolayer self-adhesive patches containing 0.25mg/cm2 of active ingredient were designed. The matrices were based on three different acrylic copolymers: an acrylate-vinylacetate copolymer, a polyaminomethylmethacrylate (PAMA), and a polymethylmethacrylate. Transcutol (TR), mint essential oil, Lauroglycol, Brij 58, and propylene glycol (PG) were evaluated as DHEA skin permeation enhancers. All prepared patches were characterized by drug content, light microscopy, and in vitro skin permeation, performed using a modified Franz-type diffusion cell and human stratum corneum and epidermis as a membrane. The in vitro skin permeation studies are particularly significant in the development studies of DHEA patches as the in vivo determination of DHEA is affected b the fact that the endogen substance in the plasma is not constant over time. Among the testedpatches, highest DHEA fluxes were obtained using the formulation based on PAMA. Moreover, the introduction in the matrix of binary mixtures of TR and PG, used also for their plasticizer properties, permitted enhancing DHEA skin permeation. On the basis of these studies, the transdermal administration of DHEA using patches seems feasible.

Administration, Cutaneous↗
PubMed2000

Impact of delirium on the short term prognosis of advanced cancer patients. Italian Multicenter Study Group on Palliative Care.

BACKGROUND: The objective of this study was to evaluate the impact of delirium on the survival of advanced cancer patients also assessed with a validated prognostic score (the palliative prognostic [PaP] score). METHODS: The study population was a prospective multicenter consecutive case series of advanced cancer patients for whom chemotherapy was no longer considered viable and who were referred to palliative care programs. Clinical and biologic prognostic factors included in the PaP score were assessed at study entry. The Confusion Assessment Method criteria were applied to screen patients presenting with delirium. Survival times were measured from time of enrollment and death taken as an outcome. Survival curves were traced with the Kaplan-Meier method and comparison were based on log rank tests. RESULTS: Delirium was found in 109 cases among 393 consecutive patients (27.7%). The diagnosis of delirium was independently associated with male gender, central nervous system metastases, lower performance status, worse clinical prediction of survival, and progestational treatment. The survival curve of patients with delirium was significantly different from the nondelirious patients curve (log rank, 31.6, P < 0.0001). The median survival time was 21 days (95% confidence interval [CI], 16-27) for the delirious patients and 39 days (95% CI 33-49) for the others. Multivariate analysis showed that the diagnosis of delirium and PaP score were independently associated with prognosis. CONCLUSIONS: The diagnosis of delirium significantly worsens life expectancy prognosticated with the PaP score. By using the PaP score together with the assessment of cognitive status, physicians can correctly predict patients 30-day survival in greater than 70% of cases.

Adolescent↗
PubMed2000

The situation of OTC drugs in italy compared to the other EU states.

Even if a specific directive has been approved many years ago, the situation of self-medication products (OTC) in EU countries is still far from being harmonized. In Italy the market is lower than that of most other countries; in order to solve some of the major problems that led to this situation a guideline, concerning the criteria for the definition of an OTC product, and the characteristics of the label and the package leaflet, was recently published. In this document the characteristics of OTC, such as composition, indications and duration of the treatment are assessed. The European Commission has recently published a guideline on the readability of labels and package leaflets of medicinal products for human use. The two documents stated the same principles and the Italian document is in agreement with the European guidelines. In this paper the Italian situation of OTC products (definition and presentation) is presented and discussed.

Drug Labeling↗
PubMed2000

A proposal to improve the supply of orphan drugs.

Industrial medicinal products are not always available for the treatment of some specific patients or diseases. Appropriate research on orphan drugs, neglected doses or administration routes and patients' sensitivity to excipients, as an example, might lead to interesting results in this respect. In the United States, a specific legislation on orphan drugs dates back to 1983; in the European Union, regulations are currently being studied. The industrial production of orphan drugs might be improved following the adoption of adequate incentives. New regulations should also take care of neglected doses, and stimulate the preparation of galenic products, as an example by including a number of monographs on orphan drugs in Pharmacopoeias and National Formularies. As a matter of fact, magistral and officinal preparations made in community and hospital pharmacies in accordance with a medical prescription or with the prescription of a Pharmacopoeia or an Official Formulary, can represent an effective alternative. In this paper, the regulations enforced in the USA and Japan, the European situation, possible incentives to the industry and the role of galenic products will be discussed.

Drug and Narcotic Control↗
PubMed2000

Solvation enthalpies as descriptors of structure--in vitro percutaneous permeation relationship of benzoxazinones regioisomers.

The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient (Kp), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH3, OH, OCH3, and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The Kp values were in the range 0.14-8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P, molecular weight and volume (MV), hydrogen bond donor (Hd) and acceptor activity (Ha), and molecular refractivity were considered, with the addition of solvation enthalpy (delta deltaHsolv). Delta deltaHsolv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between Kp and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with delta deltaHsolv had a good correlation (r2 = 0.749, F = 16.43, P = 0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, Hd and Ha (r2 = 0.830, F = 16.3, P = 0.0004).

Humans↗
PubMed2000

Development of local patches containing melilot extract and ex vivo-in vivo evaluation of skin permeation.

Melilot extract could be effective in treating localised varicose syndrome or capillary fragility. The monolayer patch was selected to obtain a prolonged release of coumarin contained in the phytocomplex. Two types of methacrylic patches (patch 1 based on a blend of Eudragit E100 and Eudragit NE; patch 2 based on Eudragit L100) were prepared. Both patches were equivalent in terms of coumarin release and ex vivo skin permeation profiles. The two patches differed significantly as regards respective adhesive properties. At low peel rate only patch 1 showed adhesive failure as confirmed by the in vivo performance. When comparing the behaviour of the patches containing melilot extract with analogous patches containing synthetic coumarin, no melilot phytocomplex enhancer effect was shown. The data of the ex vivo coumarin skin permeation and those obtained by the in vivo stripping technique showed a good correlation (r(2)=0.9727 for patch 1, r(2)=0.9835 for patch 2).

Adhesiveness↗
PubMed2000

Beer increases plasma antioxidant capacity in humans.

The positive association of a moderate intake of alcoholic beverages with a low risk for cardiovascular disease, in addition to ethanol itself, may be linked to their polyphenol content. This article describes the effect of acute ingestion of beer, dealcoholized beer, and ethanol (4.5% v/v) on the total plasma antioxidant status of subjects, and the change in the high performance liquid chromatography profile of some selected phenolic acids (caffeic, sinapic, syringic, and vanillic acids) in 14 healthy humans. Plasma was collected at various times: before (T0), 1 hour after (T1), and 2 hours after (T2) drinking. The study is part of a larger research planned to identify both the impact of brewing on minor components potentially present in beer and their metabolic fate in humans. Beer was able to induce a significant (P < 0.05) increase in plasma antioxidant capacity at T1 (mean +/- SD: T0 1,353 +/- 320 microM; T1 1,578 +/- 282 microM), returning close to basal values at T2. All phenolic acids measured in plasma tended to increase after beer intake (20% at T1, 40% at T2). Syringic and sinapic acid reached statistical significance (P < 0.05 by one-way analysis of variance-Fisher's test) at T1 and T2, respectively. Plasma metabolic parameters (glucose, total cholesterol, triglycerides, and uric acid) and plasma antioxidants (alpha-tocopherol and glutathione) remained unchanged. Ethanol removal impaired the absorption of phenolic acids, which did not change over the time of the experiment, accounting for the low (and not statistically significant) increase in plasma antioxidant capacity after dealcoholized beer drinking. Ethanol alone did not affect plasma antioxidant capacity or any of the antioxidant and metabolic parameters measured.

Journal Article↗
PubMed2000

Porous ceramic bodies for drug delivery.

An approach to the production of ceramic drug delivery devices is proposed. Two examples of possible ceramics are dealt with: hydroxyapatite weakly modifiable by living tissue and the bioinert alumina. The possibility to control the formed porosity was taken into consideration for both materials. The ratio between the acquired porosity and the quantity and quality of the agents inducing porosity is also described and discussed. A test on the role of porosity was performed on the obtained porous ceramic bodies and a study was made on the release of a substance with pharmacological activity from previously impregnated porous ceramic bodies. This paper is preliminary to a planned work targeted to the preparation of ceramic drug delivery systems.

Journal Article↗
PubMed2000

Acitretin and treatment of the oral leucoplakias. A model to have an active molecules release.

AIMS: The aim of this study was to investigate the effectiveness of acitretin in a new topical formulation (mucoadhesive two-layer tablets) for the treatment of oral leucoplakias. METHODS: Twenty-one volunteers, 16 men, five women, with oral leucoplakia (histologically diagnosed), were included in this double-blind placebo-controlled study. Patients were randomized in three groups (A, B, C) of seven patients each. Groups A and B received tablets with different in vitro release profiles, and group C subjects (controls) received tablets without acitretin. The acitretin dose was 20 mg/day (two 10 mg tablets daily). Serum aspartate aminotransferase, alanine aminotransferase, cholesterol and triglycerides were evaluated before and after treatment. At the end of therapy the concentrations of acitretin in plasma, saliva and tissue were measured by high-performance liquid chromatography. RESULTS: At the end of the study 71% (groups A and B) of patients showed clinical remission or marked improvement. No improvement was noted in the control subjects (group C). These results were further confirmed by histological findings. There were no significant changes in laboratory values in the three groups. The acitretin concentration in plasma and tissue ranged from 0 to 50 mg with no difference between groups A and B, and it was very high in saliva (ranging from 4.9 to 43 mg) with higher concentrations in group A than in group B (due to a longer adhesion time in group A). Patients' compliance was excellent. The results show that mucoadhesive tablets of topical acitretin are efficacious in the treatment of oral leucoplakia without systemic side-effects.

Acitretin↗
PubMed1999

Application of viscometry and solubility parameters in miconazole patches development.

Nine binary mixtures of seven different methacrylic copolymer systems (Plastoid((R)) E 35 L (PLE) and Plastoid((R)) L 50 (PLL); Eudragit((R)) (Eu) NE, RL, RS, L, S) were tested as components of monolayer patches containing miconazole. Only three mixtures (PLE:EuNE, PLE:EuRL and PLE:EuRS) were suitable for the preparation of placebo matrices. Miconazole patches with good technological characteristics were obtained by using mixtures of PLE:EuNE and PLE:EuRL. The in vitro miconazole release rate from the two patches and from the patch prepared using only PLE were significantly different. The amounts of drug released in 24 h were quite satisfactory. A mathematical model based on capillary viscometry data was used for the evaluation of interactions between copolymers. This was useful to predict and understand the mechanisms related to the instability of the prepared mixture. The solubility parameters of the drug and of the matrix were also calculated. Miconazole release was faster when the difference between the solubility parameters of the matrix and of the drug was higher. A relationship between miconazole release rate and the difference of drug and matrix solubility parameters was found. Therefore, the solubility parameter could be applied in formulation studies of patches.

Adhesiveness↗
PubMed1999

Fetal erythroblast isolation up to purity from cord blood and their culture in vitro.

BACKGROUND: Erythroblasts have been the most encouraging candidate cell type for noninvasive prenatal genetic investigation. We previously showed that human erythroblasts can be recovered from bone marrow and blood bank buffy coats by a physical cell separation. In the present study, we modified our previous methodology, taking into account the peculiar behavior of erythroblasts in response to modifications of pH and osmolality of the separation medium. METHODS: Twenty to forty milliters of cord blood were initially centrifuged on Ficoll/diatrizoate (1.085 g/ml). The interphase cells were further separated on a continuous density gradient (1.040-1.085 g/ml). Two different gradients were initially compared: the first was iso-osmolar and neutral, whereas the second also contained an ionic strength gradient and a pH gradient (triple gradient). A subsequent monocyte depletion was performed by using magnetic microbeads coated with anti-CD14 monoclonal antibody (mAb), and erythroblasts were purified by sedimentation velocity. Purified cells were investigated by analyses with fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization (FISH) and immunocytochemistry with mAb against fetal hemoglobin and were cultured in vitro. RESULTS: When nucleated cells were spun on an iso-osmolar and neutral continuous density gradient, two separated bands of nucleated red blood cells (NRBCs) were obtained: a light fraction banding at 1.062 g/ml and an heavy fraction banding at 1.078 g/ml. Conversely, when cells were spun in the triple gradient, NRBCs were shifted to the low-density region. Monocyte depletion by immunomagnetic microbeads and velocity sedimentation provided a pure erythroblast population. FACS and FISH analyses and immunocytochemistry substantiated the purity of the isolated cell fraction, which was successfully cultured in vitro. CONCLUSIONS: We have shown that fetal erythroblasts can be purified up to homogeneity from cord blood, but further refinements of the isolation procedure are necessary before the same results can be obtained from maternal peripheral blood.

Blood Sedimentation↗