V. De Caro

A new delivery system of clobetasol‐17‐propionate (lipid‐loaded microspheres 0·025%) compared with a conventional formulation (lipophilic ointment in a hydrophilic phase 0·025%) in topical treatment of atrophic/erosive oral lichen planus. A Phase IV, randomized, observer‐blinded, parallel group clinical trial

Background  Topical application of clobetasol‐17‐propionate has been diffusely reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP), without exposing the patient to systemic side‐effects. However, prolonged contact and respective topical effects on the oral mucosa should be avoided.

Response characterization of ammonium tartrate solid state pellets for ESR dosimetry with radiotherapeutic photon and electron beams

Solid state pellets (1 mm thick) for electron spin resonance (ESR) dosimetry were made using ammonium tartrate as the radiation-sensitive substance. Their behaviour was experimentally investigated as a function of dose with 60Co gamma rays. The calibration function obtained permits measurements of absorbed dose in the 2-50 Gy range, with a combined uncertainty of +/-4%. The lowest detectable dose was about 0.5 Gy. These properties are comparable with or even better than those of ESR dosimeters made from other materials. The time stability of the ESR signal of ammonium tartrate dosimeters at different storage conditions after irradiation was studied. A rather complex behaviour was observed, which suggests that more species of free radicals are produced by radiation and that migration processes may be effective. No dependence of the response on beam quality was found for high-energy photon and electron beams produced by a linear accelerator used in radiotherapy, whereas dose was underestimated with low-energy x-rays.

Carnauba wax microspheres loaded with valproic acid : preparation and evaluation of drug release

AbstractTo minimize unwanted toxic effects of valproic acid (1) by the kinetic control of drug release, gastroresistant carnauba wax microspheres loaded with the antiepileptic agent were prepared. The preparation was based on a technique involving melting and dispersion of drug-containing wax in an aqueous medium. The resulting emulsion after cooling under rapid stirring produced solid, discrete, reproducible free flowing microspheres which converted the liquid drug droplets into solid material. About 94% of the isolated microspheres were of particle size range 200-425 μm. The microspheres were analyzed to determine the drug content in various particle size range and to characterize the in vitro release profile. The average drug content was 26% w/w. The intestinal drug discharge of 1 from the carnauba wax microspheres was studied and compared with the release patterns observed for white beeswax and hexadecanol microspheres previously described. The drug release performance was greatly affected by the mate...

New prospective in treatment of Parkinson's disease: Studies on permeation of ropinirole through buccal mucosa

The aptitude of ropinirole to permeate the buccal tissue was tested using porcine mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation was also evaluated in presence of various penetration enhancers and in iontophoretic conditions. Ropinirole, widely used in treatment of motor fluctuations of Parkinsons disease, passes the buccal mucosa. Flux and permeability coefficient values suggested that the membrane does not appear a limiting step to the drug absorption. Nevertheless, an initial lag time is observed but the input rate can be modulated by permeation enhancement using limonene or by application of electric fields. Absorption improvement was accompanied by the important reduction of the lag time; at once the time required to reach the steady state plasma concentration was drastically decreased. On the basis of these results we could assume that clinical application of ropinirole by buccal delivery is feasible.

New Prospectives in the Delivery of Galantamine for Elderly Patients Using the IntelliDrug Intraoral Device: In Vivo Animal Studies

The transbuccal delivery of drugs could assist several categories of chronic, especially elderly, patients in adhering to a correct dosage regimen. In particular, patients suffering from dementia have several difficulties in following the prescribed dosage, in addition to problems associated with swallowing tablets. Galantamine is currently used for treating patients with mild to moderate Alzheimers-type dementia. The transbuccal delivery of this drug could be an interesting non- invasive and safe administration route. Several studies have been performed in vitro and ex vivo within the framework of a European Commission funded Project (IntelliDrug-FP6), aimed at developing a device which would be fitted for controlled delivery of drugs by an electronic and software-driven system. The primary objective of this study was to evaluate the efficacy of a prototype of the IntelliDrug device in vivo on 6 pigs, following a single Galantamine dose to be delivered through the buccal mucosae, as compared to intravenous drug injection. The secondary objectives were: a) to verify Galantamine bioavailability through buccal delivery; b) to evaluate the permeation enhancement effect of iontophoresis; and, finally, c) to assess any histomorphological changes in the buccal mucosae after transbuccal delivery. The results suggested that transbuccal delivery has the potential to cause long-lasting and controlled blood levels of Galantamine. The latter crosses the entire buccal mucosae, reaching systemic circulation after about 30 minutes and its plasmatic peak approximately 120 minutes after administration. The histological analysis of the buccal mucosae did not reveal any evidence of flogosis or tissue injury. Our results have clearly confirmed that the buccal delivery of Galantamine is a reliable tool with which to overcome the drawbacks associated with the conventional administration route. In general, transbuccal drug delivery has been shown to be an interesting, non-invasive and safe administration route for delivering systemically-acting drugs.

Preparation of white beeswax microspheres loaded with valproic acid and kinetic study of drug release

AbstractThe well known antiepileptic valproic acid (1) due to the long treatment of epilepsy may induce many adverse side effects on various systems. To minimize unwanted toxic effects by kinetic control of drug release, 1 was physically entrapped into white beeswax microspheres using the meltable dispersion process utilizing wetting agents. Solid, discrete, reproducible free flowing microspheres were obtained converting the liquid drug droplets into solid material. The average drug content was 17% w/w. More than 95% of the isolated microspheres were of particle size range 200-425 µm. The microspheres were analyzed to quantify the amount of incorporated drug and to characterize the in vitro release profile. The matematical approach to drug release using standard equations indicated that the first order equationis was the most appropriate one for describing the initial drug release profile; after about the 507–60% of drug was discharged numerical data fit well with the root of time equation. The drug remov...

Entrapment of Phenytoin into Microspheres of Oleaginous Materials: Process Development and in Vitro Evaluation of Drug Release

AbstractA novel multiparticulate preparation of the antiepileptic agent phenytoin (1) was developed and evaluated in vitro. The preparation consists of gastroresistant microparticulate drug delivery system formulated with oleaginous material (lipospheres) to minimize unwanted effects of l on gastric apparatus. The drug was dispersed in a spherical micromatrix consisting of a mixture of stearyl alcohol and glycerol esters of various fatty acids. The best mixture to obtain discrete, reproducible, free-flowing lipospheres consisted of glyceryl monostearate dilaurate and stearyl alcohol (ratio 3: 17). The lipospheres were obtained by a technique involving melting and dispersion of drug-containing oleaginous material in aqueous medium. The oily droplets of the resulting emulsion after cooling under rapid stirring were transformed into solid. About 99% of the lipospheres were of particle size range 100–800 pm. The lipospheres were analyzed to determine the drug content in various particle sizes and to character...

Comparative in vitro evaluation of cumulative release of the urinary antiseptics nalidixic acid, pipemidic acid, cinoxacin, and norfloxacin from white beeswax microspheres

AbstractThe in vitro diffusion of nalidixic acid (1), pipemidic acid (2), cinoxacin (3), and norfloxacin (4) was studied. The transfer rate constants (kd) from simulated gastro-intestinal juices to simulated plasma, throughout artificial wall lipid membranes, were defined. The kd values suggested that the four drugs are absorbed both in gastric and intestinal environments in similar amounts. To obtain lack of gastric unwanted effects white beeswax microspheres containing 1, 2, 3, and 4 were investigated as a vehicle for the drug intestinal release; they were prepared by the meltable dispersion process using wetting agents. Discrete, reproducible free flowing microspheres were obtained. The drug content increased when the particle size growed; it ranged from 4% to 18%. More than 95% of the isolated microspheres were of particle size range 100–500 μm. The drug release was evaluated in vitro. Dissolution of entrapped active ingredients was greatly retarded allowing absorption only in the intestinal tract as ...

Physical Methods for Enhancing Oral Mucosal Delivery: Sonophoresis, Iontophoresis and Electroporation

The need for more rapid onset of action and improved absorption of medications has resulted in great development of drug delivery technologies.

ESR Evaluation of stable free radicals produced by ionizing radiation in multifunctional substances. Application for absorbed dose measurements in radiotherapy

Electron Spin Resonance dosimetry is a useful system for measuring absorbed dose in radiotherapy. This work describes the results obtained at the University of Palermo regarding an experimental study aimed to optimize the properties of alanine based dosimeters and to analyze other materials, that could be alternatives to alanine.