Eleonora Russo

Development and Characterization of a Buccoadhesive Dosage Form of Oxycodone Hydrochloride

AbstractA buccoadhesive system for the delivery of oxycodone hydrochloride to the oral mucosa was prepared from a colloidal solution of gelatin used as a bioadhesive agent. An in vitro method for measuring the adhesion of release system to a substrate was developed by employing a modified balance. The eflects of thickness and of the presence of the drug on swelling and mucoadhesion properties were evaluated. The in vitro release of the buccoadhesive formulation was studied by a USP paddle dissolution apparatus and the results were fitted to an empirical equation. In vivo compliance and permanence time in 10 healthy volunteers were estimated.

Development and In Vitro Evaluation of Buccoadhesive Tablets Using a New Model Substrate for Bioadhesion Measures: The Eggshell Membrane

For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders. Metronidazole and benzydamine were used as model drugs. The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane). The use of the biological substrate seemed to supply more reliable data. All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems.

Antimicrobial Activity of the Ornamental Species Salvia corrugata, a Potential New Crop for Extractive Purposes

As a part of our search for biologically active compounds from cultivated Salvia spp. we investigated Salvia corrugata Vahl. The activity of two isolated icetaxane diterpene quinones, fruticuline A and demethylfruticuline A, was assessed against 46 bacterial pathogens, mostly resistant to several primary antibiotics. The MIC for all the inhibited Gram-positive pathogens tested showed a very narrow distribution and ranged from 32 to 64 mg/L, regardless of their resistance patterns to other antibiotics. Demethylfruticuline A was shown to be highly bactericidal (>3 log(10) CFU decrease within 24 h) against Staphylococcus aureus and S. epidermidis and bacteriostatic against Enterococcus faecalis and E. faecium. Fruticuline A manifested bacteriostatic activity against all tested strains. S. corrugata can be viewed as an interesting source for these diterpenes, which, if well tolerated in vivo, may represent new medical agents useful for the treatment of serious infections caused by resistant Gram-positive pathogens.

Buccoadhesive oxycodone hydrochloride disks: plasma pharmacokinetics in healthy volunteers and clinical study

Abstract The pharmacokinetics of oxycodone hydrochloride were investigated following a single 10 mg buccal dose administered to nine healthy volunteers. Plasma samples were collected up to 24 h after administration and analyzed by an original, sensitive and specific selected ion monitoring (SIM) gas chromatography/mass spectrometry (GC-MS) assay, after purification with a solid-phase extraction procedure. The limit of quantitation was 1 ng/ml using a 1 ml plasma sample. The AUC 0–∞ and the C max data of oxycodone hydrochloride were similar to the values reported in the literature for conventional oral tablets. The t max data obtained seem greater for the buccoadhesive disks compared with other oral dosage forms. Mucoadhesion, mucosal irritation and comfort were assessed. No serious problems were encountered. The administration of the new dosage form to cancer patients produced effective pain control, allowing a reduction in the dosing frequency.

An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose

An innovative matrix, produced by thermal treatment on direct compression (DC) tablets containing polycarbophil (POL) and ethylcellulose (EC), identified as matrix forming polymers, and able to control the release of diltiazem hydrochloride, was developed. At pH 7.2, 72 ± 1.2% (w/w) of drug loaded was released in 25 h, mostly at constant rate. This swellable and unerodible matrix controls drug release by an anomalous transport mechanism. The modifications induced by the thermal treatment are irreversible and can be used to control and characterize the matrix. A 3-component constrained mixture design allowed the investigation of the experimental domain in which the matrix forms and the computation of a mathematical model that can be used to optimize the formulation properties. The release rate can be modulated (0.032-0.064% drug released/min) through the choice of suitable treatment conditions and tablet composition. The maximum amount of diltiazem hydrochloride released by zero-order kinetics, at the lowest release rate, occurs for POL:EC ratio in the range of 1:1-2:3 with 20-30% of diluent. The tablets are able to load up to 50% (w/w) of diltiazem hydrochloride without losing their properties. A stability study performed on a selected formulation containing DTZ showed stability for at least 2.7 years at RT conditions.

A chitosan lactate/poloxamer 407-based matrix containing Eudragit RS microparticles for vaginal delivery of econazole: design and in vitro evaluation.

A matrix based on chitosan lactate and poloxamer 407 was evaluated as a delivery system for the vaginal administration of the antifungal drug econazole. The matrix was investigated both containing the pure drug and after introducing microparticles of Eudragit RS 100 containing econazole. Eudragit RS 100 microparticles were prepared using an emulsion-extraction method and dispersed in a solution containing chitosan lactate (2% w/w) and poloxamer 407 (1.7% w/w). The microparticles, obtained with a yield of 64% w/w and an encapsulation efficiency of 42% w/w, had a diameter of less than 2 μm and a drug loading of 13% w/w. The compressed matrices, characterized by DSC, swelling, erosion, release and mucoadhesion studies, had behaviours dependent on the relative amounts of the contained microparticles. The matrix without microparticles (MECN) showed zero-order release kinetics, with a maximum drug-release of 60% w/w, while those containing 50 or 75% w/w microparticles showed a diffusion controlled release up to 8 and 16 h, respectively, and a linear trend after those time intervals, caused by the erosion process, which allowed reaching a drug-release of approximately 100% w/w at 22 h. In in vitro experiments, the matrices were mucoadhesive and active in inhibiting the growth of Candida albicans 796.

Development, characterization and preliminary clinical evaluation of mucoadhesive vaginal gels containing chlorhexidine digluconate

Gels containing chlorhexidine, based on hydroxyethylcellulose or its mixtures with either hydroxypropylmethylcellulose or chitosan, were prepared and characterized by in vitro drug release, swelling, mucoadhesion and rheological studies. All formulations provided a controlled drug delivery showing in general a decrease in drug release rate with the increase of the total polymer concentration. Formulations containing either hydroxyethylcellulose or its mixtures with hydroxypropylmethylcellulose presented similar strength of gel network that was markedly higher compared to gels based on mixtures with chitosan at the same total polymer concentration. Drug release was more sustained when gel components were mixtures of hydroxyethylcellulose and hydroxypropylmethylcellulose. Mucoadhesion was similar for all preparations. Viscosity measurements gave higher values in correspondence to higher total polymer concentrations. A candidate vaginal gel formulation containing hydroxyethylcellulose at 2.5% (w/w) induced a clinical remission in 93% of patients affected by bacterial vaginosis compared to 76% of patients belonging to a metronidazole treatment group, and in 84% of subjects with Candida infections compared to 83% receiving clotrimazole. No adverse events were reported during the trial in any patient. Patient compliance with the mucoadhesive gel was good.

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy

Abstract Objective: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone. Materials and methods: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application. Results and discussion: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8 min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation. Conclusions: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.