Development of Oral Tablets of Nebivolol with Improved Dissolution Properties, Based on Its Combinations with Cyclodextrins.

New oral tablets of nebivolol have been developed aiming to improve, by cyclodextrin (CD) complexation, its low solubility/dissolution properties-the main reason behind its poor/variable oral bioavailability. Phase-solubility studies, performed using βCD and highly-soluble βCD-derivatives, indicated sulfobutylether-βCD (SBEβCD) as the best solubilizing/complexing agent. Solid drug-SBEβCD systems were prepared by different methods and characterized for solid-state and dissolution properties.

Technical Evaluation of a New Medical Device Based on Rigenase in the Treatment of Chronic Skin Lesions.

Chronic wound is characterized by slow healing time, persistence, and abnormal healing progress. Therefore, serious complications can lead at worst to the tissue removal. In this scenario, there is an urgent need for an ideal dressing capable of high absorbency, moisture retention and antimicrobial properties.

Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use.

There is a serious need of pediatric drug formulations, whose lack causes the frequent use of extemporaneous preparations obtained from adult dosage forms, with consequent safety and quality risks. Oral solutions are the best choice for pediatric patients, due to administration ease and dosage-adaptability, but their development is challenging, particularly for poorly soluble drugs. In this work, chitosan nanoparticles (CSNPs) and nanostructured lipid carriers (NLCs) were developed and evaluated as potential nanocarriers for preparing oral pediatric solutions of cefixime (poorly soluble model drug).

Researching the level of agreement among experts on terms used to describe wounds: An international study.

Establishing a common language that allows univocal and objective communication in describing wounds and their healing is of utmost importance in defining the diagnostic hypothesis and proper wound management. To measure the level of agreement on the description of wounds, an international study was performed among experts of different professional backgrounds on several common terms used to describe ulcerative lesions. A panel of 27 wound care experts anonymously completed a multiple-choice questionnaire on 100 images of 50 ulcerative lesions.

Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System.

Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels' loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based nanogels requires the use of specially modified CDs, or of crosslinking agents.

Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review.

Chitosan (CS) is a linear polysaccharide obtained by the deacetylation of chitin, which, after cellulose, is the second biopolymer most abundant in nature, being the primary component of the exoskeleton of crustaceans and insects. Since joining the pharmaceutical field, in the early 1990s, CS attracted great interest, which has constantly increased over the years, due to its several beneficial and favorable features, including large availability, biocompatibility, biodegradability, non-toxicity, simplicity of chemical modifications, mucoadhesion and permeation enhancer power, joined to its capability of forming films, hydrogels and micro- and nanoparticles. Moreover, its cationic character, which renders it unique among biodegradable polymers, is responsible for the ability of CS to strongly interact with different types of molecules and for its intrinsic antimicrobial, anti-inflammatory and hemostatic activities.

4-Heteroaryl Substituted Amino-3,5-Dicyanopyridines as New Adenosine Receptor Ligands: Novel Insights on Structure-Activity Relationships and Perspectives.

A new set of amino-3,5-dicyanopyridines was synthesized and biologically evaluated at the adenosine receptors (ARs). This chemical class is particularly versatile, as small structural modifications can influence not only affinity and selectivity, but also the pharmacological profile. Thus, in order to deepen the structure-activity relationships (SARs) of this series, different substituents were evaluated at the diverse positions on the dicyanopyridine scaffold.

Combined Use of Cyclodextrins and Amino Acids for the Development of Cefixime Oral Solutions for Pediatric Use.

Cefixime (CEF) is a cephalosporin included in the WHO Model List of Essential Medicines for Children. Liquid formulations are considered the best choice for pediatric use, due to their great ease of administration and dose-adaptability. Owing to its very low aqueous solubility and poor stability, CEF is only available as a powder for oral suspensions, which can lead to reduced compliance by children, due to its unpleasant texture and taste, and possible non-homogeneous dosage.

Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery.

A thermosensitive, mucoadhesive in-situ gel for clonazepam (CLZ) intranasal delivery was developed, which aimed to achieve prolonged in-situ residence and controlled drug release, overcoming problems associated with its oral or parenteral administration. Poloxamer was selected as a thermosensitive polymer and chitosan glutamate and sodium hyaluronate as mucoadhesive and permeation enhancer. Moreover, randomly methylated β-Cyclodextrin (RAMEB) was used to improve the low drug solubility.

Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex.

This work was aimed at enhancing butamben (BTB) anesthetic efficacy by the "drug-in cyclodextrin (CD)-in deformable liposomes" strategy. In the study, phase-solubility studies with natural (α-, β-, γ-) and derivative (hydroxypropyl-α-and β-, sulfobutylether-β, methyl-β) CDs evidenced the highest BTB affinity for βCD and its derivatives and indicated methyl-βCD (RAMEB) as the best carrier. Drug-RAMEB complexes were prepared by different techniques and were characterized for solid-state and dissolution properties.

Development of a stable oral pediatric solution of hydrochlorothiazide by the combined use of cyclodextrins and hydrophilic polymers.

Hydrochlorothiazide (HCT) is widely used in pediatrics for hypertension management. Due to the lack of pediatric commercial forms, community or hospital pharmacies generally prepare HCT extemporaneous pediatric suspensions by dispersing in water a portion of a crushed tablet or the drug powder; however, any dose or stability control is usually done on these preparations. Obtaining stable HCT solutions is very challenging, due to its low water-solubility and pH-dependent degradation.

Characterization and evaluation of the performance of different calcium and magnesium salts as excipients for direct compression.

The performance of a series of inorganic salts as direct compression excipients was systematically evaluated. The physical-chemical and technological properties of the different salts were investigated in terms of crystalline/amorphous state, morphology, granulometry, apparent/tapped density, specific surface area, flowability, compressibility, dilution and distribution coefficients. To achieve a comprehensive evaluation of the performance of the different salts, the data obtained by the various analyses were normalized, giving a score to each excipient for each evaluated property/parameter.

Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy.

The hydrochlorothiazide (HCT) low solubility and permeability give rise to limited and variable bioavailability; its low stability makes it difficult to develop stable aqueous liquid formulations; its low dose makes the achievement of a homogeneous drug distribution very difficult. Thus, the aim of this study was to investigate the effectiveness of a strategy based on the development of nanostructured lipid carriers (NLC) as an innovative oral pediatric formulation of HCT with improved therapeutic efficacy. The performance of various synthetic and natural liquid lipids was examined and two different preparation methods were employed, i.

A preliminary study for the development and optimization by experimental design of an in vitro method for prediction of drug buccal absorption.

The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation of drug absorption through buccal mucosa. Absorption simulator apparatus endowed with an artificial membrane was purposely developed by experimental design. The apparent permeation coefficient (P) through excised porcine buccal mucosa of naproxen, selected as model drug, was the target value to obtain with the artificial membrane.

In situ mucoadhesive-thermosensitive liposomal gel as a novel vehicle for nasal extended delivery of opiorphin.

Previous studies proved the effectiveness of an intravenous PEGylated liposomal formulation of opiorphin (1mg/mL) in protecting the drug from enzymatic degradation, and improving intensity and duration of its painkilling effect. Therefore, considering the advantages of nasal administration, the aim of this work was the development of a liposomal mucoadhesive thermo-sensitive in situ gel for the extended nasal delivery of opiorphin. With this purpose, the potential of a series of combinations of different polymers (i.

Development and Optimization by Quality by Design Strategies of Frovatriptan Orally Disintegrating Tablets for Migraine Management.

Background: Frovatriptan is a potent anti-migraine agent with unfavourable slow onset of action, available on the market as film-coated tablets.

Objective: Optimization, by Quality by Designs strategies, of an orally disintegrating tablet (ODT) formulation of frovatriptan aimed to make its oral administration easier and its dissolution faster than the commercial tablets, thus improving its effectiveness in migraine management.

Method: A screening D-optimal design was applied to investigate the effects of different levels of kind and amount of ODT special excipient and disintegrant agents (identified as the critical variables) on disintegration time (DT) and % drug dissolved at 30 s (%Diss), selected as the responses to optimize.

Development and characterization of fast dissolving tablets of oxaprozin based on hybrid systems of the drug with cyclodextrins and nanoclays.

Previous studies highlighted an increase of the randomly-methylated-ß-cyclodextrin (RAMEB) solubilizing power towards oxaprozin when used in combination with L-arginine (ARG) or sepiolite nanoclay (SV). Therefore, the aim of this work was to investigate the possibility of maximising the RAMEB solubilizing efficacy by a joined approach based on the entrapment in SV of the drug-RAMEB-ARG complex. The quaternary nanocomposite was prepared by different techniques and characterized for solid state and dissolution properties, compared to ternary drug combinations with RAMEB-ARG, RAMEB-SV or ARG-SV.

Development and in vivo evaluation of an innovative "Hydrochlorothiazide-in Cyclodextrins-in Solid Lipid Nanoparticles" formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics.

An innovative pediatric oral formulation of hydrochlorothiazide (HCT) (2mg/mL), endowed with improved bioavailability and sustained release properties and suitable for the hypertension treatment in pediatric patients, was developed by combining the drug-cyclodextrin complexation and the incorporation of the complex into Solid Lipid Nanoparticles (SLN). PrecirolATO5-based SLN, with two different surfactants (PluronicF68 and Tween80) loaded with the drug as such or as binary system with hydroxypropyl-beta-cyclodextrin (HPβCd) and sulfobutyl-ether-beta-cyclodextrin (SBEβCd) both as physical mixture (P.M.

Injectable liposomal formulations of opiorphin as a new therapeutic strategy in pain management.

Background: Conventional and PEGylated liposomes were developed, aimed at improving the pain-killing effect of opiorphin.

Methods: The antinociceptive action of the formulations was investigated on rats (tail-flick test), and compared with that of opiorphin and morphine aqueous solutions (all at 5 mg/kg).

Results: Opiorphin loading in conventional liposomes enabled a 28% AUC increase with respect to free peptide.

Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy.

Development of cyclodextrin hydrogels for vaginal delivery of dehydroepiandrosterone.

Objective: To develop a new vaginal delivery system for a sustained release of dehydroepiandrosterone (DHEA) in the treatment of postmenopausal symptoms, aimed to overcome the problems of poor bioavailability of the drug related to its very low water solubility.

Methods: Cyclodextrin (CD)-containing hydrogels were developed, combining in a single device the hydrogel controlled release and mucoadhesion properties, and the CD solubilizing power towards DHEA. The effect of different CDs, alone or in mixtures, on the hydrogel technological and mucoadhesion characteristics was investigated.

Amidated pectin-based wafers for econazole buccal delivery: formulation optimization and antimicrobial efficacy estimation.

Combinations of low-methoxy amidated pectin (LMAP) and carboxymethylcellulose (CMC) were used to develop a lyophilized wafer formulation, aimed to obtain prolonged residence and controlled release of econazole nitrate (ECN) in the oral cavity. Ternary ECN/sulphobutylether-ß-cyclodextrin/citric acid complex, resulted as the most efficient system against selected Candida strains, was loaded into this formulation. The final product with the desired and predicted quality was developed by an experimental design strategy.

Development of liposomal and microemulsion formulations for transdermal delivery of clonazepam: effect of randomly methylated β-cyclodextrin.

Transdermal administration of clonazepam, a poorly water-soluble benzodiazepine, is an interesting strategy for overcoming the drawbacks of its oral administration. With this aim, two nano-carrier formulations, based on ultra-deformable liposomes and microemulsions, have been developed to favour clonazepam transdermal delivery. Considering the solubilizing power of methyl-βcyclodextrin (Me-βCD) toward clonazepam and its potential positive influence on transdermal drug delivery, the effect of its addition to these formulations was investigated.

Comparative analysis of binary and ternary cyclodextrin complexes with econazole nitrate in solution and in solid state.

The aim of this work was to investigate in-depth interactions of econazole nitrate (ECN), a very poorly water-soluble antifungal agent, with different β-cyclodextrin (βCD) derivatives, and to evaluate the potential synergistic effect of suitable third compounds (l-amino acids, citric acid, hydrophilic polymers). Phase-solubility studies showed the formation of equimolar complexes with all tested CDs, and indicated sulfobutyl-βCD (SBEβCD) as the best complexing and solubilizing agent for ECN, followed by hydroxypropyl-βCD (HPβCD). 1D and 2D (1)H NMR studies demonstrated the actual formation of inclusion complexes of 1:1mol:mol stoichiometry, and gave insight about different inclusion modes of ECN molecule into the CD cavity, simultaneously existing in solution.

Physico-chemical characterization in solution and in the solid state of clonazepam complexes with native and chemically-modified cyclodextrins.

Clonazepam (CLZ) is a benzodiazepine derivative, whose bioavailability, limited by its very poor water-solubility, could be improved by cyclodextrin complexation. However, the choice of the most proper cyclodextrin to use to fully exploit its potential favourable effects on the drug, is a critical step. Therefore, in the present work, the performance of some amorphous cyclodextrin (CD) derivatives in terms of complexing, solubilizing and amorphizing power towards CLZ was carefully evaluated and compared with that of natural CDs.