Correlation Between the Transdermal Permeation of Ketoprofen and its Solubility in Mixtures of a pH 6.5 Phosphate Buffer and Various Solvents

The passage of a drug through the skin is directly proportional to the concentration of the drug in the donor phase and to the permeability coefficient constant Kp. Kp is determined essentially by two factors: the dissolution of the drug in the stratum corneum (measured by the partition coefficient P) and the diffusion in the same stratum (measured by the diffusion constant D). In our study, several saturated solutions of ketoprofen in mixtures of a pH 6.5 phosphate buffer and various co-solvents were studied to find correlations between the solubility of the ketoprofen in the mixtures and its permeation parameters in in vitro permeation studies with Franz cells. The results show that D does not change in the different mixtures; the diffusion of the drug into the stratum corneum is not influenced by the presence of the co-solvents, whereas the partition coefficient is strongly influenced. In particular, Kp and P were found to be inversely proportional to solubility, meaning that when the co-solvent increases the solubility, the partition of the drug and consequently Kp decrease. These findings were confirmed in some developed gels, and the developed gels were found to enhance the ketoprofen permeation with respect to the formulation in a commercial Fastum gel

Design and evaluation of buccal adhesive hydrocortisone acetate (HCA) tablets.

Many studies have shown that topical buccal therapy with steroid anti-inflammatory drugs is useful in controlling ulcerative and inflammatory mucosal diseases. This local treatment is based on the concept that a high activity of steroids can be produced at the site of administration and, at the same time, the degree of systemic side effects can be minimized or avoided. In this study we developed a new formulation consisting of a mucoadhesive tablet formulation for buccal administration of hydrocortisone acetate (HCA). Three types of tablet were developed containing three mucoadhesive components: hydroxypropylmethyl cellulose (Methocel K4M), carboxyvinyl polymer (Carbopol 974P), and polycarbophyl (Noveon AA1); the first polymer is a cellulose derivative, the others are both polyacrylic acid derivatives. For each of those, three tablet batches were produced changing the quantity of the mucoadhesive component (10, 20, and 30%), resulting in 9 different formulations. The compatibility of HCA with all excipients using Differential Scanning Calorimetry (DSC) was assessed. Tablets were manufactured by wet granulation followed by compression. Technological controls on granulates (Hausner index, Carr index, granulometry and Karl-Fischer percentage humidity) and tablets (thickness, diameter, friability, hardness, uniformity of content, weigh uniformity and dissolution kinetic) were carried out. Mucoadhesion properties, ex vivo permeability through porcine buccal mucosa, in vivo behavior and compliance were evaluated. Technological controls have demonstrated that the increase in the (percentage) of mucoadhesive causes an increase in granulometry followed by a reduction in the granulate flowability, however all the tablets have given satisfactory technological results and conformed to the 3rd Ed. European Pharmacopoeia specifications. Mucoadhesion, ex vivo permeability and in vivo behavior results notably differed among tablets, depending on the quality and quantity of the mucoadhesive component. An overall comparison of results showed the tablets containing Carbopol 20% resulted to be the best formulation among those developed

Honos alit artes. Studi per il settantesimo compleanno di Mario Ascheri. Gli universi particolari

Le ricerche confluite nel volume, dovute a storici di diversa vocazione, illustrano svariati aspetti della storia dell’Italia medievale e moderna (ordinamenti, economia, società, istituzioni ecclesiastiche e civili, architettura, arte, urbanistica); sono incentrate sulle singole realtà cittadine e su circoscritte aree geografiche e politiche. Fra queste, particolare attenzione è riservata alla città di Siena e al suo territorio, che costituiscono uno dei centri di interesse dell’illustre studioso al quale è dedicata la serie di quattro volumi di cui fa parte il presente

Honos alit artes. Studi per il settantesimo compleanno di Mario Ascheri. L’età moderna e contemporanea. Giuristi e istituzioni tra Europa e America

Gli studi compresi nel volume analizzano la storia giuridica e sociale dell’Europa e dell’America settentrionale dalla fine del Settecento all’età contemporanea. I filoni della riflessione riguardano il rapporto tra cultura giuridica e stato (scienza, legislazione e governo), l’amministrazione della giustizia e la trasformazione delle professioni forensi. È ovviamente presente la faglia di separazione che individua, nel complesso della tradizione giuridica occidentale, i paesi di Common law

Honos alit artes. Studi per il settantesimo compleanno di Mario Ascheri. Il cammino delle idee dal medioevo all’antico regime

I saggi riuniti nel volume seguono, attraverso una lunga serie di approfondimenti monografici, molte svolte cruciali della storia del pensiero giuridico e politico europeo, sia nella prospettiva del diritto comune (civile e canonico) sia in quella dei diritti particolari dei singoli ordinamenti. All’analisi di aspetti più strettamente teorici si affiancano disamine di concrete e specifiche esperienze; si studiano inoltre vicende di libri e testi, come elementi di sollecitazione del dibattito culturale

<i>Honos alit artes</i>. Studi per il settantesimo compleanno di Mario Ascheri. II. Gli universi particolari

The researches accounted in the volume, being reported by historians who had different vocations, illustrate various aspects of medieval and modern history (laws, economy, society, church and civil institutions, architecture, art, urban planning); they are focused on single town realities and limited geographical-political areas. Among these, particular attention ought to be given to the city of Siena and its territory, which constitute one of the centres of interest for the illustrious scholar to whom is dedicated the series of four volumes, which the present also belongs to

Solubility and Transdermal Permeation Properties of a Dehydroepiandrosterone Cyclodextrin Complex from Hydrophilic and Lipophilic Vehicles

The permeation ability of a compound is due principally to its concentration in the vehicle and to its aptitude to cross the stratum corneum of the skin. In this work ex-vivo permeation studies on newly developed formulations containing dehydroepiandrosterone (DHEA) were carried out to investigate vehicles that increase drug permeation through the skin. To enhance the solubility of DHEA, its complex form with alpha-cyclodextrin was used. In addition, the two forms (pure drug and complex form) were introduced in hydrophilic (water), lipophilic (paraffin oil), and microemulsion vehicles to evaluate the synergic effect of cyclodextrins and microemulsion vehicles on solubility and permeation. From the results, DHEA solubility is notably conditioned by the type of the vehicle used: the highest solubilities (both for pure and complex drug forms) were obtained with microemulsion, followed by paraffin oil and water. Moreover, in all the studied vehicles, the c-DHEA was more soluble than DHEA. Permeation profile fluxes showed very interesting differences. That reflect the varying drug forms (pure drug and complex form), vehicles used, and drug concentrations in the vehicles. The major flux was obtained in complex of DHEA with alpha-cyclodextrins in the microemulsion vehicle. Therefore, this type of vehicle and drug form would be very useful in the development of a topical formulation containing DHEA

Mucoadhesive tablets for buccal administration containing sodium nimesulide.

The possibility of improving the flux of nimesulide across the buccal mucosa using the drug in the form of a sodium salt was investigated in our study. The salt form may increase to flux across buccal membrane, starting from a suspension; its lower permeation coefficient is compensated by a higher concentration gradient. The salt was inserted into a mucoadhesive tablet for buccal administration. The tablets were designed to prevent the loss of the drug into the saliva by means of a protective layer and placed on the area not in contact with the mucosa. Ten volunteers were used. The in vitro release from mucoadhesive tablets was examined through a porcine buccal mucosa, using a standard Franz cell, modified for present purposes. The advantages of a higher concentration gradient for the flux, related to a higher solubility of the salt, and to a sufficiently high permeation coefficient of the drug, despite the ionized form, could not be completely exploited, because the composition of the formulation destroys the chemical form of the drug