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

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

L’avvio al lavoro della persona con disabilità nella prospettiva dei Servizi specialistici di mediazione. Gli esiti di un percorso di formazione e ricerca

L'articolo esplora il complesso tema del lavoro per le persone con disabilità. Nell'analisi della situazione italiana si evidenziano gli elementi da monitorare affinché attraverso l'accesso al lavoro venga promossa l'emancipazione generale del soggetto, nell'ottica della Convenzione ONU sui diritti delle persone con disabilità. A supporto di modalità operative evidence-based, vengono presentati i risultati di una ricerca-azione svolta con gli operatori della mediazione del lavoro dell'Azienda ULSS di Treviso.The article explores the complex field of employment for people with disabilities. In the analysis of the Italian situation, the elements to be monitored are highlighted so that through access to work an overall emancipation of the person is promoted, in the perspective of the UN Convention on the rights of persons with disabilities. In support of evidence-based operating methods, the results of an action-research carried out with labor mediation operators are presented

Control of Transdermal Permeation of Hydrocortisone Acetate from Hydrophilic and Lipophilic Formulations

The purpose of this research was the preparation of four formulations containing hydrocortisone acetate (HCA) for topical application, including two aqueous systems (hydrophilic microemulsion and aqueous gel) and two systems with dominant hydrophobicity (hydrophobic microemulsion and ointment). The formulations were tested for the release and permeation of HCA across an animal membrane. The release of HCA was found comparable for the four systems. The two microemulsions promote permeation across an ex-vivo membrane, examined by means of a Franz cell. Hydrophobic microemulsion guarantees the highest solubility (2,370 μg/ml) and flux (133 μg/cm2.h) of the drug, since it contains almost 40% Transcutol, a permeation enhancer. Gel and ointment provide lower solubility and flux, being the values, related to the ointment, the lowest ones (562 μg/ml and 0.4 μg/cm2.h). Experimental results allow the conclusion that gel and ointment can be suitable when it is desirable to minimize absorption of topically applied HCA as to keep the drug restricted to the diseased area and prevent side effects of the systemic presence of HCA

Razvoj i in vitro vrednovanje puferiranog bioadhezivnog vaginalnog gela za miješane vaginalne infekcije

An acid buffering bioadhesive vaginal (ABBV) gel was developed for the treatment of mixed vaginal infections. Different bioadhesive polymers were evaluated on the basis of their bioadhesive strength, stability and drug release properties. Bioadhesion and release studies showed that guar gum, xanthan gum and hydroxypropylmethylcellulose K4M formed a good combination of bioadhesive polymers to develop the ABBV gel. Mono sodium citrate was used as an acid buffering agent to provide acidic pH (4.4). The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as antibacterial) were used in the formulation along with Lactobacillus spores to treat mixed vaginal infections. The ex vivo retention study showed that the bioadhesive polymers hold the gel for 12-13 hours inside the vaginal tube. Results of the in vitro antimicrobial study indicated that the ABBV gel had better antimicrobial action than the commercial intravaginal drug delivery systems and retention was prolonged in an ex vivo retention experiment.U radu je opisan razvoj puferiranog biodhezivnog vaginalnog (acid buffering bioadhesive vaginal, ABBV) gela za terapiju miješanih vaginalnih infekcija. Ispitani su različiti bioadhezivni polimeri procijenjena su njihova bioadhezivna svojstva, stabilnost i sposobnost oslobađanja ljekovite tvari. Guar guma, ksantan guma i hidroksipropilmetilceluloza K4M tvore dobru kombinaciju za ABBV gel. Mono natrijev citrat upotrebljen je kao puferirajuća tvar koja omogućava blago kiseli pH (4,4), a kao ljekovite tvari upotrebljeni su klotrimazol (antimikotik) i metronidazol (antiprotozoik i antibakterijsko sredstvo), zajedno sa sporama Lactobacillus. Pripravci su upotrebljeni u terapiji miješanih vaginalnih infekcija. Pokusi ex vivo pokazali su da se bioadhezivni gel zadržava u vagini 12-13 sati. Rezultati in vitro ispitivanja ukazuju na to da ABBV gel ima bolje antibakterijsko djelovanje i dulje zadržavanje od intravaginalnog sustava koji je dostupan na tržištu

[Blood sugar control in children and young diabetics during an educational summer camp]

PEDIATR MED CHI

Design and evaluation in vitro of controlled release mucoadhesive tablets containing chlorhexidine.

This investigation deals with the development of buccal tablets containing chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects in the oral cavity, and able to adhere to the buccal mucosa to give local controlled release of drug. A mucoadhesive formulation was designed to swell and form a gel adhering to the mucosa and controlling the drug release into the oral cavity.Some batches of tablets were developed by direct compression, containing different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing the amount ratio of these excipients in formulations, it is possible easily modulate the mucoadhesive effect and release of drug. The in vitro tests were performed using the USP 26/NF paddle apparatus, a specifically developed apparatus, and a modified Franz diffusion cells apparatus. This last method allows a simultaneous study of drug release rate from the tablets and drug permeation through the buccal mucosa.Similar tests have also been carried out on a commercial product, Corsodyl gel, in order to compare the drug release control of gel with respect to that of the mucoadhesive tablet, as a formulation for buccal delivery of CHX. While the commercial formulation does not appear to control the release, the formulation containing 15% w/w methocel behaves the best, ensuring the most rapid and complete release of the drug, together with a negligible absorption of the active agent as required for a local antiseptic action in the oral cavity