Engineering poly(ethylene oxide) buccal films with cyclodextrin: a novel role for an old excipient?

Inspired by the multiple roles cyclodextrins can play in polymeric systems, here we engineered poly(ethylene oxide) (PEO) films with (2-hydroxypropyl)-ß-cyclodextrin (CD) as multipurpose ingredient. To shed light on the potential of CD in formulating PEO buccal films for the delivery of poorly water-soluble drugs, we preliminarily assessed thermal and mechanical properties as well as wettability of films prepared at different PEO/CD ratios. PEO/CD platform containing 54% by weight of CD was chosen as the optimized composition since it matched acceptable mechanical properties, in terms of tensile strength and elasticity, with a good wettability. The platform was tested as buccal delivery system for triamcinolone acetonide (TrA), a lipophilic synthetic corticosteroid sparely water soluble. Confocal Raman imaging clearly showed that CD was homogeneously (i.e. molecularly) dispersed in PEO. Nevertheless, homogenous drug distribution in the film without TrA crystallization occurred only in the presence of CD. Finally, CD-containing PEO film placed in simulated buccal fluids provided a useful speed-up of TrA release rate while showing slower dissolution as compared to PEO film. These results, as well as compliance with quality specifications of pharmaceutical manufacturing products, strongly support the soundness of the strategy and prompt toward further applications of PEO/CD films in buccal drug delivery.

Local delivery of the hemostatic agent tranexamic acid in chronically anticoagulated patients.

In oral surgery, the management of patients on anticoagulant therapy is still challenging because of the risks of uncontrolled bleeding and, if the therapy is discontinued, the possibility of undesired thromboembolic complications. The use of local hemostatic agents may be a viable alternative to overcome these issues. Along these lines, the aim of this work was to evaluate the use of newly developed swelling matrices loaded with tranexanic acid in preventing postextractive bleeding in patients with no modification of oral anticoagulant therapy. The matrices are made up of cellulose and are able to fit the tridimensional postextractive alveolar cavity, thus assuring also a mechanical contribution to homeostasis. The potential of this new therapeutic approach in reducing hospitalization, removing the risk of infections, and lowering the number of hemorrhagic complications was demonstrated.

Modulation of release rate and barrier transport of Diclofenac incorporated in hydrophilic matrices: role of cyclodextrins and implications in oral drug delivery.

The aim of this work was to investigate how the incorporation of a hydrophilic cyclodextrin (CD) inside erodible hydrophilic matrices affects drug-release behavior and transport properties through artificial and biological membranes. To this purpose, Diclofenac (Dic) was incorporated in poly(ethyleneoxide) (PEO) matrices as poorly soluble free acid (DicH) or freely water-soluble sodium salt (DicNa) in the presence or absence of hydroxypropyl-beta-cyclodextrin (HP beta CD). Preliminary experiments demonstrated that HP beta CD increased Dic apparent solubility as a function of its amount in the solution and medium pH due to complex formation. Permeation of ionized Dic through porcine buccal mucosa gave higher values of J(SS) and K(p) as compared to silicon membranes and depended on the presence of HP beta CD. Incorporation of HP beta CD in PEO tablets resulted in an increase of release rate for both forms of Dic whereas cumulative drug flux through silicon membranes and porcine buccal mucosa was increased for DicH and decreased for DicNa. An interpretation of this behavior was attempted on the basis of the presence of a transport resistance occurring inside the hydrated gel matrix as modified by the presence of CD. In conclusion, this study has demonstrated that the use of CDs in hydrophilic matrices intended for oral drug delivery should be rationalized since their modulator effect relies not only on drug-dissolution rate but also on environment where drug release occurs (aqueous medium, membrane interface).