Naslov
Preparation and characterisation of bupivacaine-hydrochloride-cyclodextrin complexes aimed for buccal drug delivery

Autori
Mario Jug, Francesca Maestrelli, Giulia Mitola, Paola Mura

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
II Congresso nazionale chimica e technologia delle ciclodextrine, abstract book / Trotta, Francesco - Asti, 2009, IV-P2

Skup
II Congresso nazionale chimica e technologia delle ciclodextrine

Mjesto i datum
Asti, Italija, 03.05.2009. - 05.05.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
bupivacaine hydrochloride; beta-cyclodextrin-epychlorhydrin polimer; solid state analysis; dissolution rate; buccal delivery

Sažetak
Bupivacaine hydrochloride (BVP HCl) is an amide type local aesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade [1]. In this study we have prepared and characterised solid binary systems of BVP HCl and different cyclodextrins with the aim to suitably modify its biopharmaceutical properties, and thus to develop an effective novel formulation intended for buccal drug delivery. The selected cyclodextrins were native beta-cyclodextrin (beta-CD) and its soluble polymer beta-cyclodextrin epichlorohydrin (EPI-beta-CD). The solid binary systems were prepared by different techniques, i.e. physical mixing, ball-milling in high-energy vibrational mills, coevaporation and lyophilisation, in order to rationally select the most effective method. The solid products obtained were characterised by thermal (DSC) and spectral (FTIR and XRPD) analyses. The influence of the preparation method used on the physicochemical properties of the plain drug was also evaluated. Results of solid-state studies revealed more intense interactions of BVP HCL with EPI-beta-CD than with the native one, accompanied by stronger reduction of drug crystallinity in the samples, probably favoured by the amorphous nature of the polymeric carrier. Moreover, while summarising the results of DSC and XRPD analyses, it appears that ball-milling of drug/cyclodextrin binary mixtures was particularly efficient in inducing effective solid-state interactions between the components and it can be considered as the method of choice for preparation of complexes of BVP HCl with beta-CD and EPI-beta-CD. Other advantages of this method include low cost, absence of solvent, and short preparation times. In vitro dissolution properties of ball-milled plain drug and corresponding complexes in artificial saliva were investigated simulating the conditions that are present at the surface of the buccal mucosa. Limited amount of the dissolution medium and the existence of an unstirred aqueous layer were recognised as the most important parameters. In such conditions, the dissolution rate of the drug was limited, resulting in dissolution of only 23.3 % of the drug dose after 1.5 h. The inclusion complex formation with EPI-beta-CD increased the amount of dissolved drug by 1.3 times, while the complex with beta-CD was characterised by reduced drug dissolution rate. It may be concluded that complexation of BVP HCl with beta-CD and EPI-beta-CD is a suitable tool for properly tailoring the dissolution properties of BVP HCl in conditions similar to those present at the surface of the buccal mucosa and it can be favourably exploited for the development of an effective buccal drug delivery system. 1. Moraes et al., Int. J. Pharm., 331 (2007), 99

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA