A new polysaccharidic gel matrix for drug delivery: preparation and mechanical properties
A new polysaccharidic gel matrix for drug delivery: preparation and mechanical properties
Received 21 July 2004; accepted 25 October 2004. Available online 24 November 2004.
Tommasina Covielloa, , , Franco Alhaiquea, Chiara Parisia, Pietro Matricardia, Gianfranco Bocchinfusob and Mario Grassic
Journal of Controlled Release
Volume 102, Issue 3 , 16 February 2005, Pages 643-656
aDipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Universit? ?La Sapienza?, P.le A .Moro 5, 00185 Rome, Italy
bDipartimento di Scienze e Tecnologie Chimiche, Universit? di Roma ?Tor Vergata?, Via della Ricerca Scientifica, 00133 Rome, Italy
cDipartimento di Ingegneria Chimica, dell'Ambiente e delle Materie Prime, Universit? di Trieste, P.le Europa 1, 34127 Trieste, Italy
A new type of hydrogel was prepared, under controlled conditions, by diffusion of Ca(II) ions into a solution of the carboxylated derivative of Scleroglucan (Sclerox). The obtained hydrogel was loaded with Theophylline (TPH) and Myoglobin (MGB), two model drugs of remarkably different steric hindrance, and also used, after freeze drying, for the preparation of tablets. Release studies were carried out on both the freshly prepared gel and on the tablets.
As far as the gel systems experiments are concerned, the delivery profiles resulted to be deeply dependent on the molecular dimensions of the loaded molecules; TPH was easily released while the larger tested molecule (MGB) remained partially entrapped within the three-dimensional network. Furthermore, in the case of MGB, the release was dependent also on polymer concentration (cp): at the highest investigated cp value a corresponding lowest delivery of the guest molecule was observed. This effect of polymer concentration on the rate of delivery was studied applying three different mathematical approaches: the one that better fitted the experimental release profile allowed to support the explanation of the mechanism involved in the observed two-step delivery that has been related to the drug trapping inside the clusters of the gel network.
The delivery profiles from the tablets showed how the release, in this case, could be related, essentially, to the molecular dimensions of the guest molecules, independently on the cp used to prepare the starting hydrogel. TPH was completely delivered in a few hours while the MGB was almost unable to diffuse out of the matrix and more than 80% resulted entrapped in the network for at least 24 h.
The novel hydrogel, at different cp, was also characterized by means of a texture analyzer to inspect its mechanical properties.
According to the compression data, the hardness, the work of cohesion and the work of adhesion of the networks were estimated. Furthermore, by means of relaxation experiments, analysed applying the generalized Maxwell model, the gels can be classified as solid viscoelastic materials and the mechanical spectra indicated a predominance of the viscous behaviour, while the Young modulus, E0, as expected, was found to increase with polymer concentration.
Keywords: Scleroglucan derivative; Hydrogel; Theophylline; Myoglobin; Modified release; Texture Analyzer
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