ß-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions.

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous ß-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous ß-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and ß-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on ß-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems.

Porous calcium phosphate pellets were produced according to two granulation processes (low and high shear wet granulations) and drug loaded with five ibuprofen contents (1.75%, 7%, 12.5%, 22%, and 36%) in order to ensure both bone defect filling and local drug delivery. The drug-release kinetics from the two types of pellets was studied using three dissolution apparatuses: paddle apparatus, reciprocating cylinder, and flow-through cell. The paper compared the three dissolution methods and considered the effect of the granulation process on the ibuprofen-release kinetics. Dissolution data were analyzed using the Weibull function as well as the difference (f1) and similarity (f2) factors. Dissolution kinetics was not influenced by the granulation process, regardless of the dissolution apparatus and of the drug content. The comparison of the three dissolution devices indicated that ibuprofen was released faster from granules loaded with 36% of drug content with the reciprocating apparatus, due to the disintegration of the granules occurring during the dissolution test. For the other drug contents, dissolution profiles were not significantly different from one apparatus to another. However, the flow-through cell seemed to be more suitable for the drug-release study of implantable materials.

Dissolution of a surfactant-containing active porous material.

We have studied the imbibition and dissolution of a porous material in two separate scenarios: (1) when the porous material contains a surfactant powder and (2) when the porous material is dissolved in a surfactant solution. We show that the dissolution kinetics in both scenarios is significantly affected by the presence of the surfactant and results in an increase in the characteristic imbibition time of the porous material, which can be well understood in the framework of the classical law of capillarity. Slowing of the imbibition kinetics was found to be affected by a modification of the liquid wetting properties, but is also affected by a variation in the solubility of the porous material in the presence of the surfactant. Furthermore, there is a depletion effect of the surfactant inside the rising liquid, which is in good agreement with previous work and theoretical predictions.

Fabrication of porous substrates: a review of processes using pore forming agents in the biomaterial field.

This paper is a review of solid and casting manufacturing processes able to create porous materials, mainly in the biomaterial field. The considered methods are based on pore forming agents that are removed either by heating or by dissolution. All techniques lead to products presenting pores with amount, size, and shape are close to those of the initial pore formers. Porosities up to 90% with pores ranging from 1 to 2000 microm are reported. Major differences concern macrointerconnections that are more frequently obtained using foams, or porogens which undergo a melting stage during firing. Casting methods combined with solid free form fabrication are promising for the design of porous network through the manufacturing of 3D scaffolds corresponding to the desired porosity.

Powder functionality test: a methodology for rheological and mechanical characterization.

In most pharmaceutical formulations, the part of the excipients, in quantity and number, is larger than that of active principles, justifying particular attention to their characteristics to ensure quality, efficacy, and reproducibility of final forms. Whereas chemical specifications are described in Pharmacopeias, physical characteristics, up to now, have not been sufficiently considered. Nevertheless, there is a need for tests to objectively compare technological performances of products and justify composition of medicinal products. The powder functionality test described in this article is based on the analysis of the global behavior of materials under pressure. The powder compression is performed using an instrumented uniaxial press, Lloyd 6000R, and a compression cell of 1 cm3 in volume, allowing a complete and early characterization with a few grams of material. Indices characterizing packing, densification energies, energetic yields, and deformation mode of the particles are proposed from the analysis of compression cycles. Cohesion and energy of rupture are deduced from the diametral rupture cycles of the compacts. Application of this methodology to supplied celluloses has shown better flow properties of microcrystalline celluloses due to their higher bulk density and particle size. The energy fraction lost as frictions is very important and independent of the type of celluloses, whereas elastic energy is higher for powdered celluloses P100 and G250. Finally the efficacy to convert compaction energy into cohesion is higher for products with a small degree of polymerization, i.e., microcrystalline celluloses, except A301 and A302, which also are distinguished by their low porosity.