Biomedical subjects

G Vergnault

Publications and source records attributed to G Vergnault.

3 recordsLinked to original sources

PubMed2006

Matrices containing NaCMC and HPMC 1. Dissolution performance characterization.

In this study hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used as polymeric carriers to improve controlled release performances of matrix tablets containing a soluble drug. The drug release behaviour of the systems containing these two polymers mixture and each material separately was investigated. To evaluate the effect of the dissolution medium pH, on the drug release performance, release tests were conducted at pH 1, 4.5 and 6.8. In vitro release studies demonstrated that the mixture of the two cellulose derivatives enables a better control of the drug release profiles at pH 4.5 and at 6.8 both in term of rate and mechanism. Texture analysis on the swollen tablets helps to understand drug release kinetic and mechanism. In fact, the results obtained confirm that a gel, which is characterized by high strength and consistence is less susceptible to erosion and chains disentanglement and the drug release mechanism is mainly governed by diffusion. On the contrary, gels, which show a low strength and texture, have low resistance to the fluid erosion action and the release of the active molecule is manly due to polymer relaxation and chains disentanglement moving the drug delivery kinetic towards an erosion/relaxation mechanism.

Carboxymethylcellulose Sodium↗

PubMed2005

Nanosuspension formulations for low-soluble drugs: pharmacokinetic evaluation using spironolactone as model compound.

Various particle sizes of spironolactone as a model low solubility drug were formulated to yield micro-and nanosuspensions of the type solid lipid nanoparticles and DissoCubes. Seven oral and one i.v. formulations were tested in an in vivo pharmacokinetic study in rats with the aim of characterizing the bioavailability of spironolactone on the basis of its metabolites canrenone and 7-alpha-thiomethylspirolactone. In addition, a dose escalation study was carried out using nonmicronized spironolactone suspension as well as a nanosuspension type DissoCubes. On the basis of AUC as well as Cmax ratios, three groups of formulations were distinguished. The biggest improvement was seen with a solid lipid nanoparticle formulation yielding a 5.7-fold increase in AUC for canrenone and a similar improvement based on the Cmax metric, followed by a group of three formulations containing nanosized, micronized, and coarse drug material and surfactant. The DissoCubes nanosuspension yielded highly significant improvements in bioavailability averaging 3.3-fold in AUC and 3.0-fold in terms of Cmax for canrenone. The third class encompasses all other formulations, which showed very little to no improvement in bioavailability. The results show that the particle size minimization was not the major determining factor in the bioavailability improvement. Rather, the type of surfactant used as stabilizer in the formulations was of greater importance. Improvement in drug solubility in the intestine as well as in dissolution rate of spironolactone are the most likely mechanisms responsible for the observed effect, although additional mechanisms such as permeability enhancement may also be involved.

Administration, Oral↗

PubMed2002

Power of experimental design studies for the validation of pharmaceutical processes: case study of a multilayer tablet manufacturing process.

Experimental design studies (EDS) are already widely used in the pharmaceutical industry for drug formulation or process optimization. Rare are the situations in which this methodology is applied for validation purposes. The power of this statistical tool, key element of a global validation strategy, is demonstrated for a multilayer tablet manufacturing process. Applied to the Geomatrix system generally composed of one compression and three granulation processes, time and strictness gains are non-negligible. Experimental design studies are not used in this work for modeling. Introduced at each important step of the process development, they allow for the evaluation of process ruggedness at pilot scale and specifications for full production. A demonstration of the complete control of key process parameters is given, identified throughout preliminary studies.

Chemistry, Pharmaceutical↗