Biomedical subjects

P Mura

Publications and source records attributed to P Mura.

At least 19 recordsLinked to original sources

PubMed2006

Differential scanning calorimetry as a screening technique in compatibility studies of DHEA extended release formulations.

Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of DHEA as ternary complex with alpha-cyclodextrin and glycine (c-DHEA) with some excipients suitable for preparation of sustained-release matrix tablets by direct compression. The effect of sample mechanical treatment due to the compression process was also evaluated. In order to investigate the possible interactions between the components, the DSC curves of c-DHEA and each selected excipient were compared with those of their 1:1 w/w physical mixtures, before and after compression, in order to evaluate any possible solid state modification. FT-IR spectroscopy and X-ray powder diffractometry were used as complementary techniques to adequately implement and assist in interpretation of the DSC results. On the basis of DSC results, c-DHEA was found to be compatible with xanthan gum, hydroxypropylmethylcellulose, sodium starch glycolate (Explotab), polyvinylacetate-polyvinylpirrolidone (Kollidon SR) and sodium chloride. Some drug-excipient interaction was observed with dextrate hydrate (Emdex), mannitol and Magnesium stearate. Finally, the behaviour of the complete formulation, in the presence of all the excipients selected by means of the compatibility study, was investigated, in order to verify the absence of reciprocal interactions among the components.

Calorimetry, Differential Scanning↗

PubMed2006

Simultaneous effect of cyclodextrin complexation, pH, and hydrophilic polymers on naproxen solubilization.

The effect of pH variation on complexation and solubilization of naproxen (pK(a) 4.2) with natural betaCyclodextrin (betaCyD) and various neutral, cationic and anionic betaCyD-derivatives has been investigated. The combined effect of pH variation and hydrophilic polymer addition on CyD solubilizing and complexing efficiency has also been determined. Phase-solubility analysis in buffered aqueous solutions (pH from 1.1 to 6.5) was used to study the interaction of the drug with each CyD, in the presence or not of the water-soluble polymer. A clear influence of the substituent type was observed, the methylderivative being the most efficient agent; on the contrary, unexpectedly, no influence of the CyD charge in the interaction with the ionizable drug was detected. As expected, total drug solubility increased with increasing pH; however, the solubility increment with respect to drug alone obtained by CyD complexation progressively decreased, with a parallel reduction of the complex stability, attributed to the reduced affinity of charged drug for the hydrophobic CyD cavity. The addition of the polymer in part counterbalanced the destabilizing effect obtained with increasing pH, by improving the CyD complexation power towards naproxen. In particular, the presence of PVP allowed an increase of the complex stability constant with hydroxypropyl betaCyD up to 60% with respect to the corresponding drug-CyD binary system. Therefore, the combined strategy of pH control and polymer addition to the CyD complexing medium can be successfully exploited to improve naproxen solubilization and reduce the amount of CyD needed. The construction of theoretical drug solubility curves as a function of pH for any given CyD and polymer concentration enables selection of the best experimental conditions for obtaining the desired drug solubility value.

Hydrogen-Ion Concentration↗

PubMed2006

[Cannabis and road crashes: a survey of recent French studies].

The clarification of the mechanisms of action of cannabis and its effects on motor and cognitive functions, the results of previous studies performed on driving simulators and closed or open-road driving trials, are important criteria for highlighting the increased risk of road crashes for drivers after a recent use of cannabis. In addition epidemiological studies allow to measure the magnitude of the problem. A survey of French epidemiological studies performed from 1999 to 2004, as well as the data of THC distribution in tissues studies performed on man and animal allowed us to draw a number of conclusions. The risk of road crash after a recent use of cannabis is increased by more than 2.4 in all studies. The prevalence of cannabis use in drivers involved in a road crash has dramatically increased during the last years. For methodological reasons (a too high threshold for THC positivity, a too long time delay between accident and blood sampling), the annual number of fatal cases induced by a cannabis use was likely underestimated. This assessment is consistent with recent data which indicate that THC could be still present in brain while absent in blood. A positivity threshold for THC in blood of 0.5 ng/mL would be more appropriated. So, all recent French studies highlighted that a recent use of cannabis impairs driving ability and that it would be advisable to intensify roadside testing for drugs of abuse.

Accidents, Traffic↗

PubMed2005

Use of drugs of abuse in less than 30-year-old drivers killed in a road crash in France: a spectacular increase for cannabis, cocaine and amphetamines.

A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

Accidents, Traffic↗

PubMed2005

Influence of cyclodextrins and chitosan, separately or in combination, on glyburide solubility and permeability.

The effect of chitosan and of different concentrations of beta- or hydroxypropyl-beta-cyclodextrins, separately or in various (w/w) combinations, on the dissolution characteristics of glyburide (an oral hypoglycemic agent subject to incomplete and variable bioavailability) and on its permeability through Caco-2 cells has been investigated. Cyclodextrins (and particularly the hydroxypropyl-derivative, in virtue of its higher water solubility) were clearly more effective than chitosan in enhancing the drug dissolution properties: the aqueous glyburide solubility was improved 40-fold in the presence of 25 mM hydroxypropyl-beta-cyclodextrin, 25-fold in the presence of 13 mM beta-cyclodextrin (saturation solubility) and only 3-fold in the presence of chitosan at its saturation concentration (0.5% w/v). When chitosan and cyclodextrin were simultaneously present, a strong reduction of the cyclodextrin solubilizing efficiency towards the drug was observed, and it was attributed to a possible competition effect of polymer and glyburide for the interaction with the macrocycle. By contrast, permeation studies revealed that chitosan was more powerful than cyclodextrins in enhancing the glyburide permeability through Caco-2 cells. This was probably in virtue of the polymer's favourable effect on the tight junctions opening, as demonstrated by the significant decrease in the transepithelial electrical resistance recorded in its presence. Moreover, interestingly, when using the carriers together, conversely from solubility studies, a significant (P < 0.05) synergistic effect in enhancing glyburide apparent permeability was revealed in permeation experiments.

Algorithms↗

PubMed2005

Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

Acrylic Resins↗

PubMed2005

Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state.

The possible role of the cyclodextrin charge in the interaction with an acidic drug such as naproxen (pKa 4.8) has been evaluated. Sulfobutylether-beta-cyclodextrin (SBE-betaCyd) and trimethylammonium-beta-cyclodextrin (TMA-betaCyd) were selected as, respectively, anionically and cationically charged carriers and their performance was compared with that of the parent beta-cyclodextrin (betaCyd) and of its methyl-derivative (Me betaCyd) previously found as the best partner for the drug. Interactions in solution were investigated by phase-solubility, fluorescence and circular dichroism analyses. Equimolar drug-carrier products prepared by different techniques (blending, cogrinding, sealed-heating, colyophilization) were characterized by differential scanning calorimetry and X-ray powder diffractometry and tested for drug dissolution properties. Anionic charges of SBE-betaCyd did not negatively influence interactions in unbuffered aqueous solutions (pH approximately 5) with the acidic drug. In fact, it was a very effective carrier, exhibiting solubilizing and complexing properties considerably better than the parent betaCyd and comparable to those of Me betaCyd. On the contrary, the positive charges of TMA-betaCyd did not favour interactions with the counter-ionic drug (despite the presence of about 60% ionised drug) and it was less efficacious also than native betaCyd. Therefore, the role of the Cyd charge on the complexing and solubilizing properties towards naproxen was not important whereas other factors, such as steric hindrance effects and favourable hydrophobic interactions were significant in determining the drug affinity for the Cyd inclusion. Solid state studies evidenced similar amorphizing properties of both charged Cyds towards naproxen. On the other hand, dissolution tests, in agreement with solution studies, showed that all products with SBE-betaCyd exhibited significantly better dissolution properties than the corresponding ones with TMA-betaCyd. A clear influence of the preparation method of drug-Cyd solid systems on the performance of the end product was also observed. Colyophilization was the most effective technique, followed by the cogrinding one. Colyophilized product with SBE-betaCyd allowed a 10-times increase in drug dissolution efficiency (D.E.) (with respect to the five-times increase obtained with the corresponding coground product) and a reduction of t(50%) from about 60 min (for the coground product) to less than 2 min.

Cyclodextrins↗

PubMed2005

Determination of stability constant values of flurbiprofen-cyclodextrin complexes using different techniques.

Three new experimental approaches for calculating the stability constant (K(st)) of complexes of flurbiprofen with natural beta-cyclodextrin (betaCyd) and the hydroxyethyl- (HEbetaCyd) and the methyl- (Me betaCyd) derivatives were tested and compared to the classic phase-solubility procedure: (a) the membrane permeation technique through a lipophilic synthetic membrane permeable to the drug but not to the Cyd molecules, by analysing the permeation profiles with a non-linear least-squares method; (b) the affinity capillary electrophoresis (ACE) technique, where K(st) were calculated from the relationship between Cyd concentration in solution and drug electrophoretic mobility, using three different linear plotting methods; (c) the molecular modeling technique, based on the relationship between the docking energies and the experimental K(st) values. The study allowed evaluation of the advantages and limits of each examined method, providing a useful guide for the choice of the most suitable one depending on the kind of host-guest system to be investigated. The K(st) values obtained with the various techniques were rather different, probably due to the very different experimental conditions required by each one. However, all the methods indicated the methyl-derivative as the most powerful complexing agent for the drug, showing the general trend: K(st)(Me betaCyd)>>K(st)(HEbetaCyd)>K(st)(betaCyd). Only in the case of the ACE method was an inversion of the trend found between HEbetaCyd and betaCyd; this was probably due to the lower molecular weight of the natural Cyd, which, in this case, became more important in determining the complex electrophoretic mobility than the different affinity of the drug for these two Cyds.

Chemistry, Pharmaceutical↗

PubMed2005

Optimization of glibenclamide tablet composition through the combined use of differential scanning calorimetry and D-optimal mixture experimental design.

A systematic analysis of the influence of different proportions of excipients on the stability of a solid dosage form was carried out. In particular, a d-optimal mixture experimental design was applied for the evaluation of glibenclamide compatibility in tablet formulations, consisting of four classic excipients (natrosol as binding agent, stearic acid as lubricant, sorbitol as diluent and cross-linked polyvinylpyrrolidone as disintegrant). The goal was to find the mixture component proportions which correspond to the optimal drug melting parameters, i.e. its maximum stability, using differential scanning calorimetry (DSC) to quickly obtain information about possible interactions among the formulation components. The absolute value of the difference between the melting peak temperature of pure drug endotherm and that in each analysed mixture and the absolute value of the difference between the enthalpy of the pure glibenclamide melting peak and that of its melting peak in the different analyzed mixtures, were chosen as indexes of the drug-excipient interaction degree.

Calorimetry, Differential Scanning↗

PubMed2005

Characterization and dissolution properties of ketoprofen in binary and ternary solid dispersions with polyethylene glycol and surfactants.

The effect of incorporation of an anionic [sodium dodecyl sulfate (SDS) or dioctylsulfosuccinate (DSS)] or nonionic [Tween 60 (TW60)] surfactant on the properties of ketoprofen solid dispersions in polyethylene glycol 15000 (PEG) has been investigated. Physicochemical and morphological properties of the various solid systems were determined by differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction analysis, and scanning electron microscopy. The results from dissolution studies, performed according to the USP 24 basket method, indicated that all ternary dispersed systems were significantly (p < 0.001) more efficacious than the corresponding binary ones, by virtue of the additive wetting and solubilizing effect due to the presence of the surfactant. The relative effectiveness of the incorporated surfactant was in the same order as found in phase-solubility studies (i.e., SDS > DSS > TW60). With regard to the solid dispersion preparation method, coevaporated products always gave better results than the corresponding cofused ones; however, this effect was statistically significant (p < 0.001) only in the initial phase of the dissolution process. The most effective solid dispersion was the 10-80-10 w/w drug-PEG-SDS ternary coevaporate, which allowed dissolution of 50% drug after only 6 min (in comparison with > 120 min for drug alone and 17 min for the binary coevaporate) and dissolution of about 100% drug after 30 min (in comparison with > 120 min for the binary coevaporate).

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Photostability studies on nicardipine-cyclodextrin complexes by capillary electrophoresis.

Nicardipine (NC)-cyclodextrin solid systems were prepared in equimolar ratios and their photostability in aqueous solution under exposure to UV(A)-UV(B) radiations was evaluated. The photodegradation process was monitored by a capillary electrophoresis (CE) method able to provide the enantioresolution of the rac-nicardipine. Enantioresolution was achieved using the mixture 3.0% sulfate-beta-cyclodextrin (SbetaCD) and 2.0% heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD) as chiral selector in 20mM triethanolammonium phosphate solution (pH 3.0). The photostability studies were carried out on inclusion complexes of rac-nicardipine with alpha-cyclodextrin (alphaCD), beta-cyclodextrin (betaCD), gamma-cyclodextrin (gammaCD), hydroxypropyl-alpha-cyclodextrin (HPalphaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), hydroxypropyl-gamma-cyclodextrin (HPgammaCD), (2-hydroxyethyl)-beta-cyclodextrin (HEbetaCD) and methyl-beta-cyclodextrin (MbetaCD). A photoprotective effect was observed by betaCD, HPalphaCD, HEbetaCD, whereas gammaCD, MbetaCD, HPbetaCD and HPgammaCD did not affect the nicardipine photostability. Conversely, alphaCD was found to favour the drug photodegradation. Evidences for CDs-mediated stereoselective photodegradation of rac-nicardipine were observed only for the beta-CD complex. In this case, two distinct photodegradation profiles, with two different kinetic constants (k), were observed for the nicardipine enantiomers.

Biotransformation↗

PubMed2004

Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells.

Chitosan and its glutamate and hydrochloride salts were evaluated for their efficacy in improving the dissolution behaviour of naproxen (a poorly water-soluble antiinflammatory drug) and its transport in vitro across Caco-2 cell monolayers. Drug-polymer physical mixtures and coground products, prepared at two different w/w ratios (30/70 and 10/90), were characterized by differential scanning calorimetry, X-ray powder diffractometry, scanning electron microscopy, and tested for dissolution properties. Coground systems were more effective than physical mixtures in improving drug dissolution and chitosan base, in spite of its lower water solubility, showed higher solubilizing power than its salts. According to the solid state analyses results, this effect was directly related to its stronger amorphizing power. Transport studies showed that only coground mixtures with chitosan glutamate salt allowed a significant drug apparent permeability improvement; however, they did not exhibit appreciable effects on the Caco-2 tight junctions (measured by the trans-epithelial electrical resistance variations), thus indicating that their enhancer effect was mainly due to an improved naproxen transport by transcellular passive diffusion rather than through the paracellular route. The direct compression properties and antiulcerogenic activity together with the demonstrated dissolution and permeation enhancer abilities toward naproxen make chitosan glutamate an optimal carrier for developing fast-action oral solid dosage forms of this drug.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

[Usefulness of biological markers in the evaluation of smoking at the first visit of a smoking cessation program].

INTRODUCTION: We have studied the relationship between urinary cotinine and other tobacco markers to assess the relevance of urinary cotinine in the dosage of nicotine substitutes. METHODS: One hundred and fifty-five patients, who were regular cigarette smokers not taking any nicotine substitutes took part in the study. The parameters examined were daily consumption, nicotine contents of the cigarettes, the Fagerström test score, levels of carbon monoxide (CO) in exhaled breath air and urinary cotinine. RESULTS: The most significant correlation was between urinary cotinine and exhaled CO (Spearman rs=0,59 p<0,001). The correlation between urinary cotinine, the Fagerström test (rs=0,32 p<0,001) and daily cigarette consumption (rs=0,32 p<0,001) was less significant. The nicotine content was not related to urinary cotinine (rs =-0,10NS). CONCLUSIONS: For economic reasons measuring urinary cotinine is not necessary when the CO level is or=35 ppm. It becomes useful if the CO level is between 15 and 34 ppm, as CO level in itself is insufficient to determine the dosage of nicotine substitutes.

Adolescent↗

PubMed2004

Formulation and characterization of triclosan sub-micron emulsions and nanocapsules.

Triclosan, a non-ionic, broad spectrum anti-microbic agent, has recently demonstrated its effectiveness as an anti-malarial drug by inhibition of the growth of Plasmodium Falciparum. The aim of this work was to formulate suitable triclosan colloidal carriers with the final objective of obtaining a drug delivery system suitable for a potential anti-malarial oral treatment. Two different nanotechnological approaches were experimented with that could be suitable for developing effective triclosan formulations against this established and re-emerging infectious disease. Sub-micron emulsions were prepared by the solvent displacement method, using different oily amounts in order to vary the drug amount entrapped in the formulation. Chitosan-coated nanocapsules were obtained with chitosan hydrochloride at two different viscosity degrees (Cl 113 and Cl 213). All formulations were appropriately characterized by determining drug loading capacity and encapsulation efficiency and measuring particle size and zeta potential. Morphological characterization of the different systems was performed by TEM analysis, whereas release studies were carried out by reverse bag dialysis method. All preparations resulted stable. Cl 113-coated nanocapsules appeared particularly suitable as triclosan carriers for obtaining a systemic drug release, owing to both chitosan's good mucoadhesive and enhancer properties as well as the effectiveness shown by its coating in adequately controlling drug release rate.

Antimalarials↗

PubMed2004

Development of enteric-coated timed-release matrix tablets for colon targeting.

A new oral drug delivery system for colon targeting has been developed based on enteric-coated matrix tablets which suitably exploits both pH-sensitive and time-dependent functions. Matrix-tablets were prepared by direct compression of mixtures of hydroxyethylcellulose (HEC), a hydrophilic swellable polymer, with the inert insoluble ethylcellulose (EC) or micro-crystalline cellulose (MCC) polymers, in which theophylline, selected as model drug, was dispersed. Eudragit S100, a methacrylic acid copolymer soluble at pH 7, was used as pH-sensitive coating polymer. The influence of varying the cellulose-derivative combinations and their relative ratios as well as the level of the coating polymer was investigated. Surface morphology of the tablets was monitored by SEM analysis before and after the release test. The results of release studies, performed according to the USP basket method using a sequence of dissolution media simulating the gastrointestinal physiological pH variation, indicated that the Eudragit S100 enteric-coated matrix tablets were successful in achieving gastric resistance and timed-release of the drug, assuring an adequate lag time for the intended colonic targeting, followed by a controlled-release phase. The enteric-coating level emerged as the critical factor in determining the duration of the lag-phase, whereas the release rate mainly depended on the matrix composition. Formulations with higher HEC content showed a faster drug release rate than those with greater content in inert polymer and the MCC-HEC combinations were more effective than the corresponding EC-HEC ones. The best results were given by the 27% coated 1:0.3:0.7 (w/w) drug/MCC/HEC tablets, which, after a 260 min lag time, regularly released the drug, achieving about 90% of release after 10 h.

Chemistry, Pharmaceutical↗

PubMed2004

Characterization of ibuproxam binary and ternary dispersions with hydrophilic carriers.

This work investigates the possibility of increasing the dissolution properties of ibuproxam (a poorly water-soluble anti-inflammatory drug) using hydrophilic carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), or urea, alone or in combination. Phase-solubility studies showed that the carrier solubilizing power was in the order PEG>PVP>urea and evidenced a synergistic effect in drug solubility improvement when using carrier combinations. Binary and ternary systems, at 20/80 or 20/40/40 (w/w) drug/carrier(s) ratios, prepared by coevaporation of their ethanolic solutions or by cogrinding physical mixtures in a high-energy vibrational micromill, were characterized by differential scanning calorimetry (DSC), hot stage microscopy (HSM), and scanning electron microscopy (SEM) analyses. The results of dissolution tests (USP paddle method), in terms of Dissolution Efficiency, indicated that ternary systems were up to 35% more effective than the corresponding binary preparations and coevaporated products were up to 45% more efficacious than the corresponding coground ones. The IBUX-PEG-PVP coevaporated was the best product, allowing a more than three-times increase in Dissolution Efficiency with respect to drug alone; moreover, t50% (> 60 min for pure ibuproxam) was < 10 min, and 90% dissolution was achieved after 30 min, whereas only 40% was obtained after 60 min for pure drug. The best performance of this system was attributed to a joined effect of the strong amorphizing power of PVP (as demonstrated by solid state analyses) with the high solubilizing efficacy of PEG (as emerged from phase-solubility studies). The drug dissolution rate from solid dispersions remained practically unchanged after one-year storage at room temperature in closed containers.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique.

Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 microm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage.

Calorimetry, Differential Scanning↗

PubMed2003

How experimental design can improve the validation process. Studies in pharmaceutical analysis.

A critical discussion about the possibility of improving the method validation process by means of experimental design is presented. The reported multivariate strategies concern the evaluation of the performance parameters robustness and intermediate precision, and the optimisation of bias and repeatability. In particular, accuracy and precision improvement constitutes a special subset of experimental design in which the bias and the relative standard deviation of the assay are optimised. D-optimal design was used in order to plan experiments for this aim. The analytical methods considered were capillary electrophoresis, HPLC, adsorptive stripping voltammetry and differential pulse polarography. All methods were applied to real pharmaceutical analysis problems.

Adsorption↗