Biomedical subjects

R Martínez-Pacheco

Publications and source records attributed to R Martínez-Pacheco.

At least 19 recordsLinked to original sources

PubMed2006

Compression behavior of formulations from Phyllanthus niruri spray dried extract.

The aim of this study was to evaluate the compression behavior of Phyllanthus niruri spray dried extract as well as the influence of excipients on the properties of tablets containing a high dose (70% by weight) of this product. The effect of excipients was studied by a 22 factorial design. The factors investigated were the type of disintegrant (croscarmellose sodium and sodium starch glycolate) and the type of filler/binder (microcrystalline cellulose and dibasic dicalcium phosphate). The tablets were produced on a single punch tablet press using a constant compression force of 5000 N. The tablets formulated with microcrystalline cellulose presented a plastic behavior while the tablets containing dibasic dicalcium phosphate disclosed a fragmentary behavior. The disintegration time was significantly influenced by both factors, however, the tensile strength was only affected by the filler/binder. Additional experiments considering the influence of the compression force (2500 N and 5000 N) and the proportion of croscarmellose sodium (1.5%, 3.0% and 6.0%) on the mechanical properties of the tablets were performed by a 2 x 3 factorial design. Both factors significantly affected the tensile strength, friability and disintegration time of the tablets.

Chemistry, Pharmaceutical↗

PubMed2005

A comparison of trehalose dihydrate and mannitol as stabilizing agents for dicalcium phosphate dihydrate based tablets.

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability. Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35 degrees C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Effect of microcrystalline cellulose grade and process variables on pellets prepared by extrusion-spheronization.

This study evaluated the effects of spheronizer load and speed on the size, circularity, microporosity, compressibility, and friability of pellets prepared by extrusion-spheronization of wet microcrystalline cellulose (MCC) masses with a water content shown by mixer torque rheometry to ensure maximum consistency. Two MCC grades with different mean particle size were used. Both gave pellets with good particle size, sphericity, and compressibility, under a wide range of spheronization conditions. Modification of pellet properties of interest (including size and porosity) was possible by adjustment of spheronization conditions and MCC grade; in particular, pellet porosity was greater with MCC of larger particle size.

Cellulose↗

PubMed2001

Extrusion-Spheronization of blends of carbopol 934 and microcrystalline cellulose.

We evaluated the effects of several process variables on the pharmaceutical and drug release properties of extrusion-spheronization pellets of blends of Carbopol 934 and microcrystalline cellulose (MCC) containing a high proportion of Carbopol. The model drug was theophylline. Rheological monitoring during mixing was by mixer torque rheometry. Carbopol:MCC blends wetted with a CaCl2 solution showed different rheological behavior compared to blends with a high proportion of MCC wetted with water only. In contrast to previous suggestions, the optimal wetting point for extrusion did not coincide with the point of peak torque, but occurred just beyond this point, at much lower torque. The influence of process variables on blend properties was investigated with a three-variable factorial design (Carbopol:MCC ratio, wetting liquid proportion, CaCl2:Carbopol ratio), and the influence of process variables on pellet properties with a four-variable design (the variables listed plus extrusion screen hole diameter). Blend torque values were strongly influenced by CaCl2 proportion, while mean pellet diameter was influenced by Carbopol:MCC ratio. Mean pellet diameter also differed depending on whether the pellets contained theophylline. The observed among-formulation differences in theophylline release kinetics were largely explained by differences in pellet size and theophylline hydration state. Compaction of pellets to form tablets markedly modified the drug release profile, making it biphasic.

Acrylates↗

PubMed2000

Evaluation of low-substituted hydroxypropylcelluloses (L-HPCs) as filler-binders for direct compression.

The aims of this study were to assess the potential value of low-substituted hydroxypropylcelluloses (L-HPCs) as excipients of direct compression, and to investigate relationships between the chemical and physical properties of the polymers and (a) the powder rheological behavior and (b) drug release profiles from direct compressed tablets elaborated with (1:1) theophylline:L-HPC mixtures. Experiments were performed with five L-HPC varieties of different nominal particle sizes and degree of substitution. The products were characterized with regard to the moisture content, density, IR and Raman spectroscopy, hydroxypropyloxy content, heat of hydration, particle size, specific surface and porosity, and important differences were found in relation with all these properties. The differences in specific surface principally determine the flow and compaction properties of the powders, and the mechanical and microstructural properties of the tablets. The control of the hydroxypropyloxy content and the particle size of the L-HPCs allow the theophylline release profile to be regulated.

Cellulose↗

PubMed2000

Interactions between hydroxypropylcelluloses and vapour/liquid water.

Understanding of the uptake of water vapour or liquid water by cellulose-based polymers is important because of the influence of these processes on many of the biologically or technologically relevant properties of these polymers. In this work we studied these processes in the cases of twelve hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively), characterization of which showed significant differences in structural and physical parameters (substitution pattern, crystallinity, particle size, specific surface area, and intraparticular porosity). Water vapour sorption-desorption isotherms determined to characterize the uptake of water vapour were fitted well by the Young-Nelson model, the optimized parameters of which indicated that at all relative humidities the capacity to bind water vapour as a surface monolayer is greater for HPCs than L-HPCs, but the capacity to absorb water vapour internally is greater for L-HPCs than HPCs. Guggenheim-Anderson-deBoer (GAB) models fitted the sorption-desorption isotherms less well. Differential scanning calorimetry (DSC) experiments showed all sorbed water vapour to be held as non-freezing water. Isoperibol microcalorimetry experiments carried out to investigate interactions with liquid water showed enthalpies of hydration/dissolution of between -62.86 and -71.35 J g(-1) for L-HPCs and between -82.95 and -99.80 J g(-1) for HPCs, and DSC showed average numbers of non-freezing water molecules per polymer repeat unit of 2.65-4.19 for L-HPCs and 18.10-22.42 for HPCs. DSC characterization of the kinetics of the water uptake by 10 mg compacts obtained by direct compression of hydroxypropylcelluloses showed faster uptake by L-HPC compacts than by HPC compacts, among which there were significant differences in capacity for diffusive uptake. The explanations of the above differences in terms of the different substituent contents, particle sizes and porosities of the HPCs is supported by multiple linear regression analyses.

Cellulose↗

PubMed2000

The stability of theophylline tablets with a hydroxypropylcellulose matrix.

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20 degrees C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).

Cellulose↗

PubMed2000

A comparison of cellactose with two ad hoc processed lactose-cellulose blends as direct compression excipients.

Three processed lactose-cellulose blends of similar composition, particle size and true density were compared as direct compression excipients: one was prepared by dry granulation, one by extrusion-spheronization, and the commercial product Cellactose. Differences among their flow properties depended solely on their different sphericities. Unlike those of the other blends, Cellactose particles exhibited numerous macropores. The mean yield pressures of all three blends were similar to those of direct compression lactoses. Cellactose tablets prepared at a punch pressure that largely eliminated macropores (pores >1 microm) had better mechanical properties but much poorer disintegration than tablets of the other blends prepared at the same punch pressure. However, the tensile strength and disintegration time of Cellactose tablets both fell rapidly as macropore volume was increased by reducing punch pressure, while the enthalpy of wetting/dissolution rose. The strength and water-resistance of well-compacted Cellactose tablets is attributed to the spatial distribution of lactose and cellulose in Cellactose particles, rather than to beta-lactose content or extra-particular structural features.

Cellulose↗

PubMed1999

Microviscosity of hydroxypropylcellulose gels as a basis for prediction of drug diffusion rates.

This study investigated the influence of the rheological properties of hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties (mean molecular weight between 5x105 and 1.2x106, nominal viscosity between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion coefficients at 37 degrees C ranged from 3.5x10-7 to 1.1x10-3 cm2/min, and were in all cases markedly higher than those predicted on the basis of gel macroviscosity as determined by capillary viscometry. In general, the theophylline diffusion coefficient declined exponentially with HPC concentration; in the case of the lowest-molecular-weight HPC, however, the diffusion coefficient remained constant to HPC concentrations of up to 0.8%, probably because of the high entanglement concentration of the HPC. Gel microviscosities as determined by dynamic light scattering (DLS) with latex microspheres (162 nm diameter) were considerably lower than the macroviscosities determined by capillary viscometry, and similar to microviscosities estimated on the basis of theophylline diffusion. Nevertheless, macroviscosity was correlated with microviscosity, suggesting that it is of value for approximate estimates of rates of diffusion of theophylline from HPC gels.

Cellulose↗

PubMed1999

Degradation of hydroxypropylcellulose by Rhizomucor: effects on release from theophylline-hydroxypropylcellulose tablets.

The stability of several varieties of hydroxypropylcellulose was monitored during 3 years of storage (1) under the conditions recommended by manufacturers and official pharmacopoeias (simple storage in closed containers) and (2) at zero relative humidity. After 1 year, severe degradation of the varieties with lower initial pH and particle size stored at ambient relative humidity was shown by changes in their molecular weight and in the pH and apparent viscosity of 2% aqueous dispersions. Microbiological analyses showed the observed degradation to be attributable to the action of fungi of the genus Rhizomucor. The changes in apparent viscosity significantly affected the release of theophylline from direct compression tablets formulated with the degraded excipients.

Cellulose↗

PubMed1999

A comparison of gas-liquid chromatography, NMR spectroscopy and Raman spectroscopy for determination of the substituent content of general non-ionic cellulose ethers.

This paper describes and compares three techniques that can be used to characterize the substituent content of hydroxypropylcellulose (HPC and L-HPC) and hydroxypropyl methylcellulose (HPMC): gas-liquid chromatography (GLC) with a BP1 column and FI detection, 13C-NMR spectroscopy of hydrolysed samples, and Raman spectroscopy. GLC and 13C-NMR spectroscopy both allow independent quantification of hydroxypropoxyl and methoxyl contents. 13C-NMR spectroscopy, though requiring lengthier sample preparation, has the advantage of also quantifying the degree of substitution at each substitutable glucopyranose hydroxyl. Raman spectroscopy may be useful for rapid approximate estimation of hydroxypropoxyl content.

Calibration↗

PubMed1999

Interfacial adsorption of polymers and surfactants: implications for the properties of disperse systems of pharmaceutical interest.

This review considers basic aspects of the interfacial adsorption of polymers and surfactants, with particular reference to the relevance of these processes for the formulation of pharmaceutical disperse systems. First, we discuss different approaches to the interpretation of adsorption isotherms, paying particular attention to systems containing more than one adsorbate. Second, we consider the implications of adsorption for the properties of suspensions, emulsions, and colloidal systems, particularly as regards the use of polymers and surfactants for stabilizing disperse systems, for controlling flocculation, and for modifying the biopharmaceutical behavior of colloidal drug carriers. Finally, we present a number of representative examples of the importance of adsorption of macromolecules in pharmaceutical systems.

Absorption↗

PubMed1998

The adsorption of cellulose ethers in aqueous suspensions of pyrantel pamoate: effects on zeta potential and stability.

This work examined the physico-chemical phenomena induced in aqueous suspensions of pyrantel pamoate by two varieties of hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) of different molecular weights, and the effects of these phenomena on the physical stability of the suspension. The mechanism of the interfacial adsorption of the polymer was investigated by constructing adsorption isotherms: for the two HPMC varieties, the isotherms were of type L and were fitted with the Langmuir model; of the NaCMCs, only the variety with higher molecular weight was adsorbed, its adsorption isotherm being of type S (sigmoidal). The resulting monolayer films were characterized viscosimetrically, determining their thickness and the number of polymer molecules adsorbed per unit area. The nonionic polymers formed thinner, more continuous monolayers than the NaCMC. Only the nonionic polymers significantly altered the zeta potential of the systems. In the range of conditions studied, all the polymers stabilized the initially flocculated systems, decreasing sedimentation volume and increasing the time necessary to redisperse them (the redispersability value). This stabilization occurred either by the steric mechanism (HPMCs and the high-molecular-weight NaCMC) or by depletion mechanisms (low-molecular-weight NaCMC). Owing to the complexity of these mechanisms, sedimentation volume was not found to be a useful index of the consistency of the sediments obtained from the suspensions.

Carboxymethylcellulose Sodium↗

PubMed1998

Development of tablets for controlled joint release of nifedipine and atenolol.

Oral combinations of nifedipine and atenolol are widely used in the treatment of hypertension, proving particularly effective when the atenolol is released immediately and the nifedipine is released in a sustained manner. This work examined the potential of combining nifedipine and atenolol in a tablet, which would be easier to manufacture than currently available combined formulations. The results indicated that a 40:60 (w/w) nifedipine-atenolol mixture forms a eutectic melting at 140 degrees C. Nevertheless, both drugs were stable when incorporated in tablets elaborated using cellulose ethers as base excipients. Tablets prepared from atenolol-lactose granules and solid dispersions of nifedipine-hydroxypropylmethylcellulose (100 cP) had more adequate dissolution profiles than a more complex reference formulation in hard capsules.

Atenolol↗

PubMed1997

Nifedipine/atenolol interactions in gastrointestinal absorption and biotransformation.

The combination of nifedipine and atenolol is widely used for the treatment of hypertension. In the present study, experiments performed in rats indicated that neither drug affects the gastric or intestinal absorption of the other. In assays of the biotransformation of nifedipine in liver homogenates, breakdown was much more rapid in homogenates from male rats than from female rats. In the presence of atenolol, the breakdown rate was significantly increased in homogenates from male rats, and significantly reduced in homogenates from female rats.

Adrenergic beta-Antagonists↗

PubMed1982

Quantification of the effect of excipients on bioavailability by means of response surfaces I: Amoxicillin in fat matrix.

A study was carried out to determine the effect of a fat excipient on the bioavailability of amoxicillin tablets. Three formulations with a fat excipient content of 10, 20, and 30%, respectively, were administered to 15 healthy volunteers according to a Latin-square design. The excretion curves were characterized with the help of two parameters, namely, the quantity of drug excreted between 0-2 and 0-12 hr postadministration, respectively. The effect of the fat excipient content was quantified with the use of polynomials whose corresponding orders were given by the ANOVA. In the case of both parameters, a quadratic response to the fat excipient content was found. At the same time, a dissolution study was carried out using a previously established method. Here, the parameters used to characterize the dissolution curves were the quantities of dissolved drug in 30 and 180 min, respectively. Again, a quadratic response to the fat excipient content was observed in the case of both parameters.

Adult↗

PubMed1982

Quantification of the effect of excipients on bioavailability by means of response surfaces II: Amoxicillin in fat-silica matrix.

This report studies the bioavailability of amoxicillin in different fat-silica matrixes. A urinary excretion study was carried out on four formulations containing fat and silica excipients. The formulations were administered to 24 healthy volunteers according to a Latin-square design. The following percent proportions of fat-silica were used: 15:3.75, 15:7.50, 30:3.75, and 30:7.50. The urinary excretion curves were characterized using the quantity of unchanged drug excreted between 0-2 and 0-12 hr postadministration, respectively as parameters. The ANOVA results showed that both excipients had an additive effect on the quantity of drug excreted between 0 and 2 hr, whereas the effect on the quantity of drug excreted between 0 and 12 hr was also one of interaction between both excipients. Quantification of the ANOVA results in terms of excipient content was conducted by means of the adequate linear functions. At the same time, a dissolution study was carried out using the quantity of drug dissolved in 30 and 180 min as parameters. The behavior was similar to that encountered for the in vivo parameters.

Adolescent↗

PubMed1982

Quantification of the effect of excipients on bioavailability by means of response surfaces III: In vivo--in vitro correlations.

This study compares one of the previously studied formulations with commercial amoxicillin capsules. The results indicate that the percentage of the dose absorbed is similar in both formulations; nevertheless, the amoxicillin capsules present a higher absorption rate. The in vivo--in vitro correlations in terms of response surfaces, and the general correlation among all the formulations studied in the three articles of this series is discussed. The quantity of drug excreted in 2 hr and the quantity of drug dissolved in 30 min presents a correlation coefficient r = 0.9458 (p less than 0.01) and the quantity of amoxicillin excreted in 12 hr and the quantity dissolved in 180 min presents a correlation coefficient r = 0.9761 (p less than 0.01).

Adolescent↗