Biomedical subjects

Angel Concheiro

Publications and source records attributed to Angel Concheiro.

At least 19 recordsLinked to original sources

PubMed2007

Sustained release pellets based on poly(N-isopropyl acrylamide): matrix and in situ photopolymerization-coated systems.

The usefulness of poly(N-isopropyl acrylamide), PNIPA, for preparing sustained release matrix or photopolymerization-coated cellulosic pellets was evaluated. Theophylline pellets and granules were prepared using powdered cellulose (PC), poly(vinylpyrrolidone) (PVP), and PNIPA of Mw approximately 330 kDa, Mn approximately 93 kDa and low critical solubility temperature approximately 32 degrees C. The low consistency of wet mass, evaluated by torsion rheometry, due to hydrophilic character of PNIPA at room temperature, favored extrusion-spheronization. Theophylline (20%) pellets prepared with 15% PNIPA, 20% PVP and 45% PC, and granules obtained using 40% PNIPA and 40% PC showed an enhanced, although limited, ability to sustain the release. This effect was notably promoted after compression (which provides slowly eroding tablets) or coating of individualized pellets. A new coating technique consisting in forming the polymer film by photo-polymerization/cross-linking of NIPA monomers on pellets surface, using a photoinitiator and UV-irradiation at 366 nm, was developed. The composition of coating mixture and the time of irradiation were optimized using oscillatory rheometry. Coating did not significantly change the shape, size, or friability of the pellets but remarkably decreased the porosity and sustained drug release for several hours. In situ formation and cross-linking of PNIPA on the pellet appears as a feasible way for controlling drug release.

Acrylamides↗

PubMed2007

Improving the loading and release of NSAIDs from pHEMA hydrogels by copolymerization with functionalized monomers.

Poly(hydroxyethyl methacrylate), pHEMA, hydrogels are widely used for preparing implants, contact lenses, and other biomedical devices, which in many circumstances should load drugs to deliver them in the adjacent tissues. To enhance the potential of pHEMA hydrogels as nonsteroidal anti-inflammatory drugs (NSAIDs) delivery systems, 4-vinyl-pyridine (VP) and N-(3-aminopropyl) methacrylamide (APMA) were incorporated to the network (25-150 mM). The incorporated monomers did not change the viscoelastic properties neither the state of water, but remarkably increased the amount of ibuprofen (up to 10-fold) and diclofenac (up to 20-fold) loaded. Dried loaded pHEMA-APMA and pHEMA-VP hydrogels quickly swelled in water but ionic/hydrophobic interactions prevented the amount of drug released to be above 10%. By contrast, once the water-swollen hydrogels were transferred to pH 5.8 or 8.0 phosphate buffers or NaCl solutions, the release was prompted by competition with ions of the medium. The remaining of hydrophobic interactions and the high polymeric density of the pHEMA hydrogels contributed to sustain the release process for at least 24 h for ibuprofen and almost 1 week for diclofenac. The release rate was independent of the salt content and pH in the physiological range of values, which enables the design of hydrogel-based delivery systems with predictable release rate.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

New cyclodextrin hydrogels cross-linked with diglycidylethers with a high drug loading and controlled release ability.

PURPOSE: The goal of the study is to develop new hydrogels based on cyclodextrins cross-linked with ethyleneglycol diglycidylether (EGDE) under mild conditions, to be used as carriers of amphiphilic drugs. Also, it aims to characterize the cross-linking and the drug loading and release processes. METHODS: The cross-linking of hydroxypropyl-beta-cyclodextrin (HPbetaCD) with EGDE, in the absence or presence of hydroxypropylmethylcellulose (HPMC) Methocel K4M, was optimized applying oscillatory rheometry and Fourier transform infrared. Hydrogels were characterized regarding swelling in water, ability to load diclofenac, and release after different drying treatments. RESULTS: Solutions of HPbetaCD (14.28%), without or with HPMC (0.2-1.0%), provided firm and transparent hydrogels after cross-linking with EGDE (14.28%), in which around two thirds of the OH groups were cross-linked. The incorporation of HPMC progressively reduced the gel time and the swelling degree of hydrogels. HPbetaCD hydrogels efficiently loaded diclofenac and sustained the release for several hours. The presence of HPMC slowed the release from swollen hydrogels, but promoted it from hydrogels dried before the loading and also before the release. CONCLUSIONS: HPbetaCD hydrogels with good mechanical properties and tunable loading and release ability can be obtained by direct cross-linking with EGDE.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2006

Tetronic micellization, gelation and drug solubilization: Influence of pH and ionic strength.

The aim of this work was to gain an insight into the self-associative processes and drug solubilization ability of a Tetronic variety, T904 (4 x 15 EO units; 4 x 17 PO units; HLB 15), in aqueous media covering the physiological range of pH and ionic strength, applying isoperibol microcalorimetry, transmission electronic microscopy (TEM), dynamic light scattering (DLS), oscillatory rheometry, and drug diffusion experiments. T904 shows two pK(a) (pK(a1)=4.0 and pK(a2)=7.9) and, at pH<5.8, the diprotonated form predominates over the non-protonated one. Deprotonization of the central diamine group is a required condition for micellization, which is an endothermic entropy-driven process owing to hydrophobic interactions between the PPO chains. As the pH of the solutions decreases, the coulombic repulsions among the positively charged amine groups make the aggregation more difficult, raising the critical micellar concentration (CMC) and decreasing the size of the micelles. The changes in the conformation and hydrophilicity of the Tetronic were reflected in its gelation temperature (around 30 degrees C at neutral-alkaline pH; no gelation at pH<2) and solubilization capacity for griseofulvin (2-fold greater at neutral-alkaline pH than at pH<2) and rate of diffusion (slower at pH 7.4). Such alterations in self-assembly are relevant when using Tetronic in the design of drug delivery systems.

Calorimetry↗

PubMed2006

Imprinted soft contact lenses as norfloxacin delivery systems.

Soft contact lenses are receiving an increasing attention not only for correcting mild ametropia but also as drug delivery devices. To provide poly(hydroxyethyl methacrylate), PHEMA, lenses with the ability to load norfloxacin (NRF) and to control its release, functional monomers were carefully chosen and then spatially ordered applying the molecular imprinting technology. Isothermal titration calorimetry (ITC) studies revealed that maximum binding interaction between NRF and acrylic acid (AA) occurs at a 1:1, and that the process saturates at 1:4 molar ratio. Hydrogels were synthesized using different NRF:AA molar ratios (1:2 to 1:16), at two fix AA total concentrations (100 and 200 mM), and using moulds of different thicknesses (0.4 and 0.9 mm). The cross-linker molar concentration was 1.6 times that of AA. Control (non-imprinted) hydrogels were prepared similarly but with the omission of NRF. All hydrogels showed a similar degree of swelling (55%) and, once hydrated, presented adequate optical and viscoelastic properties. After immersion in 0.025, 0.050 and 0.10 mM drug solutions, imprinted hydrogels loaded greater amounts of NRF than the non-imprinted ones. Imprinted hydrogels synthesized using NRF:AA 1:3 and 1:4 molar ratios showed the greatest ability to control the release process, sustaining it for more than 24 h. These results prove that ITC is a useful tool for the optimization of the structure of the imprinted cavities in order to obtain efficient therapeutic soft contact lenses.

Acrylates↗

PubMed2006

Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability.

The influence of the proportion of acrylamidomethyl-gamma-cyclodextrin (gamma-CD-NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. gamma-CD-NMA was synthesized by condensation of gamma-cyclodextrin (gamma-CD) with N-(hydroxymethyl) acrylamide. Hydrogels were prepared with gamma-CD-NMA and sodium acrylate (3 M or 4 M), using N,N'-methylen(bisacrylamide) (BIS) as cross-linker, by free radical polymerization into glass moulds of 2 mm wide and were cut as discs (10 mm diameter). gamma-CD-NMA did not modify the pH-dependent swelling of the hydrogels, but significantly increased the swelling degree in the 40:60 ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with gamma-CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without gamma-CD-NMA. This is explained by the formation of 1:1 inclusion complexes of TA with gamma-CD mers that overcomes the lack of interactions with the acrylic groups of the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer was sustained for at least 24 h, whatever the pH and the composition of the medium used. In contrast, loading of PR from the water solutions was greater for hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to their content in gamma-CD-NMA, and in less than 2 h ca. 80% PR was released. The lower affinity of PR for the gamma-CD cavities, compared to the strong intensity of the electrostatic interactions with the acrylic acid groups, explains why the incorporation of gamma-CD-NMA did not increased the loading and control release capacity of the hydrogels of this hydrophilic drug. In summary, the copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH-sensitive networks which load large amounts of hydrophobic drugs and release them in a sustained way.

Calorimetry, Differential Scanning↗

PubMed2006

Sertaconazole/hydroxypropyl-beta-cyclodextrin complexation: isothermal titration calorimetry and solubility approaches.

Complexation of sertaconazole (SN) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was characterized by phase-solubility diagram measurements and isothermal calorimetry (ITC) in aqueous medium, and by differential scanning calorimetry (DSC), Raman spectroscopy and X-ray diffractometry in solid state. The strongest interaction was observed at pH 1.2, at which two different 1:1 complexes can be formed depending on the hydrophobic ring of the drug involved in the process. At pH 5.8 and 7.4 the likelihood of 1:2 stoichiometry increases as a consequence of the simultaneous complexation of the nonprotonized imidazolyl and the dichlorophenyl groups. In the presence of 20% HP-beta-CD, SN solubility is enhanced by a factor of 116, 107, and 5 at pH 1.2, 5.8, and 7.4, respectively. Complexation enthalpy recorded by ITC showed the same tendency which confirms the practical interest of this technique for fast screening of the potential of CDs as drug solubilizers. Solubility and dissolution rate of the drug from compacts prepared with freeze-dried complexes were significantly greater than those obtained with SN powder or compacts made with physical blends.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2006

Molecularly imprinted materials as advanced excipients for drug delivery systems.

The application of the molecular imprinting technology in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors or biological traps, is receiving increasing attention. Molecular imprinting technology can provide polymeric materials with the ability to recognize specific bioactive molecules and with a sorption/release behaviour that can be made sensitive to the properties of the surrounding medium. In this review, an introduction to the imprinting technology presenting the different approaches in preparing selective polymers of different formats is given, and the key factors involved in obtaining of imprinted binding sites in materials useful for pharmaceutical applications are analysed. Examples of DDS based on molecularly imprinted polymers (MIPs) can be found for the three main approaches developed to control the moment at which delivery should begin and/or the drug release rate; i.e., rate-programmed, activation-modulated or feedback-regulated drug delivery. This review seeks to highlight the most remarkable advantages of the imprinting technique in the development of new efficient DDS as well as to point out some possibilities of adapting the synthesis procedures to create systems compatible with both the relative instable drug molecules, especially of peptide nature, and the sensitive physiological tissues with which MIP-based DDS would enter into contact when administered. The prospects for future development are also analysed.

Biotechnology↗

PubMed2005

Pluronic-g-poly(acrylic acid) copolymers as novel excipients for site specific, sustained release tablets.

Potential utility of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (PAA) as excipients for sustained-release tablets was explored. Apparent particle density, particle size distribution, Carr index, thermal stability, and compression behavior of the Pluronic-PAA copolymers were characterized. Tablets prepared by direct compression of blends of Pluronic-PAA copolymers were evaluated on the basis of their thermomechanical profile, crushing strength, friability, and drug release properties. Small molecular weight drugs of aqueous solubility decreasing in the order theophylline>hydrochlorothiazide>nitrofurantoin were incorporated to the tablets. For comparison purposes, tablets were also prepared from PAA of Carbopol 71G (C71G), and mixtures of C71G and Pluronic F127, with each of the above three drugs. The Pluronic-PAA aggregates are stabilized by hydrophobic associations between poly(propylene oxide) (PPO) segments in aqueous solutions, and thus require higher ionization of the carboxylic groups to overcome the associations and swell. The swelling pattern of the Pluronic-PAA copolymers is more dramatically pH-dependent than that of Carbopol lacking any hydrophobic associations. The drug retention in and release from the Pluronic-PAA based tablets is profoundly pH-dependent and hence specific to the pH exceeding that of the pK(a)>5 of these copolymers. Theophylline- and hydrochlorotiazide-containing tablets made with Pluronic-PAA copolymers showed a reduced release rate under acidic conditions compared to the neutral or alkaline conditions, while the opposite pattern was observed with the Carbopol-based tablets due to the different pH-dependent swelling behavior of the polymers. Nitrofurantoin-containing tablets showed a remarkably low drug release rate owing to the strong hydrophobic character of nitrofurantoin and of its complexes with the copolymers. Integrity of the nitrofurantoin-containing tablets was maintained during the 24h release test. Zero-order kinetics of the cumulative release profile of all drugs under study was observed with the Pluronic-PAA as a tablet excipient. Adequate mechanical properties, the self-assembling behavior, and the pH-sensitiveness of the Pluronic-PAA copolymers make them promising excipients for tablets with preferential delivery into a neutral to alkaline pH environment.

Acrylic Resins↗

PubMed2005

Biophysical characterization of complexation of DNA with block copolymers of poly(2-dimethylaminoethyl) methacrylate, poly(ethylene oxide), and poly(propylene oxide).

The interactions of DNA (salmon testes) with two new cationic block copolymers made of poly(2-dimethylaminoethyl) methacrylate and poly(ethylene oxide), PEO-pDMAEMA, or poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), L92-pDMAEMA, were studied with the aim to understand their different in vitro transfection efficiencies when used as nonviral delivery vectors. PEO-pDMAEMA does not show surface activity while L92-pDMAEMA is as surface active as its parent Pluronic L92. Surface tension, titration microcalorimetry, ethidium bromide displacement, and zeta-potential measurements were carried out in phosphate buffers at pH 5 and 7. The association of L92-pDMAEMA with DNA was strongly exothermic at both pHs; the critical aggregation concentration (CAC) corresponded to a N/P ratio of 0.3, the maximum energy evolved was reached for N/P ratios of 0.82 and 1.27 at pH 5 and pH 7, respectively, and the saturation occurred for N/P ratios close to 2. The presence of L92 in the structure of this new block copolymer apparently did not modify the thermodynamic parameters of the interaction with DNA. In contrast, the interaction with PEO-pDMAEMA was significantly less exothermic, and CAC and saturation occurred for N/Ps equal to 0.43 and 1.37, respectively. The strong affinity of L92-pDMAEMA for DNA was reflected in its capacity to displace ethidium bromide and in the jump in the values of the zeta potential when N/P is near 1. Above the N/P ratio at which electroneutral polyplexes are formed, only at pH 5 an excess of L92-pDMAEMA is incorporated in the complexes, resulting in positively charged complexes. The profile of the zeta-potential values obtained for mixtures of L92-pDMAEMA with Pluronic P123 showed a shift to a lower N/P ratio, owing to an easier interaction of L92-pDMAEMA molecules with DNA in the presence of P123. Additionally, a visual inspection of the systems indicates that P123 contributes to stabilize/solubilize the DNA/cationic polymer aggregates, by avoiding the typical phase separation near the charge neutralization point. The information obtained can be particularly useful to optimize the conditions to form efficient polyplexes for gene delivery systems.

Animals↗

PubMed2005

Temperature-sensitive chitosan-poly(N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties.

Interpenetrated polymer networks (IPN) of poly(N-isopropylacrylamide) (PNIPA) and chitosan (two grades) were prepared by free radical polymerisation and cross-linking of PNIPA (700 mM) with bis(acrylamide) (20 mM) in chitosan solutions (1.5 wt.% in acetic acid), and subsequent immersion in glutaraldehyde solutions (0 to 0.7 vol.%) to post-cross-link the chitosan. The amount of chitosan that remained in the IPNs, after washing, was proportional to the glutaraldehyde concentration used in the post-cross-linking step; being only 50% of the theoretical when the post-cross-linking was omitted (semi-IPN). The temperature-induced phase transitions of the IPNs were followed by the changes in the swelling degree and in the thermodynamic parameters (temperature, enthalpy, heat capacity, and width of the transition), which were evaluated using high-sensitivity differential scanning calorimetry (HS-DSC). An increase in the post-cross-linking degree of chitosan caused a decrease in the enthalpy of the transition, and in the absolute value of the transition heat capacity increment (delta(t)C(p)), as well as a broadening of the heat capacity peak. This behaviour is a consequence of the subdivision, in the IPNs, of the PNIPA network in microdomains, some regions of which (surface or outer) cannot be involved in the transitions. On the other hand, changes in pH from 8 to 3 only increased the transition temperature from about 32 to 34 degrees C, despite the considerable modification that this caused in the ionisation degree of chitosan. The PNIPA/chitosan IPNs had a notably greater affinity for diclofenac than the pure PNIPA hydrogel and were able to sustain the drug release for more than 8 h in 0.9% NaCl solutions or pH 8 phosphate buffer. The IPNs with lower chitosan post-cross-linking degree showed the higher temperature-sensitive release patterns. In contrast, the temperature did not significantly affect the release rate from the most cross-linked IPNs, in which the PNIPA microdomains are smaller and the volume phase transitions are less sharper. Therefore, PNIPA microdomains play an important role in controlling the release process. In summary, the interpenetration of networks with complementary properties, such as those made with PNIPA and chitosan, make it possible to develop drug delivery systems with improved drug loading capacity (owing to chitosan) and sustained release behaviour (owing to PNIPA).

Acrylic Resins↗

PubMed2004

Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly(acrylic acid) copolymers.

The capability of a family of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (Pluronic-PAA) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was studied. The unprotected lactone form of CPT, which possesses cytotoxic activity, is rapidly converted to the ring-opened carboxylate form under physiological conditions. Firstly, surfactant properties such as critical micellization concentration (CMC) of Pluronic-PAA copolymers were characterized. Then, the equilibrium solubility partitioning and hydrolysis of the lactone form of CPT in the presence of Pluronic-PAA in water and in human serum were analyzed. CPT solubility in polymer micellar solutions was ca. 3- to 4-fold higher than that in water at pH 5. The amount of CPT solubilized per PPO was considerably greater in the Pluronic-PAA solutions than in the parent Pluronic solution, which suggests that the drug is not only solubilized by the hydrophobic cores and also by the hydrophilic POE-PAA shells of the micelles. The equilibrium partition coefficient of the CPT lactone between Pluronic-PAA solutions and water exceeded (2-3) x 10(3). The complete solubilization of CPT and the absence of chemical interactions between CPT and Pluronic-PAA were confirmed by modulated temperature differential scanning calorimetry (MTDSC), infrared spectroscopy, and X-ray diffraction of films. The loading of CPT into the Pluronic-PAA micelles was able to prevent the hydrolysis of the lactone group of the drug for 2 h at pH 8 in water. When compared to the unprotected CPT, the kinetics of the CPT hydrolysis in human serum was about 10-fold slower in the Pluronic-PAA formulations.

Acrylic Resins↗

PubMed2004

Molecularly imprinted polymers for drug delivery.

Molecular imprinting technology has an enormous potential for creating satisfactory drug dosage forms. Although its application in this field is just at an incipient stage, the use of MIPs in the design of new drug delivery systems (DDS) and devices useful in closely related fields, such as diagnostic sensors, is receiving increasing attention. Examples of MIP-based DDS can be found for the three main approaches developed to control the moment at which delivery should begin and/or the drug release rate, i.e. rate-programmed, activation-modulated, or feedback-regulated drug delivery. The utility of these systems for administering drugs by different routes (e.g. oral, ocular or transdermal) or trapping undesired substances under in vivo conditions is discussed. This review seeks to highlight the more remarkable advantages of the imprinting technique in the development of new efficient DDS as well as pointing out some possibilities to adapt the synthesis procedures to create systems compatible with both the relative instable drug molecules, especially of peptide nature, and the sensitive physiological tissues with which MIP-based DDS would enter into contact when administered. The prospects for future development are also analysed.

Drug Delivery Systems↗

PubMed2004

Modulating drug release with cyclodextrins in hydroxypropyl methylcellulose gels and tablets.

This paper reports on the effect of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the diffusion and the release behavior of diclofenac sodium and sulphamethizole from HPMC K4M gels and matrix tablets. The gels were prepared with 0.5-2.0% polymer and different drug/CD mole ratios, and their viscosity, cloud point and drug diffusion coefficients were estimated. No differences in cloud point were observed. The viscosity of the gels strongly depended on HPMC proportions (from 0.7 to 100 mPa.s), which affected to a lesser extent the resistance to the diffusion of the drugs (D values from 60 x 10(-6) to 5 x 10(-6) cm(2)/s). The influence of CD on diffusion was particularly evident in gels prepared with polymer proportions above its entanglement concentration, 2.0% HPMC K4M. In these systems, while high drug/CD proportions enhanced the diffusivity preventing polymer/drug hydrophobic interactions, low drug/CD ratios hindered it. An excess of free CD, especially the bulky HP-beta-CD, made the diffusion of the complexes in the relatively low mesh size 2% polymer network more difficult. In the case of tablets, CD plays an additional role as dissolution rate promoter. To evaluate to what extent the balance between the increase in dissolution rate and the decrease in diffusion rate induced by CD determines drug release, matrix tablets were prepared by direct compression of 100 mg drug and 400 mg polymer/CD/lactose blends, whose composition was chosen following a simplex centroid design. A higher CD/lactose ratio significantly increased the release rate of hydrophobic drugs (sulphamethizole), but decreased the release rate of hydrophilic drugs (diclofenac sodium), indicating the predominance of a different contribution depending on the hydrophilicity of the drug. Therefore, the use of CD derivatives may be particularly useful to modulate drug release from HPMC gels and matrix tablets; the influence of these additives being dependent on the nature of the drug and on the molecular size and hydrophilic character of the CD used.

Cyclodextrins↗

PubMed2004

A comparison of drug loading capacity of cellactose with two ad hoc processed lactose-cellulose direct compression excipients.

This study compares the drug loading capacity of Cellactose and two excipients of similar composition and similar particle size, prepared by dry granulation and extrusion-spheronization respectively. The drugs evaluated were acetaminophen and furosemide. Acetaminophen did not significantly affect the flow properties of any of the excipients, whereas furosemide markedly worsened flow properties, eliminating the differences initially existing among the three excipients. For both drugs, tablet mechanical properties were clearly better with Cellactose than with the other excipients. Acetaminophen dissolution rate was very similar regardless of the excipient used, but furosemide dissolution rate was lower from Cellactose tablets than from tablets prepared with the other excipients. This important difference is discussed in terms of micropore structure, specific surface area, and wettability of tablets, and is attributable to the special structure of Cellactose particles.

Acetaminophen↗

PubMed2003

Controlled release of estradiol solubilized in carbopol/surfactant aggregates.

The potential of carbopol/surfactant dispersions as solubilizing and controlled release systems of estradiol (a poorly water-soluble drug) was evaluated. The solubilization of estradiol in the dispersions of Carbopol 934 (0.25%) and Pluronic F-127, Tween 80, sodium dodecylsulfate (SDS), or benzalkonium chloride (BkCl) was assessed, by differential scanning calorimetry (DSC) of films obtained by desiccation, as a decrease in estradiol melting temperature and enthalpy. The amounts of estradiol solubilized in carbopol/SDS and carbopol/Tween 80 aqueous dispersions were considerably greater (solubilization capacity: 1.3 and 9 times greater) than in the surfactant alone solutions and up to 100 times greater than in water. High aggregates/water equilibrium partition coefficients of estradiol in carbopol/SDS (1768 M(-1)) and carbopol/Tween 80 (14114 M(-1)) dispersions were found. Carbopol/(1%) SDS/(25 mg/dl) estradiol and carbopol/(0.1%) Tween 80/(5 mg/dl) estradiol dispersions had a pH of around 4, were easy flowing, and showed sustained release for at least 1 week. Estradiol diffusion coefficients were greater when the receptor medium was 0.3-1.0% SDS solution than when it was iso-osmotic NaCl solution or pH 7.5 phosphate buffer. At this pH, a viscoelastic gel is formed on the donor side of the membrane and the drug diffusion slowed down. When the receptor medium contains a surfactant, estradiol release seems to happen as a direct exchange between the carbopol/surfactant aggregates and the receptor surfactant micelles. If no surfactant is in the receptor fluid, estradiol/surfactant complexes migrate towards the receptor. Despite the low viscosity of these dispersions, estradiol diffusion coefficients were in the same order of magnitude as those obtained with a commercially available neutralized ethanol/water carbopol gel of estradiol (60 mg/dl). When the receptor medium had no surfactant, the low affinity of estradiol for water prevented drug diffusion from the commercial formulation. In summary, carbopol/surfactant aggregates act as efficient carriers of hydrophobic drugs; the affinity of estradiol for carbopol/surfactant aggregates, their dissociation, and the diffusivity of estradiol/surfactant complexes being key factors in the control of the drug release process.

Acrylic Resins↗

PubMed2003

Cationic cellulose hydrogels: kinetics of the cross-linking process and characterization as pH-/ion-sensitive drug delivery systems.

The cross-linking process of two cationic hydroxyethylcelluloses of different hydroxyethyl and ammonium group contents, polyquaternium-4 (PQ-4) and polyquaternium-10 (PQ-10), with ethylenglycol diglycidylether (EGDE) was characterized and optimized through rheometric analysis of the forming network. The influence of NaOH concentration, temperature, and EGDE concentration on the cross-linking rate were studied. The evolution of the elastic (G') and viscous (G") moduli, recorded in time-sweep experiments carried out at a fixed angular frequency, showed that the cross-linker requires a minimum of 0.05 M NaOH and 30 degrees C to be active. The increase in G' and G" followed first order kinetics, the slopes of G' being higher than those corresponding to G". The gel time, i.e. the time at which the crossover of G' and G" occurs, decreases exponentially when temperature increases from 30 to 60 degrees C. Apparent activation energies, estimated from the gel times, ranged between 70 and 90 kJ/mol. The cross-linking rate was greater in PQ-4 than in PQ-10 owing to the initial lower viscosity and higher content in hydroxyethyl groups of the former. However, IR spectra of the final hydrogels suggest the formation of a similar number of cross-linking junctions in both polymer systems. The optimum conditions for hydrogel preparation were 60 degrees C in 0.10 M NaOH medium, and no depolymerization was observed. Such hydrogels were transparent, presented a smooth, continuous surface, and were superabsorbent in water. After drying in an oven, the degree of swelling was lower than that of freshly prepared hydrogels; the behavior of water uptake being Fickian. The hydrogels presented a significant loading capacity of diclofenac sodium, with which they interact through ionic and hydrophobic bonding. The affinity is kept at an acidic pH, preventing drug release. In contrast, at pH 8 the interactions are broken and the release process is sustained for more than 4 h. The results also indicate that the ionic strength as well as the initial pH of the medium, when the release was evaluated switching the pH from acidic to basic, are two critical factors which have to be considered to extract conclusions about the behavior of the hydrogels as site-specific delivery systems under in vivo conditions.

Cations↗

PubMed2003

Interactions of ibuprofen with cationic polysaccharides in aqueous dispersions and hydrogels. Rheological and diffusional implications.

Non-steroidal antiinflammatory drugs, such as ibuprofen, are amphiphilic substances capable of self-association in aqueous solutions and able to be sorbed onto polymers through hydrophobic and electrostatic bonds. The aim of this work was to analyze the association processes of sodium ibuprofen with cationic celluloses (Celquat H-100 (PQ-4) and SC-230 M (PQ-10)) and cationic guar gums (Ecopol 261-S and 14-S) and their repercussions on the properties of the aqueous dispersions and cross-linked hydrogels. The interaction process was studied in aqueous dispersions through transmittance, surface tension, fluorescence, conductivity, viscosity and oscillatory rheometry measurements. Below cmc, the drug molecules weakly interact with the polymers through hydrophobic and ionic interactions. Around the cmc (4%), a notable decrease in the viscosity, and storage and loss moduli of the dispersions (even precipitation in PQ-10 systems) was observed. An additional increase in drug concentration induced the dispersions to recover their initial properties. Since ibuprofen/polymer cationic groups ratio were in all cases above 1, these observations indicate that drug self-association induces the polymer to coil around the micelles and, as the number of micelles increases (more drug concentration) the polymer chains interact with more of them, uncoiling again to some extent. Polymer (1%) dispersions containing 6% ibuprofen showed drug diffusion coefficients much lower than in water. When a surfactant, sodium dodecylsulfate, was added to these systems the diffusion coefficients decreased even more, suggesting the formation of new associative structures. Chemically cross-linked hydrogels made of these cationic polysaccharides absorb considerable amounts of ibuprofen (up to 15 g/g) and showed a pH-dependent release process. At acidic pH, drug-polymer affinity is maintained, preventing drug release. In contrast, at pH 8 the interactions are broken and the release process is sustained for more than 4h. In summary, ibuprofen interactions with cationic polysaccharides strongly determine the performance of their aqueous dispersions and hydrogels.

Carbohydrate Sequence↗