Physicochemical characterization and drug release properties of Eudragit® E PO/Eudragit® L 100-55 interpolyelectrolyte complexes

The formation of interpolyelectrolyte complexes (IPEC) between Eudragit® E PO (EE) and Eudragit® L 100-55 (EL) was investigated, using turbidimetry, apparent viscosity measurements, elementary analysis and MT-DSC. The structure of the synthesized IPEC was investigated using FT-IR spectroscopy. The binding ratio of a unit molecule of EL with EE was found to be approximately 1:1 at pH 5.5. Based on the results of elementary analysis and FT-IR, the binding ratio of each component in the solid complexes was very close to that observed in turbidity and apparent viscosity measurements and indicate that the synthesized products can be considered as IPEC. As a result of electrostatic interaction between the polymer chains, the glass transition temperature of the IPEC increased significantly. Due to the structure of the IPEC, two maxima were observed in the swelling behavior as a function of pH. The release of the model drug ibuprofen (IBF) was significantly retarded from tablets made up of the IPEC as compared with individual copolymers, its physical mixture and Eudragit® RL PO (RL), RS PO (RS). © 2005 Elsevier B.V. All rights reserved

Characteristics of interpolyelectrolyte complexes of Eudragit E 100 with sodium alginate

With a view to the application in oral drug delivery formulations, the possibility to form interpolyelectrolyte complexes (IPEC) of Eudragit E 100 (EE) with sodium alginate (AL) was investigated, employing turbidimetry, apparent viscosity measurements, FT-IR and elementary analysis. The interaction or binding ratio of a unit molecule of AL with EE was largely affected by the pH value of the media, showing a change from 1.5:1 to 1:1.25 (0.66 < Z < 1.25) with increase in pH value from 2.5 to 6.0. Based on the results of elementary analysis and FT-IR, the interaction ratio of each component in the solid complexes was very close to that observed in turbidity and apparent viscosity measurements thus proving that the synthesized products actually can be considered as IPEC. © 2005 Elsevier B.V. All rights reserved

А study of haloperidol release from polycomplex nanoparticles based on Eudragit® copolymers

Introduction. The development of polymer carriers for micro- and nanoscale drug delivery systems is an emerging area of modern pharmaceutical technology. One of the urgent needs in this area is the development of effective methods to study the drug release from these systems. Aim. This work aimed to study the release of a model drug (MD) haloperidol from polycomplex nanoparticles prepared based on interpolyelectrolyte complexes (IPEC) using various methods. Materials and methods. IPECs were prepared in the form of nanoparticles based on pharmaceutical polymers (Eudragit® EPO and Eudragit® L100-55). Size distribution of these nanoparticles were determined using dynamic light scattering on Zetasizer Nano-ZS equipment (Malvern Instruments, UK). The release of haloperidol was studied in a medium simulating an artificial nasal fluid using a vertical Franz diffusion cell (PermeGear, USA) as well as a modified USP IV method in a flow-through cell apparatus (DFZ II, Erweka, Germany). Results and discussion. Statistically significant increase in the release of haloperidol from polycomplex nanoparticles in contrast with the control (haloperidol solution) is observed when using a vertical diffusion or Franz cell, after almost 2.5 hours. At the same time, it was not possible to study the release of drug using the flow-through cell method (USP IV), due, apparently, to the effect of crystallization of haloperidol on the surface of dialysis membranes in the Float-A-Lyzer® G2 nanoadapters. The attempts to eliminate this effect and to improve the membrane permeability to haloperidol by adding surfactants (tween-80) and penetration enhancers (DMSO) were not successful. Conclusion. Both methods are promising for studying the release of drugs from nanosized carriers; however, in the case of using poorly-soluble drugs, including haloperidol, the diffusion method using a vertical Franz cell is effective

Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100

With a view to the application in oral controlled drug delivery systems, the formation of interpolyelectrolyte complexes (IPEC) between Eudragit E100 (EE) and Eudragit L100 (EL) was investigated, using turbidimetry, solution viscosity measurements and elementary analysis. The structure of the synthesized IPEC was investigated by using FT-IR spectroscopy. The binding ratio of a unit molecule of EL with EE was found to be approximately 1:1 in pH 6.0. Based on the results of elementary analysis, and FT-IR, the binding ratio of each component in the solid complexes was very close to that observed in turbidity and viscosity measurements and indicate that the synthesized products can be considered as IPEC. Due to the structure of the IPEC, two maxima were observed in the swelling behaviour as a function of pH. The release of the model drug ibuprofen was significantly retarded from tablets made up of the IPEC. © 2004 Elsevier B.V. All rights reserved

Comparative evaluation of interpolyelectrolyte complexes of chitosan with Eudragit® L100 and Eudragit® L100-55 as potential carriers for oral controlled drug delivery

With a view to the application in oral controlled drug delivery systems, the formation of interpolyelectrolyte complexes (IPEC) between chitosan (CS) and Eudragit® L100 (L100) or Eudragit® L100-55 (L100-55) was investigated at pH 6.0, using elementary analysis. The interaction or binding ratio of a unit molecule of CS with Eudragit® L copolymers depends on the molecular weight of CS, and changes from 1:0.85 to 1:1.22 (1.17 < φ < 0.82) for L100 and from 1:1.69 to 1:1.26 (0.60 < φ < 0.79) for L100-55, respectively. Based on the results of FT-IR, the structure of the IPECs can change substantially as a function of pH (from 5.8 till 7.4). Swelling behavior of physical mixtures (PM) is definitely different, and potential interactions between the two polyelectrolytes were not observed. The release of the model drug diclofenac sodium (DS) was significantly delayed from tablets made up of the IPEC and can be modified by two ways: choosing Eudragit® L copolymer types and/or changing the molecular weight of CS in the IPECs composition. © 2008 Elsevier B.V. All rights reserved

Drug release modification by interpolymer interaction between countercharged types of Eudragit® RL 30D and FS 30D in double-layer films

Interpolymer interactions between the countercharged methacrylate copolymers Eudragit® RL 30D (polycation) and Eudragit® FS 30D (polyanion), were investigated in conditions mimicking the gastrointestinal environment. The formation of inter-macromolecular ionic bonds between Eudragit® RL 30D and Eudragit® FS 30D was investigated using FT-IR spectroscopy and modulated DSC. The FT-IR spectra of the tested polymeric matrices are characterized by visible changes in the observed IR region indicating the interaction between chains of two oppositely charged copolymers. A new band at 1570 cm-1 appeared which was assigned to the absorption of the carboxylate groups that form the ionic bonds with the quaternary ammonium groups. Moreover, while increasing the pH values from pH 5.8 to 7.4, a decrease of the intensity of the band at 960 cm-1 (quaternary ammonium group vibration) was observed. All binary mixtures were characterized by the presence of only one and narrow Tg, pointing to sample homogeneity, because of the compatibility of components. As a result of electrostatic interaction between the copolymer chains during swelling, the resulting Tg is decreased significantly and was dependent on the quantity of copolymers present in the structure of polycomplexes formed. Overall, the interaction between countercharged copolymers during passage in gastrointestinal tract can strongly modify the release profile of the model drug diclofenac sodium. © 2012 Elsevier B.V. All rights reserved

Interpolyelectrolyte complexes of Eudragit® e PO with sodium alginate as potential carriers for colonic drug delivery: Monitoring of structural transformation and composition changes during swellability and release evaluating

Background: With a view to the application in oral colon drug delivery systems, swelling and release behavior of synthesized interpolyelectrolyte complexes (IPEC) between sodium alginate and Eudragit® EPO were investigated. Method: The microenvironmental changes in IPECs structure as a function of pH during swellability testing were investigated using FT-IR spectroscopy and elementary analysis. Results: All samples of IPECs (Z 0.661.25) during swelling were transformed to a similar structure with approximately the same composition. The release of the model drug diclofenac sodium was significantly delayed from matrices made up of the IPECs and independent from the composition of polycomplexes. Conclusion: According to the obtained results, these IPECs can be considered to have potential in colonic drug delivery as combined pH- and time-dependent systems. © 2009 Informa UK, Ltd

Interpolymer complexes based on Carbopol^® and poly(2-ethyl-2-oxazoline) as carriers for buccal delivery of metformin

Introduction. Buccal drug delivery has a number of advantages over oral administration: ease of application, good blood supply to the buccal mucosa, drug can enter the systemic circulation directly, avoiding the "first pass effect through the liver", and are not exposed to the acidic environment of the gastric juice and the destructive action of digestive enzymes. The use of interpolymer complexes (IPCs) makes it possible not only to ensure adhesion to the mucosal membranes of the oral cavity, but also to achieve a prolonged release of drugs.Aim. Development of carriers based on interpolymer complexes using Carbopol® 971 NF (C971) and poly(2-ethyl-2-oxazoline) (POZ) of different molecular weights for buccal delivery of metformin (MF).Materials and methods. The study of IPC adhesion was carried out using a TA.XTplus texture analyzer (Stable Micro Systems, UK); mucin compacts with a diameter of 13 mm were used as a substrate; these were prepared by compressing porcine gastric mucin powder using a manual hydraulic press for IR spectroscopy (PerkinElmer, USA) at a pressure of 2.45 MPa. The study of the swelling capacity was carried out by placing polymer matrices in an artificial saliva medium, with constant thermostating at a temperature of 37.0 ± 0.5 °C for 5 hours. The study of the release of MF from the matrices based on IPC was carried out using a DFZ II apparatus (Erweka, Germany) according to the Flow Through Cell method (USP IV) with cells for tablets (22.6 mm) and adaptors for ointments, creams and gels in a medium simulating saliva. The concentration of MF in the samples from the dissolution tests was determined with UV-spectrophotometry (Lambda, PerkinElmer, USA) at 232.8 nm.Results and discussion. In a comparative study of the mucoadhesive properties of polymer samples, IPC compacts showed a mucoadhesion capacity comparable to that of poly(2-ethyl-2-oxazoline); at the same time, compacts from physical mixtures (PM) and C971 are inferior in terms of the separation force to IPC samples, however, POZes dissolve in an artificial saliva medium, that is, they are not suitable as dosage forms for buccal delivery. For 5 hours of the experiment to assess the swelling capacity, the IPC matrices did not change significantly, which can ensure their comfortable use as carriers for buccal delivery. When evaluating the release of metformin from polymer matrices (with weight ratio MF/IPC 1: 0.5), the most complete release (more than 90 %) is observed from both IPC matrices compared to matrices of PM and individual polymers.Conclusion. Polycomplex matrix systems based on C971-POZ (50 kDa) and C971-POZ (500 kDa) are suitable for buccal delivery of metformin

Structural transformations during swelling of polycomplex matrices based on countercharged (meth)acrylate copolymers (Eudragit® EPO/Eudragit® L 100-55)

With a view to the application in oral controlled drug delivery systems (DDS), the design of new interpolyelectrolyte complexes (IPECs) between countercharged types of Eudragit® EPO (EPO) and Eudragit® L 100-55 (L100-55) was investigated. The formation and composition of four new IPECs between EPO and L100-55 were established by elementary analysis. The structure of the synthesized IPEC was investigated using FTIR spectroscopy and modulated-temperature differential scanning calorimetry. The binding ratio of a unit molecule of EPO with L100-55 was found to range between 1:2.75 (Z = 0.36) and 1:0.55 (Z = 1.81) while increasing the pH value from 5.5 to 7.0. As a result of electrostatic interaction between the copolymer chains, the glass transition temperature of the IPEC increased significantly. A large pH-sensitive swelling behavior was observed for different structures of the IPECs. The outcome of swelling and diclofenac sodium release from the polycomplex matrices confirm that they have great potential to be used as a controlled DDS in specified regions of gastrointestinal tract. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Cataleptogenic effect of haloperidol formulated in water-soluble calixarene-based nanoparticles

In this study, a water-soluble form of haloperidol was obtained by coaggregation with calix[4]resorcinol bearing viologen groups on the upper rim and decyl chains on the lower rim to form vesicular nanoparticles. The formation of nanoparticles is achieved by the spontaneous loading of haloperidol into the hydrophobic domains of aggregates based on this macrocycle. The mucoadhesive and thermosensitive properties of calix[4]resorcinol–haloperidol nanoparticles were established by UV-, fluorescence and CD spectroscopy data. Pharmacological studies have revealed low in vivo toxicity of pure calix[4]resorcinol (LD50 is 540 ± 75 mg/kg for mice and 510 ± 63 mg/kg for rats) and the absence of its effect on the motor activity and psycho-emotional state of mice, which opens up a possibility for its use in the design of effective drug delivery systems. Haloperidol formulated with calix[4]resorcinol exhibits a cataleptogenic effect in rats both when administered intranasally and intraperitoneally. The effect of the intranasal administration of haloperidol with macrocycle in the first 120 min is comparable to the effect of commercial haloperidol, but the duration of catalepsy was shorter by 2.9 and 2.3 times (p < 0.05) at 180 and 240 min, respectively, than that of the control. There was a statistically significant reduction in the cataleptogenic activity at 10 and 30 min after the intraperitoneal injection of haloperidol with calix[4]resorcinol, then there was an increase in the activity by 1.8 times (p < 0.05) at 60 min, and after 120, 180 and 240 min the effect of this haloperidol formulation was at the level of the control sample