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

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

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

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

Hybrid Nanoparticles for Haloperidol Encapsulation: Quid Est Optimum?

The choice of drug delivery carrier is of paramount importance for the fate of a drug in a human body. In this study, we have prepared the hybrid nanoparticles composed of FDA-approved Eudragit L100-55 copolymer and polymeric surfactant Brij98 to load haloperidol-an antipsychotic hydrophobic drug used to treat schizophrenia and many other disorders. This platform shows good drug-loading efficiency and stability in comparison to the widely applied platforms of mesoporous silica (MSN) and a metal-organic framework (MOF). ZIF8, a biocompatible MOF, failed to encapsulate haloperidol, whereas MSN only showed limited encapsulation ability. Isothermal titration calorimetry showed that haloperidol has low binding with the surface of ZIF8 and MSN in comparison to Eudragit L100-55/Brij98, thus elucidating the striking difference in haloperidol loading. With further optimization, the haloperidol loading efficiency could reach up to 40% in the hybrid Eudragit L100-55/Brij98 nanoparticles with high stability over several months. Differential scanning calorimetry studies indicate that the encapsulated haloperidol stays in an amorphous state inside the Eudragit L100-55/Brij98 nanoparticles. Using a catalepsy and open field animal tests, we proved the prolongation of haloperidol release in vivo, resulting in later onset of action compared to the free drug

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

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

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

THE FEATURES OF THE PREDICTIVE DISSOLUTION TESTING (REVIEW)

Dissolution test plays an important role at different levels of the development and manufacturing drugs as one of the major quality control tools and an integral part of In vitro tests in the study of drug release from the developed dosage forms. Article describes the basic parameters that should be considered in predictive dissolution tests, such as the selection criteria and the composition of biorelevant dissolution media, fluid dynamics, volume and transfer of the dissolution media