Interpolymer Complexes Based on Eudragit® EPO/Eudragit® S100 as Carriers for Oral Controlled Drug Delivery Systems
https://doi.org/10.33380/2305-2066-2020-9-3-36-43
Abstract
Introduction. The possibility of obtaining IPC based on polyanions of various structures Eudragit®, Carbopol®, pectin, carrageenan and sodium alginate with oppositely charged polycations - Eudragit® EPO, Eudragit® RS/RL and chitosan, stabilized as already well-known by ionic bonds. It has been proven that interpolymer complexes with the participation of Eudragit® copolymers could be also formatted by hydrogen bonds too as well. Prepared polycomplexes are promising carriers for drug delivery systems (DDS) to various parts of the gastrointestinal tract (GIT): the mouth (orodispersible and buccal DDS), stomach (gastroretentive DDS) and intestine (colon-specific DDS).
Aim. Study of interpolymer complexes based on a pair of Eudragit® EPO and Eudragit® S100 copolymers obtained in a medium of various organic solvents (ethyl alcohol and a mixture of isopropanol-acetone (in a ratio of 60:40, v/v) from the point of view of their use in oral matrix systems for the delivery of active pharmaceutical ingredients.
Materials and methods. The synthesis of interpolymer complexes based on Eudragit® copolymers was carried out in organic solvents [ethyl alcohol or isopropanol-acetone mixture (in a ratio of 60:40, v/v)]. The structural features of the obtained IPCs were assessed by FTIR spectroscopy using a Nicolet iS5 instrument with a Smart iTR single ATR attachment (Thermo Scientific, USA) and differential scanning calorimetry with modulated temperature (mDSC) using a Discovery™ DSC instrument (TA Instruments, USA). The composition was determined using the method of elemental analysis on a Thermo Flash 2000 CHNS/O device (Thermo Fisher Scientific, UK). The swelling capacity of the obtained IPCs was evaluated in buffer media with pH values that mimic the pH of different parts of the gastrointestinal tract (GIT): 1.2; 5.8; 6.8 and 7.4. The release of theophylline (TEO) and diclofenac sodium (DS) was assessed on a ERWEKA DFZ II (ERWEKA GmbH, Germany) flow through cell apparatus in buffer media simulating the pH of various parts of the gastrointestinal tract for 7 hours.
Results and discussion. All obtained IPCs are characterized by an excess of Eudragit® S100 in their composition. The obtained IPCs are stabilized by a cooperative system of ionic and hydrogen bonds. DSC thermograms of IPC samples are characterized by the presence of a single glass transition temperature, which confirms the absence of impurities of free copolymers in their composition, while with an increase in the content of Eudragit® S100 in the IPC composition, the glass transition temperature increases. The matrix based on IPC-1 disintegrated during the first 15 minutes of the experiment in a medium with pH 1.2, while matrices based on the rest of the IPC samples retain their shape for 7 hours and are characterized by pH-independent behavior. The release of TEO from polycomplex matrices is diffusion-controlled and occurs in accordance with Fick's law (IPC-2, IPC-4, and IPC-6) or can be characterized as «abnormal transport» (IPC-1, IPC-3 and IPC- 5), and also depends on the swelling capacity of the matrix. In contrast, the release of DS is dependent on surface erosion of the matrix, which is consistent with the Super Case II transport mechanism.
Conclusion. The resulting interpolymer complexes Eudragit® EPO/Eudragit® S100 are promising carriers in matrix oral systems for the controlled delivery of active pharmaceutical ingredients, providing a prolonged release of BCS class I substances, depending on the diffusion rate from the swollen matrix, and a delayed release of BCS class II substances, controlled by surface processes erosion of the matrix.
Aim. Study of interpolymer complexes based on a pair of Eudragit® EPO and Eudragit® S100 copolymers obtained in a medium of various organic solvents (ethyl alcohol and a mixture of isopropanol-acetone (in a ratio of 60:40, v/v) from the point of view of their use in oral matrix systems for the delivery of active pharmaceutical ingredients.
Materials and methods. The synthesis of interpolymer complexes based on Eudragit® copolymers was carried out in organic solvents [ethyl alcohol or isopropanol-acetone mixture (in a ratio of 60:40, v/v)]. The structural features of the obtained IPCs were assessed by FTIR spectroscopy using a Nicolet iS5 instrument with a Smart iTR single ATR attachment (Thermo Scientific, USA) and differential scanning calorimetry with modulated temperature (mDSC) using a Discovery™ DSC instrument (TA Instruments, USA). The composition was determined using the method of elemental analysis on a Thermo Flash 2000 CHNS/O device (Thermo Fisher Scientific, UK). The swelling capacity of the obtained IPCs was evaluated in buffer media with pH values that mimic the pH of different parts of the gastrointestinal tract (GIT): 1.2; 5.8; 6.8 and 7.4. The release of theophylline (TEO) and diclofenac sodium (DS) was assessed on a ERWEKA DFZ II (ERWEKA GmbH, Germany) flow through cell apparatus in buffer media simulating the pH of various parts of the gastrointestinal tract for 7 hours.
Results and discussion. All obtained IPCs are characterized by an excess of Eudragit® S100 in their composition. The obtained IPCs are stabilized by a cooperative system of ionic and hydrogen bonds. DSC thermograms of IPC samples are characterized by the presence of a single glass transition temperature, which confirms the absence of impurities of free copolymers in their composition, while with an increase in the content of Eudragit® S100 in the IPC composition, the glass transition temperature increases. The matrix based on IPC-1 disintegrated during the first 15 minutes of the experiment in a medium with pH 1.2, while matrices based on the rest of the IPC samples retain their shape for 7 hours and are characterized by pH-independent behavior. The release of TEO from polycomplex matrices is diffusion-controlled and occurs in accordance with Fick's law (IPC-2, IPC-4, and IPC-6) or can be characterized as «abnormal transport» (IPC-1, IPC-3 and IPC- 5), and also depends on the swelling capacity of the matrix. In contrast, the release of DS is dependent on surface erosion of the matrix, which is consistent with the Super Case II transport mechanism.
Conclusion. The resulting interpolymer complexes Eudragit® EPO/Eudragit® S100 are promising carriers in matrix oral systems for the controlled delivery of active pharmaceutical ingredients, providing a prolonged release of BCS class I substances, depending on the diffusion rate from the swollen matrix, and a delayed release of BCS class II substances, controlled by surface processes erosion of the matrix.
Keywords
interpolymer complexes,
Eudragit®,
diclofenac sodium,
theophylline,
oral delivery,
controlled drug delivery
Supporting agencies: This work was financially supported by the Russian Science Foundation (RSF) in the framework of research project № 20-65-46007 (to A.V.B. and R.I.M.). The authors are also grateful to ERWEKA GmbH for the opportunity to work on the Flow Trough Cell Apparatus DFZ II, and also to Evonik Rohm GmbH for providing samples of Eudragit® copolymers.
About the Authors
A. V. Bukhovets
Institute of Pharmacy, Kazan State Medical University
Russian Federation
Russian Federation
Aleksandra V. Bukhovets.
16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126.
A. Y. Sitenkov
Institute of Pharmacy, Kazan State Medical University
Russian Federation
Russian Federation
Alexander Y. Sitenkov.
16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126.
R. I. Moustafine
Institute of Pharmacy, Kazan State Medical University
Russian Federation
Russian Federation
Rouslan I. Moustafine.
16, Fatykha Amirkhan str., Kazan, Republic of Tatarstan, 420126.
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Review
For citations:
Bukhovets A.V., Sitenkov A.Y., Moustafine R.I. Interpolymer Complexes Based on Eudragit® EPO/Eudragit® S100 as Carriers for Oral Controlled Drug Delivery Systems. Drug development & registration. 2020;9(3):36-43. (In Russ.) https://doi.org/10.33380/2305-2066-2020-9-3-36-43
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