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Eudragit® L100-55 interpolyelectrolyte complexes using swellability measurements
Abstracts
Conclusions The investigated IPEC is stable and has universal kinetics of swelling and the same swellability both in acidic and in neutral media during 24 h under simulated GIT conditions. The formulated IPEC has transport characteristics that may be used in controlled drug delivery systems. References [1] Moustafine, R.I., Kabanova, T.V., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100, J.Control. Release 103 (2005) 191–198. [2] Moustafine, R.I., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with sodium alginate, Int. J.Pharm. 294 (2005) 113–120. [3] Zhdanova, E.R., Kabanova, T.V., Chisameeva, G.G., Moustafine, R.I., Investigation of interpolymer complexation between Eudragit® E100 and Carbomer 940, 5th World Meeting on Pharm. Biopharm. and Pharm. Technol., Geneva, Switzerland, 2006, accepted for publication. doi:10.1016/j.jconrel.2006.09.035
019 Design of new polymer carriers based of Eudragit® E PO/Eudragit® L100-55 interpolyelectrolyte complexes using swellability measurements R.I. Moustafine, O.V. Bobyleva Department of Pharmaceutical Chemistry, State Medical University of Kazan, Butlerov str., 49, 420012 Kazan, Tatarstan, Russian Federation Abstract Properties of matrices prepared from IPEC's Eudragit® E PO/Eudragit® L100-55 of different composition were investigated using swellability testing. The interpolyelectrolyte complexes showed different swelling characteristics during 6 h in conditions of simulated intestinal tract (SIT) depending upon the composition of the polycomplexes. Compositions of IPEC with Z = 0.86–1.81 could be suitable for colon-specific drug delivery. Introduction Interpolyelectrolyte complexes (IPECs) are a new class of polymer carriers, which play an important role in creating new oral drug delivery systems (DDS). The copolymers most widely used for controlled drug delivery are the different
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types of Eudragit®, which are produced by Röhm GmbH and Co. KG. Systematic investigation of Eudragit® as IPECs in order to modify their structure was done by our group [1–3]. It is well known, that the swelling characteristics of the polymers are to a certain extent predictive for their release properties. The objective of this study was to investigate the swelling properties of some new IPEC compositions prepared from Eudragit® type E PO (EE) and Eudragit® L100-55 (EL) to evaluate their potential application as oral DDS. Gastric soluble EE was selected as the polycationic polymer. On the other hand, EL, which is usually used for enteric coating, was used as the anionic polymer. Experimental methods Synthesis of solid IPEC EE solutions (5 mM, pH 5.2, 5.5, 6.0, 6.5 and 7.0) were mixed with EL solutions of the same pH values (5 mM, pH 5.2, 5.5, 6.0, 6.5 and 7.0) at constant temperature. After isolation of the precipitate from the solution, it was washed with demineralized water and the solid IPEC was dried under vacuum for 2 days at 40 °C. The composition of the formed IPEC (Z) was investigated by elemental analysis using a model CHN-3 elementary analyzer (Dzerginsk, Russia) and as the ratio Z = [EE]/[EL] was calculated. Each material was sieved and the sieve fraction of 0.25 mm was selected. In order to determine the degree of swelling, flatfaced tablets of 100 mg weight and 8 mm diameter were prepared by compressing the required amount of IPEC powder at 25 kg/cm2 using a hydraulic press (Rodac, Sittard, The Netherlands). The degree of swelling was investigated under conditions, which simulated the intestinal tract and could be suitable for colon-specific drug delivery [4]: the first 2 h in buffer solution of pH 5.8, the next 2 h in a buffer solution of pH 6.8, and finally 2 h in buffer solution pH 7.4. The compositions of the media used are described in BP 98. 2. The polymeric matrix is placed in a tarred basket (from the dissolution test equipment) and immersed into a thermostated bath (37.0 ± 0.5 °C). The volume of the swelling medium was 40 ml. The degree of swelling was determined after every 15 min: the basket was removed from the medium, accurately dried by filter paper and weighed. The degree of swelling (H, %) was calculated as: H% ¼ ðm2 −m1 =m1 Þ100 in which m1 is the weight of the dry sample and m2 is the weight of the swollen sample. Results and discussion In our previous study, we found that the swelling properties of the EE\EL IPECs, due to their polycomplex structure,
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Abstracts
[3] Moustafine, R.I., Zaharov, I.M., Kemenova, V.A., Physicochemical characterization and drug release properties of Eudragit® E PO/Eudragit® L100-55 interpolyelectrolyte complexes, Eur.J. Pharm. Biopharm., article in press. [4] Lorenzo-Lamoza, M.L., Remuòán-Lopez, C., Vila-Jato, J.L., Alonso, M.J., Design of microencapsulated chitosan microspheres for colonic drug delivery, J.Control.Release 52 (1998) 109–118. doi:10.1016/j.jconrel.2006.09.036 Fig. 1. Degree of swelling of pure EE, EL and IPEC with different compositions (n=3; ±SD).
definitely have other characteristics compared to the individual copolymers under, simulated gastro-intestinal tract conditions [3]. In the present study, the swelling characteristics of IPECs were determined which were synthesized under different pH conditions, in order to form polycomplexes with different compositions: from samples, which have an excess molar amount of polyanion (Z = 0.21–0.68), to samples with near equimolar compositions (Z = 0.91) and to samples, which have molar excess amount of polycation (Z = 1.81) in simulated gastro-intestinal tract conditions. Fig. 1 shows the swelling profiles from the investigated samples. The individual copolymers are clearly not suitable to be used in oral DDS. The samples of IPEC (Z = 0.21–0.36) had a comparatively rapid increase in swelling because of the increase in ionized COO− groups, mostly localized in ‘defect’ parts of the IPEC structure. In the case of IPECs with Z = 0.68– 1.81, having a well equilibrated structure, we see more stable swelling profiles, not so depending on the test medium condition.
020 Swellability testing of chitosan/Eudragit® L100-55 interpolyelectrolyte complexes for colonic drug delivery E.B. Margulis, R.I. Moustafine Department of Pharmaceutical Chemistry, State Medical University of Kazan, Butlerov str., 49, 420012 Kazan, Tatarstan, Russian Federation Summary The potential use of a new chitosan/Eudragit® L100-55 interpolyelectrolyte complex in colon-specific drug delivery systems (DDS) was investigated and compared with the individual polymers using swellability testing. The IPECs showed more stable swellability profiles during 24 h under simulated intestinal tract conditions, indicating their suitability for use in colon-specific drug delivery.
Conclusions Introduction The results indicated that some of the investigated IPECs (Z = 0.86–1.81) have sufficiently stable and robust swelling kinetics with almost identical swellability in acidic and in neutral media during 6 h in simulated gastro-intestinal tract conditions. These IPECs have transport characteristics that may be suitable for colon-specific controlled drug delivery. On the other hand, other IPECs (Z = 0.21–0.36) could be used for controlled release of drugs which are absorbed in the upper parts of the gastro-intestinal tract. References [1] Moustafine, R.I., Kabanova, T.V., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100, J.Control. Release 103 (2005) 191–198. [2] Moustafine, R.I., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with sodium alginate, Int.J.Pharm. 294 (2005) 113–120.
Interpolyelectrolyte complexes (IPECs) as polymeric carriers in controlled drug release systems are already well investigated [1]. IPECs with polysaccharides, obtained as precipitates by mixing cationic and anionic polymers in aqueous solutions, have been reported previously, mostly including chitosan (CS) as polycation. The approach is also used in the preparation of CS multicore microspheres, coated by Eudragit® types S or L. To the best of our knowledge, this is the only scientific report describing the ionic interactions of Eudragit® S with the polysaccharide CS, although the authors studied the interaction only by IR analysis of the pellet film coating during the release measurements. However, the physicochemical characteristics of the system were not investigated [2]. Systematic investigations involving Eudragit® polymers in IPECs were performed by our group [3–5]. The purpose of the present study was to characterize the swellability properties of IPECs prepared from CS and Eudragit® L100-55 (L100-55) in relation to their possible
Conclusions The investigated IPEC is stable and has universal kinetics of swelling and the same swellability both in acidic and in neutral media during 24 h under simulated GIT conditions. The formulated IPEC has transport characteristics that may be used in controlled drug delivery systems. References [1] Moustafine, R.I., Kabanova, T.V., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100, J.Control. Release 103 (2005) 191–198. [2] Moustafine, R.I., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with sodium alginate, Int. J.Pharm. 294 (2005) 113–120. [3] Zhdanova, E.R., Kabanova, T.V., Chisameeva, G.G., Moustafine, R.I., Investigation of interpolymer complexation between Eudragit® E100 and Carbomer 940, 5th World Meeting on Pharm. Biopharm. and Pharm. Technol., Geneva, Switzerland, 2006, accepted for publication. doi:10.1016/j.jconrel.2006.09.035
019 Design of new polymer carriers based of Eudragit® E PO/Eudragit® L100-55 interpolyelectrolyte complexes using swellability measurements R.I. Moustafine, O.V. Bobyleva Department of Pharmaceutical Chemistry, State Medical University of Kazan, Butlerov str., 49, 420012 Kazan, Tatarstan, Russian Federation Abstract Properties of matrices prepared from IPEC's Eudragit® E PO/Eudragit® L100-55 of different composition were investigated using swellability testing. The interpolyelectrolyte complexes showed different swelling characteristics during 6 h in conditions of simulated intestinal tract (SIT) depending upon the composition of the polycomplexes. Compositions of IPEC with Z = 0.86–1.81 could be suitable for colon-specific drug delivery. Introduction Interpolyelectrolyte complexes (IPECs) are a new class of polymer carriers, which play an important role in creating new oral drug delivery systems (DDS). The copolymers most widely used for controlled drug delivery are the different
e35
types of Eudragit®, which are produced by Röhm GmbH and Co. KG. Systematic investigation of Eudragit® as IPECs in order to modify their structure was done by our group [1–3]. It is well known, that the swelling characteristics of the polymers are to a certain extent predictive for their release properties. The objective of this study was to investigate the swelling properties of some new IPEC compositions prepared from Eudragit® type E PO (EE) and Eudragit® L100-55 (EL) to evaluate their potential application as oral DDS. Gastric soluble EE was selected as the polycationic polymer. On the other hand, EL, which is usually used for enteric coating, was used as the anionic polymer. Experimental methods Synthesis of solid IPEC EE solutions (5 mM, pH 5.2, 5.5, 6.0, 6.5 and 7.0) were mixed with EL solutions of the same pH values (5 mM, pH 5.2, 5.5, 6.0, 6.5 and 7.0) at constant temperature. After isolation of the precipitate from the solution, it was washed with demineralized water and the solid IPEC was dried under vacuum for 2 days at 40 °C. The composition of the formed IPEC (Z) was investigated by elemental analysis using a model CHN-3 elementary analyzer (Dzerginsk, Russia) and as the ratio Z = [EE]/[EL] was calculated. Each material was sieved and the sieve fraction of 0.25 mm was selected. In order to determine the degree of swelling, flatfaced tablets of 100 mg weight and 8 mm diameter were prepared by compressing the required amount of IPEC powder at 25 kg/cm2 using a hydraulic press (Rodac, Sittard, The Netherlands). The degree of swelling was investigated under conditions, which simulated the intestinal tract and could be suitable for colon-specific drug delivery [4]: the first 2 h in buffer solution of pH 5.8, the next 2 h in a buffer solution of pH 6.8, and finally 2 h in buffer solution pH 7.4. The compositions of the media used are described in BP 98. 2. The polymeric matrix is placed in a tarred basket (from the dissolution test equipment) and immersed into a thermostated bath (37.0 ± 0.5 °C). The volume of the swelling medium was 40 ml. The degree of swelling was determined after every 15 min: the basket was removed from the medium, accurately dried by filter paper and weighed. The degree of swelling (H, %) was calculated as: H% ¼ ðm2 −m1 =m1 Þ100 in which m1 is the weight of the dry sample and m2 is the weight of the swollen sample. Results and discussion In our previous study, we found that the swelling properties of the EE\EL IPECs, due to their polycomplex structure,
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Abstracts
[3] Moustafine, R.I., Zaharov, I.M., Kemenova, V.A., Physicochemical characterization and drug release properties of Eudragit® E PO/Eudragit® L100-55 interpolyelectrolyte complexes, Eur.J. Pharm. Biopharm., article in press. [4] Lorenzo-Lamoza, M.L., Remuòán-Lopez, C., Vila-Jato, J.L., Alonso, M.J., Design of microencapsulated chitosan microspheres for colonic drug delivery, J.Control.Release 52 (1998) 109–118. doi:10.1016/j.jconrel.2006.09.036 Fig. 1. Degree of swelling of pure EE, EL and IPEC with different compositions (n=3; ±SD).
definitely have other characteristics compared to the individual copolymers under, simulated gastro-intestinal tract conditions [3]. In the present study, the swelling characteristics of IPECs were determined which were synthesized under different pH conditions, in order to form polycomplexes with different compositions: from samples, which have an excess molar amount of polyanion (Z = 0.21–0.68), to samples with near equimolar compositions (Z = 0.91) and to samples, which have molar excess amount of polycation (Z = 1.81) in simulated gastro-intestinal tract conditions. Fig. 1 shows the swelling profiles from the investigated samples. The individual copolymers are clearly not suitable to be used in oral DDS. The samples of IPEC (Z = 0.21–0.36) had a comparatively rapid increase in swelling because of the increase in ionized COO− groups, mostly localized in ‘defect’ parts of the IPEC structure. In the case of IPECs with Z = 0.68– 1.81, having a well equilibrated structure, we see more stable swelling profiles, not so depending on the test medium condition.
020 Swellability testing of chitosan/Eudragit® L100-55 interpolyelectrolyte complexes for colonic drug delivery E.B. Margulis, R.I. Moustafine Department of Pharmaceutical Chemistry, State Medical University of Kazan, Butlerov str., 49, 420012 Kazan, Tatarstan, Russian Federation Summary The potential use of a new chitosan/Eudragit® L100-55 interpolyelectrolyte complex in colon-specific drug delivery systems (DDS) was investigated and compared with the individual polymers using swellability testing. The IPECs showed more stable swellability profiles during 24 h under simulated intestinal tract conditions, indicating their suitability for use in colon-specific drug delivery.
Conclusions Introduction The results indicated that some of the investigated IPECs (Z = 0.86–1.81) have sufficiently stable and robust swelling kinetics with almost identical swellability in acidic and in neutral media during 6 h in simulated gastro-intestinal tract conditions. These IPECs have transport characteristics that may be suitable for colon-specific controlled drug delivery. On the other hand, other IPECs (Z = 0.21–0.36) could be used for controlled release of drugs which are absorbed in the upper parts of the gastro-intestinal tract. References [1] Moustafine, R.I., Kabanova, T.V., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with Eudragit L100, J.Control. Release 103 (2005) 191–198. [2] Moustafine, R.I., Kemenova, V.A., Mooter, van den G., Characteristics of interpolyelectrolyte complexes of Eudragit E100 with sodium alginate, Int.J.Pharm. 294 (2005) 113–120.
Interpolyelectrolyte complexes (IPECs) as polymeric carriers in controlled drug release systems are already well investigated [1]. IPECs with polysaccharides, obtained as precipitates by mixing cationic and anionic polymers in aqueous solutions, have been reported previously, mostly including chitosan (CS) as polycation. The approach is also used in the preparation of CS multicore microspheres, coated by Eudragit® types S or L. To the best of our knowledge, this is the only scientific report describing the ionic interactions of Eudragit® S with the polysaccharide CS, although the authors studied the interaction only by IR analysis of the pellet film coating during the release measurements. However, the physicochemical characteristics of the system were not investigated [2]. Systematic investigations involving Eudragit® polymers in IPECs were performed by our group [3–5]. The purpose of the present study was to characterize the swellability properties of IPECs prepared from CS and Eudragit® L100-55 (L100-55) in relation to their possible