- Email: [email protected]
Viscosity of niosome dispersions
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INVESTIGATIONS ON TOPICAL FORMULATIONS OF CLOMIPAENE CITRATE FOR TREATMENT OF HPV LESIONS E Cevher, N. 0. Sahin,A.Araman Istanbul University, Faculty of Pharmacy, Department of Phannaceutlcal Technology, Beyazit 34452, Istanbul-TURKEY Cluman Papilloma Vuus (HPV) infections are commonly seen in women and cause displastic lesions in genital region. The convwional therapy mcludes caterizatmn, cryosurgery, laser techmques and chemotherapy. rlnterferrm a-2a, podophylii, and cytostatic drugs are used in chemotherapy with limited success. Clomiphene citrate (CC), a nonsterad estrogen analogue with antiestrogen actiwty, 1s commonly used per oral m treatment of infettility in women. H.J Schti et al. prepared an ointment and a cream containing CC and applied these formulatrons to the patim with HPV topically. The therapeutic response was satisfying. Based on these data, we set the goal of our study fo develop a new topical formulation of CC for treatment of HPV displastic lesions. Bioadhesive gels with controlled release characteristics were prepared using poly(acrylic acid) derivatives. The greatest advantages of such gels are to provide controlled release of CC and to maintam the drug in the vagina for extended period of time. This reduces dosing 6equency and thus, improves patient compliance. In vitro release characteristics of CC from different formulations were investigated and compared to those of conventional creams and ointments pH of gels were measured right a&r preparation and 1 month later Shearing stickness of gels were measured using a modified adheswes tester at 2WC. In vitro release rates were determined over a predetermined time period (24 h) using the modified apparatus for disintegration of vaginal tablets described in BP at 37+2’C. Tbe favorable drug release characteristics in vitro suggest that tbrther in viva investigation of this drug delivery system in treatment of HPV lesions is warranted.
OPTIMIZED PREPARATION OF POLY(LACTIDE-CO-CLYCOLIDE)POLY(ETHYLENECLYCOL) NANOPARTICLES LOADED WITH CISPLATIN A. Beletsi(l), P. Klepetsanis(l), D.S. Ithakissios(l), S. Kounias(2), A. Stavropoulos(2) and K.Aveoustakis( 11 (I) University of Patras. Lab. of Pharmaceutical Technology, Patras 261 IO, Greece. (2) University of Athens, Dept. of Mathematics, Panepistemiopolis 15784, Athens, Greece. A central composite experimental design was applied to investigate the effect of five preparative variables on the size and drug loading of PLGA-PEG-cisplatin nanoparticles. The nanoparticles were prepared by transferring an acetone-dimethylformamide solution of polymer and drug in a stirred aqueous buffer pH 7.4 containing sodium cholate as emulsifier. The organic phase was evaporated under controlled temperature and the size and drug content of the resulting nanoparticles were determined using photon correlation spectroscopy and atomic absorption spectroscopy respectively. The preparative variables investigated were: solids concentration, aqueous to organic phase volume ratio, temperature, rate o!’organic phase addition in aqueous phase, and agitation. The size and the drug loading of the prepared nanoparticles ranged between 90-l 80 nm and O-40% respectively. The fitted model could adequately describe the experimental data. The statistical analysis showed that all preparative variables studied, except temperature, affected significantly both the size and the drug loading of nanoparticles. The size was most affected by agitation whereas the loading was Imost affected by the phase ratio. Significant interactions between the preparative variables were also observed. The desirability function approach (Derringer and Suich, J. Qual. Technol.,l2( 1980)214-2 19) was applied to determine the optimum conditions for the preparation of the PLGA-PEG-cisplatin nanoparticles.
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WSCOSITY OF NIOSOME DISPERSIONS P. Anmothavanun. S. Kiri, A. T. Florence Centre.for Dmg Delivery Research,The School of Pharmacy, Universityof London, 29-39 Brunswick Square. London WClN lAX, UK
NEW CONTROL SYSTEM FOR THE DETECTION RESIDUES IN FOODS: MATRIX TABLETS*
Niosomes are colloidal dispersions formed by self-assembly of nonionic surfactants. Their capability to entrap solutes allows them to be used as drug carriers.‘~* Little has been published on the rheological characteristics of these dispersions or of their phospholipid counterparts. We have shown that the viscosity of niosomes is affecled by temperature and shape of the vesicles. Further studies have been performed to investigate other factors which affect their rheology. Vesicles formed mainly by Span 60 (sorbitan monostearate) and cholesterol were used as models; with an addition of a hydrophilic surfactant, Solulan C24 (poly 24 oxyethylene cholesteryl ether); or a charged surfactant, dicetyl phosphate (DCP). The relative viscosity of the dilute vesicle dispersions was measured against water using a suspended level dilution viscometer. The viscosity of the dispersions increases on increasing the vesicle concentration or reducing the vesicle size. Increasing the amount of Solulan C24 in the vesicle membranes results in higher viscosity due to the increased hydration. The presence of NaCl in the medium reduces the viscosity of DCPcontaining vesicles as the electric diffuse layers are suppressed. The factors affecting the viscosity of these dispersions are complex. Intqretation of intrinsic viscosity values is complicated by the lamellarity and perhaps flexibility of some vesicle formulations in flow, but an attempt has nevertheless heen made to estimate hydration from the data. Acknowledgements: P.A. was supported by the Government Phamweutical Organisation. Thailand. References: I. Florence, A.T. (1993) In Gregoriadis, G. (cd) Liposome Technology. CRC Press, Boca Raton. p. 157-176. 2. Amnothayanun, P.. Turton. J.A.. Uchegbu, I.F.. Florence, A.T. (1997) Pharm.
Res. 14(suppl.):s-286
OF
J.A. Bemabeu. V.Cald&n’, V. Ruz, ME. Gil-Alegre, M.A. Camacho and A.I. Torres-SuBrez. Pharmacy and Pharmaceutical Technology Department. Faculty of pharmacy. Complutense University of Madrid. 28040 Madrid. Spain. Food National Center. Carlos III Health Institute. Madrid. Spaln. Within the Spanlsh Research Plan of Residues in Foods (SRPRF). the presence of antibiotiw must be detected in a high percentage of samples using the microbiokgical technique recommended by the European Union. To guarantee the right sensitivity of the technique, nowdays, paper discs impregnated with en antibiotic very low concentration solution are used as control. As the discs must be prepared and stored by each laboratory of the SRPRF, a great variability in the results is obtained depending on me geographical area where the essay is carried out. The aim of this work is to obtain antibiotics matrix teblets vvhkh can advantageously replace to the paper discs. The matrix tablets may meet the following requirements: I) the exdpient should not have any effect on the microorganism growth; 2) homogeneous distribution of the antibiotic within the excipient, due to the antibiotk very low dose (e.g. 2.5 micmg of streptomyclne in 50 mg of excipient); 3) chemical and physically stable (stress stability test: 4O’C and 75% R.H. for 12 months). The selected excipients are: AvkelQD PH 101, Kollldon@30, Emcompress@, Orgasom 2002 ES 5 NAT 3, Ludipreas@ PEG 4000 and Predrol Q, AT5 The antlblotic-excipient mixture techniques are: 1) geometrical dilutions of the antibiotic with the excipknts; 2) antlbktk solution sprayed on the axcipients: 3) wet grenuletkn: a disolution with he antibiotic and the binder added on the exclplent mbdura. The obtained results demonstrate that the matrix tablets used as new wntrol ahow a lower variabtlttv than the pepar discs.The beat results come from: 1) m&lx tablets of Avicel or Emwmpres obtained by spray technique; 2) matrix tablets of Orgasol or Prectrol by wet granulation. ‘This wcwk is supported by Spanish Goverment (FISss).
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INVESTIGATIONS ON TOPICAL FORMULATIONS OF CLOMIPAENE CITRATE FOR TREATMENT OF HPV LESIONS E Cevher, N. 0. Sahin,A.Araman Istanbul University, Faculty of Pharmacy, Department of Phannaceutlcal Technology, Beyazit 34452, Istanbul-TURKEY Cluman Papilloma Vuus (HPV) infections are commonly seen in women and cause displastic lesions in genital region. The convwional therapy mcludes caterizatmn, cryosurgery, laser techmques and chemotherapy. rlnterferrm a-2a, podophylii, and cytostatic drugs are used in chemotherapy with limited success. Clomiphene citrate (CC), a nonsterad estrogen analogue with antiestrogen actiwty, 1s commonly used per oral m treatment of infettility in women. H.J Schti et al. prepared an ointment and a cream containing CC and applied these formulatrons to the patim with HPV topically. The therapeutic response was satisfying. Based on these data, we set the goal of our study fo develop a new topical formulation of CC for treatment of HPV displastic lesions. Bioadhesive gels with controlled release characteristics were prepared using poly(acrylic acid) derivatives. The greatest advantages of such gels are to provide controlled release of CC and to maintam the drug in the vagina for extended period of time. This reduces dosing 6equency and thus, improves patient compliance. In vitro release characteristics of CC from different formulations were investigated and compared to those of conventional creams and ointments pH of gels were measured right a&r preparation and 1 month later Shearing stickness of gels were measured using a modified adheswes tester at 2WC. In vitro release rates were determined over a predetermined time period (24 h) using the modified apparatus for disintegration of vaginal tablets described in BP at 37+2’C. Tbe favorable drug release characteristics in vitro suggest that tbrther in viva investigation of this drug delivery system in treatment of HPV lesions is warranted.
OPTIMIZED PREPARATION OF POLY(LACTIDE-CO-CLYCOLIDE)POLY(ETHYLENECLYCOL) NANOPARTICLES LOADED WITH CISPLATIN A. Beletsi(l), P. Klepetsanis(l), D.S. Ithakissios(l), S. Kounias(2), A. Stavropoulos(2) and K.Aveoustakis( 11 (I) University of Patras. Lab. of Pharmaceutical Technology, Patras 261 IO, Greece. (2) University of Athens, Dept. of Mathematics, Panepistemiopolis 15784, Athens, Greece. A central composite experimental design was applied to investigate the effect of five preparative variables on the size and drug loading of PLGA-PEG-cisplatin nanoparticles. The nanoparticles were prepared by transferring an acetone-dimethylformamide solution of polymer and drug in a stirred aqueous buffer pH 7.4 containing sodium cholate as emulsifier. The organic phase was evaporated under controlled temperature and the size and drug content of the resulting nanoparticles were determined using photon correlation spectroscopy and atomic absorption spectroscopy respectively. The preparative variables investigated were: solids concentration, aqueous to organic phase volume ratio, temperature, rate o!’organic phase addition in aqueous phase, and agitation. The size and the drug loading of the prepared nanoparticles ranged between 90-l 80 nm and O-40% respectively. The fitted model could adequately describe the experimental data. The statistical analysis showed that all preparative variables studied, except temperature, affected significantly both the size and the drug loading of nanoparticles. The size was most affected by agitation whereas the loading was Imost affected by the phase ratio. Significant interactions between the preparative variables were also observed. The desirability function approach (Derringer and Suich, J. Qual. Technol.,l2( 1980)214-2 19) was applied to determine the optimum conditions for the preparation of the PLGA-PEG-cisplatin nanoparticles.
242
244
WSCOSITY OF NIOSOME DISPERSIONS P. Anmothavanun. S. Kiri, A. T. Florence Centre.for Dmg Delivery Research,The School of Pharmacy, Universityof London, 29-39 Brunswick Square. London WClN lAX, UK
NEW CONTROL SYSTEM FOR THE DETECTION RESIDUES IN FOODS: MATRIX TABLETS*
Niosomes are colloidal dispersions formed by self-assembly of nonionic surfactants. Their capability to entrap solutes allows them to be used as drug carriers.‘~* Little has been published on the rheological characteristics of these dispersions or of their phospholipid counterparts. We have shown that the viscosity of niosomes is affecled by temperature and shape of the vesicles. Further studies have been performed to investigate other factors which affect their rheology. Vesicles formed mainly by Span 60 (sorbitan monostearate) and cholesterol were used as models; with an addition of a hydrophilic surfactant, Solulan C24 (poly 24 oxyethylene cholesteryl ether); or a charged surfactant, dicetyl phosphate (DCP). The relative viscosity of the dilute vesicle dispersions was measured against water using a suspended level dilution viscometer. The viscosity of the dispersions increases on increasing the vesicle concentration or reducing the vesicle size. Increasing the amount of Solulan C24 in the vesicle membranes results in higher viscosity due to the increased hydration. The presence of NaCl in the medium reduces the viscosity of DCPcontaining vesicles as the electric diffuse layers are suppressed. The factors affecting the viscosity of these dispersions are complex. Intqretation of intrinsic viscosity values is complicated by the lamellarity and perhaps flexibility of some vesicle formulations in flow, but an attempt has nevertheless heen made to estimate hydration from the data. Acknowledgements: P.A. was supported by the Government Phamweutical Organisation. Thailand. References: I. Florence, A.T. (1993) In Gregoriadis, G. (cd) Liposome Technology. CRC Press, Boca Raton. p. 157-176. 2. Amnothayanun, P.. Turton. J.A.. Uchegbu, I.F.. Florence, A.T. (1997) Pharm.
Res. 14(suppl.):s-286
OF
J.A. Bemabeu. V.Cald&n’, V. Ruz, ME. Gil-Alegre, M.A. Camacho and A.I. Torres-SuBrez. Pharmacy and Pharmaceutical Technology Department. Faculty of pharmacy. Complutense University of Madrid. 28040 Madrid. Spain. Food National Center. Carlos III Health Institute. Madrid. Spaln. Within the Spanlsh Research Plan of Residues in Foods (SRPRF). the presence of antibiotiw must be detected in a high percentage of samples using the microbiokgical technique recommended by the European Union. To guarantee the right sensitivity of the technique, nowdays, paper discs impregnated with en antibiotic very low concentration solution are used as control. As the discs must be prepared and stored by each laboratory of the SRPRF, a great variability in the results is obtained depending on me geographical area where the essay is carried out. The aim of this work is to obtain antibiotics matrix teblets vvhkh can advantageously replace to the paper discs. The matrix tablets may meet the following requirements: I) the exdpient should not have any effect on the microorganism growth; 2) homogeneous distribution of the antibiotic within the excipient, due to the antibiotk very low dose (e.g. 2.5 micmg of streptomyclne in 50 mg of excipient); 3) chemical and physically stable (stress stability test: 4O’C and 75% R.H. for 12 months). The selected excipients are: AvkelQD PH 101, Kollldon@30, Emcompress@, Orgasom 2002 ES 5 NAT 3, Ludipreas@ PEG 4000 and Predrol Q, AT5 The antlblotic-excipient mixture techniques are: 1) geometrical dilutions of the antibiotic with the excipknts; 2) antlbktk solution sprayed on the axcipients: 3) wet grenuletkn: a disolution with he antibiotic and the binder added on the exclplent mbdura. The obtained results demonstrate that the matrix tablets used as new wntrol ahow a lower variabtlttv than the pepar discs.The beat results come from: 1) m&lx tablets of Avicel or Emwmpres obtained by spray technique; 2) matrix tablets of Orgasol or Prectrol by wet granulation. ‘This wcwk is supported by Spanish Goverment (FISss).