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Lactose particles are used in inhalation powders: Do they penetrate into the lungs?
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TRANSDERMAL DRUG DEJBFtRY AS A WAY TO ADJUSTMENTS OF DRUG ACTJS’ITY. A. E. Vasiliex V. N. Tokhmakhchi and R. G. Vasilov
FILTRATION STUDY OF TWO PHARMACEUTICAL GRADE PHYLLOSILICATES GELS: DESORPTlVllY OF FILTER CAKES. C. Viseras’ and A. L6pez-Gaiindo’ ‘Dpto. Farmacia Tecnologia Farmadutica, FcFarmacia, Univ. Granada. Campus Cattuja. s/n, 18071, Granada, Spain. 21nstiiutoAndaluz de Ciencias de la Tierra. (CSIC-UGR), Spain.
Institute of Biotechnology, 117246, Russia
8 Nat&my
prnezd,
Moscow,
It is well recognized that phatmaoologioal activity of drugs is depend on ways and schedule of drug delivery. This is especially so when it applied to controlled release drug formulation. The. goal ofthis investigation is demonstration of appearance of the new properties for wolI known drugs delivered transdernmhy as compared to other form of the same drugs. We propared transcJermal drug delivery systems (TDDS) containing oytizine, phonazepam or clonidin using ccmiversaln hydrophilic matrix proposed earlier by us. All TDDS were drug-in-adhesive type. Cytizine, being respirstion snsleptica io injectable fom was converted in Strong antismoking drug TDDS Cypnrcutan. This is the Srst nicotinefree antismoking TDDS ( up to 76% of abstinent patients in clinical trials). Peroral phenazpatn is a high potent night tranquil&r, but in TDDS Phenapercuten it transRornmd in day tran~ owing to lack of hypnotic and myorohtxant properties. Clonidine used mostly in peroral or psreotheral form for treatment of hypertension crisis, io TDDS is rather mild antihypertensive agent clopercuteo reoonunendori for long-term treattnent of hypertension. We supposed those facts are the result of absence of peak
This study was undertaken to characterise. by means of a controlled onedimenslonal filtration, the structure of water disperse systems elaborated with two commercial samples of attapulgite. i.e., Pharmasorbc Colloidal and Regular. 73% and 47% respectively consisted on palygorskite, the rest being calcite and illite on PHC and smectiie and quartz on PHR. Dispersions of each material at 2% and IO % w/v in distilled water were elaborated using a high shear rotor-stator mixer. 1000 rpm and 8000 rpm during 1 and 10 minutes were the rotor speeds and times used in the interposition (i.e.. four different mixing energies). 95W of the particles were under 5 microns on both samples resulting in flocculated colloidal systems when dispersed in water. Filter cakes obtained consisted on a set of interpenetrating networks of partiie aggregates with the attributes of a weak solid. Desorptivii values were found to be from 9.157 x E-Q to 1.728 E-4 in the case of PHC. deoendino on the mixing conditions and solid fraction of the dispersion, “and from 1I. 103 E-4 to 3.576 E-4 on PHR systems. A inverse relation was found between the applied mixing-energies and desorptiiity values, enabling us to predict the structure of a model system as a function of mineral content, solid fraction and mixing energy.
concentration of drug in blood in course of transdermal delivery of the drugs.
author gratefully acknowledge the invaluable First encouragement and support provided by Dr. G.H. Meeten (SCR, Cambridge, UK). This work was supported by project PB95-1271. CO2-01 (DGES). Ministerlo de Educacibn y Cultura, Spain.
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LACTOSE PARTICLES ARE USED IN INHALATION POWDERS: DO TREY PENETRATEINTO TEE LUNGS?
MICROSTRUCTURAL PACKING PARAMETERS ON BtNARY COMPONENT TABLETS AND CORRELATION WITH THEIR DISINTEGRANT PROFILES C. Vlseras’, A. Yebra-Rodriguez’ and A. L6pez-Gatlndo’ ‘Dpto. Farmacia Tecnologla Farmadutica, Fc. Farmacia, Univ. Granada. Campus Cartuja, s/n, 18071, Granada, Spain. ?nstituto Andaluz de Ciencias de la Tierra. (CSIC-UGR), Spain
M. Karhu',J. Ku&lo?, T. Kaup@nen*and &Y&&P! ‘Department of Pharmaceutics, University of Kuopio, Kuopio (Finland) ‘Department of Clinical Physiology, University Hospital of Kuopio, Kuopio (Finland)
Dry powder dosage forms arc generally formulated by mixing the cohesive micronized drug particles with the larger car& particles. Lactose is commonly used csnier. Carrier enhances the flowability of powder mixtures and therefore enables dosing. During the inhalation, the drug particles arc dispersed f&n the surface of carrier particles. The aim of this study was to compare how diierent qualities of w”rclab&d lactose carriers deposite in the lungs. The sizes of the labelled and unlabelIed lactose monohydrate particles were compared by using Laser Particle Sir. Distribution of radiolabel between different Particle size fraction were dckrmined using * cascade impactor. The in vtvo dcposition of three different kind of lactose carrier was investigated in ten healthy volunteers using technique of gammascintigraphy. In addition, redisperssion of budesonide from different carrier material war evaluated. According to the validation data the Properties of the lactose particles remained unchanged during the labelhog Processes. pulmonary deposition varied between 2.5 - 3.3 %. Tberc was statistically significant ditkrence between highest and lowest dePosition vahms (Lactose A / Lactose B) @
Image analysis and stereology results were correlated to disintegration profiles of compacts obtained with samples of phyllosilicates with dierent morphologies (i.e., laminar or fibrous). Tablets (500 f 5 mg) were obtained by direct compression on a conventional tablet press. Each tablet contained IO mg (20%) of phyllosilicate and 490 (80%) of paracetamol DC. Compacts were kept under 40% relative humidity and room temperature (20 to 25 “C) for at least 48 hours before study. Then microphotographs of internal microstructure were obtained by using a Zeiss’ DSM 950 scanning electron microscope on axial sections of each tablet. The image frame was 512 x 512 pixels size. Volumetric measurements were calculated on the basis of stereology from two dimensional images applying a shape factor equal to 4x area/perimete?. A dependence was found between particle morphology parameters, aggregation state, micro-porosity, and disintegration results, including maximum water uptake values and disintegration times. This was possible on the case of fibrous particles but not for the laminar ones, as a consequence of the influence of interlayer ions on the swelling on these phyllosilicates. The study of tablets microstructure by image analysis and stereology is proposed as an adequate method for indirect study of disintegration ability on non-swelling disintegrants as those studied. This work was supported by project PBQ5-1276CO2-01 (DGES). Ministerio de Educacf6n y Cultura, Spain.
301
303
TRANSDERMAL DRUG DEJBFtRY AS A WAY TO ADJUSTMENTS OF DRUG ACTJS’ITY. A. E. Vasiliex V. N. Tokhmakhchi and R. G. Vasilov
FILTRATION STUDY OF TWO PHARMACEUTICAL GRADE PHYLLOSILICATES GELS: DESORPTlVllY OF FILTER CAKES. C. Viseras’ and A. L6pez-Gaiindo’ ‘Dpto. Farmacia Tecnologia Farmadutica, FcFarmacia, Univ. Granada. Campus Cattuja. s/n, 18071, Granada, Spain. 21nstiiutoAndaluz de Ciencias de la Tierra. (CSIC-UGR), Spain.
Institute of Biotechnology, 117246, Russia
8 Nat&my
prnezd,
Moscow,
It is well recognized that phatmaoologioal activity of drugs is depend on ways and schedule of drug delivery. This is especially so when it applied to controlled release drug formulation. The. goal ofthis investigation is demonstration of appearance of the new properties for wolI known drugs delivered transdernmhy as compared to other form of the same drugs. We propared transcJermal drug delivery systems (TDDS) containing oytizine, phonazepam or clonidin using ccmiversaln hydrophilic matrix proposed earlier by us. All TDDS were drug-in-adhesive type. Cytizine, being respirstion snsleptica io injectable fom was converted in Strong antismoking drug TDDS Cypnrcutan. This is the Srst nicotinefree antismoking TDDS ( up to 76% of abstinent patients in clinical trials). Peroral phenazpatn is a high potent night tranquil&r, but in TDDS Phenapercuten it transRornmd in day tran~ owing to lack of hypnotic and myorohtxant properties. Clonidine used mostly in peroral or psreotheral form for treatment of hypertension crisis, io TDDS is rather mild antihypertensive agent clopercuteo reoonunendori for long-term treattnent of hypertension. We supposed those facts are the result of absence of peak
This study was undertaken to characterise. by means of a controlled onedimenslonal filtration, the structure of water disperse systems elaborated with two commercial samples of attapulgite. i.e., Pharmasorbc Colloidal and Regular. 73% and 47% respectively consisted on palygorskite, the rest being calcite and illite on PHC and smectiie and quartz on PHR. Dispersions of each material at 2% and IO % w/v in distilled water were elaborated using a high shear rotor-stator mixer. 1000 rpm and 8000 rpm during 1 and 10 minutes were the rotor speeds and times used in the interposition (i.e.. four different mixing energies). 95W of the particles were under 5 microns on both samples resulting in flocculated colloidal systems when dispersed in water. Filter cakes obtained consisted on a set of interpenetrating networks of partiie aggregates with the attributes of a weak solid. Desorptivii values were found to be from 9.157 x E-Q to 1.728 E-4 in the case of PHC. deoendino on the mixing conditions and solid fraction of the dispersion, “and from 1I. 103 E-4 to 3.576 E-4 on PHR systems. A inverse relation was found between the applied mixing-energies and desorptiiity values, enabling us to predict the structure of a model system as a function of mineral content, solid fraction and mixing energy.
concentration of drug in blood in course of transdermal delivery of the drugs.
author gratefully acknowledge the invaluable First encouragement and support provided by Dr. G.H. Meeten (SCR, Cambridge, UK). This work was supported by project PB95-1271. CO2-01 (DGES). Ministerlo de Educacibn y Cultura, Spain.
302
304
LACTOSE PARTICLES ARE USED IN INHALATION POWDERS: DO TREY PENETRATEINTO TEE LUNGS?
MICROSTRUCTURAL PACKING PARAMETERS ON BtNARY COMPONENT TABLETS AND CORRELATION WITH THEIR DISINTEGRANT PROFILES C. Vlseras’, A. Yebra-Rodriguez’ and A. L6pez-Gatlndo’ ‘Dpto. Farmacia Tecnologla Farmadutica, Fc. Farmacia, Univ. Granada. Campus Cartuja, s/n, 18071, Granada, Spain. ?nstituto Andaluz de Ciencias de la Tierra. (CSIC-UGR), Spain
M. Karhu',J. Ku&lo?, T. Kaup@nen*and &Y&&P! ‘Department of Pharmaceutics, University of Kuopio, Kuopio (Finland) ‘Department of Clinical Physiology, University Hospital of Kuopio, Kuopio (Finland)
Dry powder dosage forms arc generally formulated by mixing the cohesive micronized drug particles with the larger car& particles. Lactose is commonly used csnier. Carrier enhances the flowability of powder mixtures and therefore enables dosing. During the inhalation, the drug particles arc dispersed f&n the surface of carrier particles. The aim of this study was to compare how diierent qualities of w”rclab&d lactose carriers deposite in the lungs. The sizes of the labelled and unlabelIed lactose monohydrate particles were compared by using Laser Particle Sir. Distribution of radiolabel between different Particle size fraction were dckrmined using * cascade impactor. The in vtvo dcposition of three different kind of lactose carrier was investigated in ten healthy volunteers using technique of gammascintigraphy. In addition, redisperssion of budesonide from different carrier material war evaluated. According to the validation data the Properties of the lactose particles remained unchanged during the labelhog Processes. pulmonary deposition varied between 2.5 - 3.3 %. Tberc was statistically significant ditkrence between highest and lowest dePosition vahms (Lactose A / Lactose B) @
Image analysis and stereology results were correlated to disintegration profiles of compacts obtained with samples of phyllosilicates with dierent morphologies (i.e., laminar or fibrous). Tablets (500 f 5 mg) were obtained by direct compression on a conventional tablet press. Each tablet contained IO mg (20%) of phyllosilicate and 490 (80%) of paracetamol DC. Compacts were kept under 40% relative humidity and room temperature (20 to 25 “C) for at least 48 hours before study. Then microphotographs of internal microstructure were obtained by using a Zeiss’ DSM 950 scanning electron microscope on axial sections of each tablet. The image frame was 512 x 512 pixels size. Volumetric measurements were calculated on the basis of stereology from two dimensional images applying a shape factor equal to 4x area/perimete?. A dependence was found between particle morphology parameters, aggregation state, micro-porosity, and disintegration results, including maximum water uptake values and disintegration times. This was possible on the case of fibrous particles but not for the laminar ones, as a consequence of the influence of interlayer ions on the swelling on these phyllosilicates. The study of tablets microstructure by image analysis and stereology is proposed as an adequate method for indirect study of disintegration ability on non-swelling disintegrants as those studied. This work was supported by project PBQ5-1276CO2-01 (DGES). Ministerio de Educacf6n y Cultura, Spain.