Kniga na apstrakti book of abstrcts

Osloboduvawe na 5-Aminosalicilna kiselina 
od citozan-kalcium-alginatni mikro~esti~ki; 
vlijanie na formulaciskite promenlivi 
K. Mladenovska
1
,
O. Krio
2
, R. S. Rai~ki
1
, M. G. Dodov
1
, M. S. Crcarevska
1
, 
E. I. Janevi}
3
, Z. Kavrakovski
1
, K. Gora~inova
1
1
Farmacevtski fakultet i 
3
Medicinski fakultet, 
Univerzitet „Sv. Kiril i Metodi“, Skopje, Makedonija; 
2
Farmacevtski fakultet, Univerzitet Angers, Angers, Francija
Podgotveni se citozan-Sa-alginatni mikro~esti~ki so potencijal za kontrolirano i naso~eno
osloboduvawe na 5-ASK vo kolonot posle oralna primena. Celta na ispituvaweto e da se oceni vlijani-
eto na formulaciskite promenlivi vrz osloboduvaweto na 5-ASK vo sredini so razli~na rN, soli i enz-
imi koi imitiraat in vivo uslovi. Za da se dobijat ~esti~ki pomali od 15 mm, primeneta e tehnika na
rasprsnuvawe so su{ewe so koja se dobieni alginatni mikro~esti~ki vo koi e inkorporirana 5-ASK.
Podgotvenite mikro~esti~ki se vneseni vo rastvor na citozan i kalcium hlorid so cel da se dobie sta-
bilen i mehani~ki otporen mikrosistem. Koristeni se tri vida na natrium alginat so sli~na Mm, razli~na
viskoznost i razli~en odnos na guluronska i manuronska kiselina i dva vida na citozan so razli~na
Mm/viskoznost i ist stepen na deacetilacija (>85%). Postapkata na vkrsteno mre`uvawe/polielektrolit-
no kompleksirawe e sproveduvana pri koncentraciski ograni~uvawa na alginatot (1 i 3% m/m), citozan-
ot (0.1 i 0.5% m/m) i CaCl
2
(0.5 i 5% m/m) i ograni~uvawa vo rN na mediumot (3.5 i 4.5). Za optimizacija na
pove}ekratnite odgovori, koristen e kombiniran frakciski faktorijalen dizajn na 2 i 3 nivoa (14 serii,
programa Nemrod). Sporedbata na brzinata na osloboduvawe e vr{ena vo rN 1.2 (prazen `eludnik), 6.8
(jejunum), rN gradienten metod (rN od 1.2 do 7.5) i enzimski metod (izmena na fosfatniot pufer rN 6.8 so
suspenzija na kekalna sodr`ina od staorec vo bikarbonaten pufer, so dodatok na SO2 za da se odr`i anaer-
obnata sredina).
Podgotveni se ~esti~ki so povr{inski polne` pome|u -33.8 i 10.3 mV, golemina pome|u 5 i 14 mm,
sodr`ina na Ca
2+
pome|u 2.5 i 5.5 % i aktuelna sodr`ina na lek do 8.72%, odnosno 16.59% (teoretska
sodr`ina 14% i 33%, soodvetno). SEM upatuva na prifatliva sferi~na morfologija, no i plosnati,
diskovidni ~esti~ki. Vizuelizacijata so KLSM poka`uva lokalizacija na citozanot dominantno vo yidot
na ~esti~kite, dodeka alginatot e homogeno distribuiran niz ~esti~kite. 5-ASK e dispergirana niz
~esti~kite na molekularno nivo (DSK i difrakcija so H-zraci). 
Analizata na podatocite upatuva na aktivno vlijanie na koncentracijata na CaCl
2
vrz oslobodu-
vaweto na 5-ASK vo rN 1.2 za prose~noto vreme na prestoj vo `eludnikot (2 ~). Vo ovoj period, pobrzo
osloboduvawe se zabele`uva kaj seriite podgotveni od alginat so povisok udel na M edinici i relativno
povisoka viskoznost. Povisokata sodr`ina na Ca
2+ 
vo gelira~kiot medium uslovuva posporo oslobodu-
vawe vo site mediumi bez ogled na vidot na primenetite polimeri. Pri osloboduvawe na 5-ASK vo rN 6.8,
posporo osloboduvawe se javuva koga se koristi citozan so pogolema Mm. Najsporo osloboduvawe se
zabele`uva kaj seriite podgotveni od alginat so visok udel na G edinici zaradi povisokata mehani~ka
otpornost/stabilnost kon monovalentni katjoni. 
Vo rN 1.2, alginatot e protoniziran vo nerastvorliva forma so babre~ki svojstva koi go objasnu-
vaat maloto koli~estvo na osloboden lek. Pozitivno naelektriziranite grupi na citozanot reagiraat so
negativnite na alginatot i 5-ASK usporuvaj}i go babreweto t.e. osloboduvaweto na 5-ASK. Brzinata na
osloboduvawe vo rN 6.8 e sli~na so brzinata vo rN 1.2. Prisustvoto na soli i enzimi gi modificira
determinira~kite faktori na osloboduvaweto zgolemuvaj}i ja rN, poroznosta i brzinata na degradacija
na matricata. Higu~ieviot model upatuva na osloboduvawe vodeno so rastvorlivosta i difuzijata na 5-
ASK. Difuziskite eksponenti spored op{tata eksponencijalna ravenka upatuvaat na vidoizmeneta Fikova
difuzija kontrolirana so relaksacija, erozija i degradacija na polimerite.
Macedonian pharmaceutical bulletin 53 (1,2) 43-44 (2007)
PP - 2
44
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Spray-dried chitosan-Ca-alginate microparticles for colon delivery of 5-FU
M. Glavas Dodov
1
, A. A. Hincal
2
, S. Calis
2
, M. Simonoska Crcarevska
1
, 
N. Geskovski
1
, K. Goracinova
1
1
Institute of Pharmaceutical Technology, Faculty of Pharmacy, 
University „Ss Cyril and Methodious“, Vodnjanska 17, 1000 Skopje, Macedonia
2
Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
The aim of the present study was to formulate microparticulated drug delivery systems (MP`s DDS) as a
carriers of 5-FU for colon targeting via per oral route with proper muco/bioadhesive characteristics and controlled
release properties.
Chitosan, low viscous, was purchase from Fluka BioChemica (Buchs, Switzerland). Sodium-alginate (Protanal
LF10/60) was kindly donated from FMC BioPolymer, Norway. CaCl
2
was supplied from Alkaloid, Macedonia and
5-Fluorouracil (5-FU) from EBEWE Pharma, Germany. Hydroxypropyl methylcellulose phthalate (H55) was pur-
chase from Shin Etsu Chemical Co. Ltd., Japan. 
Spray-dried enteric coated (H55) particles of 5-FU with mean diameter of 3.15 mm were prepared and incor-
porated as a core material into chitosan-Ca-alginate beads (sample 1E, containing 1.25% of CaCl
2
and sample 2E,
containing 2.5% of CaCl2) by one step spray-drying process [1]. Chitosan-Ca-alginate micropartilces with pure 5-FU
were also prepared (samples 1 and 2).
Proposed method allowed formation of spherical particles with relatively smooth surface and high produc-
tion yield, mean diameter 4.45-6.79 
µm, unimodal narrow size distribution and high encapsulation efficiency of 5-
FU (~70%). Considering the effect of different pH media on the swelling behavior of the particles, it can be con-
cluded that in water and acidic media only a small degree of swelling was observed, but at pH 6.8 and 7.4 rapid
swelling occurred. Also, the concentration of CaCl2 (1.25 and 2.5%) significantly affects the swelling behaviour of
the particles. Prepared formulations showed a positive value of the zeta potential in water and in buffer systems at
pH 2.0, 6.8 and 7.4. These observations are of great importance, since positive charge originating from chitosan is
necessary for the interaction with negatively charge mucus, and consequently bioadhesion, which was further con-
firmed with in vitro adsorption studies with pig mucin [2]. Also, the extent of adsorption of mucin onto particles sur-
face was dependent upon the concentration of the cross-linking agent used for microparticles preparation and the pH
value of the medium during the mucoadhesion testing [3].  
Coating of the 5-FU with H55, efficiently retained the drug inside the particles, maintaining ~80% of the
initial drug loaded after 2 h at pH 2.0. A comparatively fast release was observed at pH 6.8 and 7.4 due to the swelling
of the particles and pH-dependent solubility of H55. In these microparticles, initial swelling and buffer gaining inside
the beads leads to matrix rehydration and dissolution of H55, afterwards the drug delivery during the time of the dis-
solution study was controlled from chitosan-Ca-alginate matrix.
Having in mind the presented physico-chemical and biopharmaceutical properties of the prepared particles,
together with their expressive muco/bioadhesive potential, further studies will be focused on coating of the prepared
formulations in an order to increase their stability in physiological fluids and to target them to the colon region. In
this way, colon cancer could be treated locally, opening a new therapeutic potential for this drug carrier systems.
Macedonian pharmaceutical bulletin 53 (1,2) 45-46 (2007)
PP - 3
45
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Sprej-su{eni citozan-kalcium-alginatni mikro~esti~ki so 5-FU
za naso~eno deluvawe vo kolon
M. Glava{ Dodov
1
, A. A. Hin~al
2
, S. ^alis
2
, M. Simonoska Crcarevska
1
, 
N. Ge{kovski
1
i K. Gora~inova
1
1
Institut za Farmacevtska tehnologija, Farmacevtski fakultet, 
Univerzitet „Sv. Kiril i Metodij“, Vodwanska 17, 1000 Skopje, Makedonija
2
Farmacevtski fakultet, Haxitepe Univerzitet, Ankara, Turcija
Celta na trudot be{e formulirawe na mikropartikulirani sistemi kako nosa~i na 5-FU so
naso~eno deluvawe vo kolonot po nivna oralna aplikacija, so soodvetni muko/bioadhezivni karakteris-
tiki i kontrolirano osloboduvawe na enkapsuliranata lekovita supstancija. 
Mikro~esti~kite so 5-FU (EBEWE Pharma, Germany) bea podgotveni so koristewe na citozan so
niska viskoznost (Fluka BioChemica; Buchs, Switzerland) i natrium alginat-Protanal LF10/60 (FMC BioPolymer,
Norway). Kako agens za vkrstenopovrzuvawe be{e koristen CaCl
2
(Alkaloid, Macedonia). 
Sprej-su{enite acidorezistentno-oblo`eni (hydroxypropyl methylcellulose phthalate (H55); Shin Etsu
Chemical Co. Ltd., Japan) ~esti~ki na 5-FU, so sreden  dijametar od 3.15 
µm, bea inkorporirani kako jadren
materijal vo citozan-Ca-alginatni mikro~esti~ki (primerok 1E, so 1.25% na CaCl
2
i primerok 2E, so 2.5%
na CaCl
2
) so ednostepena postapka na sprej-su{ewe [1]. Vo isto vreme bea podgotveni i citozan-Ca-algi-
natni mikro~esti~ki so ~ist 5-FU (primeroci 1 i 2). 
Tehnikata na sprej-su{ewe ovozmo`i formirawe na sferi~ni partikuli so relativno mazna povr-
{ina, visok proizvodstven prinos, sreden dijametar 4.45-6.79 
µm, so unimodalna normalna distribucija i
visoka efikasnost na enkapsulacija na 5-FU (~70%). Ispituvawata na stepenot na babrewe na ~esti~kite
vo puferi so razli~na pH i jonska ja~ina uka`aa deka vo voda i kisela sredina ne doa|a do zna~ajni promeni
na sredniot volumenski dijametar na mikro~esti~kite za razlika od izrazeniot stepen na babrewe pri
nivno tretirawe so fosfatni puferi so pH 6.8 i 7.4. Vo isto vreme, variraweto na koncentracijata na
agensot za vkrsteno povrzuvawe (1.25 i 2.5% CaCl
2
), poka`a zna~ajno vlijanie vrz stepenot na babrewe na
~esti~kite. Podgotvenite primeroci na mikro~esti~ki se karakteriziraa so pozitiven polne` {to e od
osobeno zna~ewe za mo`nata interakcija so negativno naelektriziraniot mukus i posledovateno bioad-
hezijata, {to ponatamu be{e potvrdeno so in vitro adsorpciskite studii so svinski mucin [2]. Pri toa, kon-
centracijata na agenot za vkrsteno-povrzuvawe kako i pH na mediumot vo koj bea sprovedeni ispituvawa-
ta poka`aa zna~ajno vlijanie vrz % na vrzan mucin za povr{inata na ~esti~kite [3]. Oblo`uvaweto na
5-FU so H55, efikasno go suprimira osloboduvaweto na lekovitata supstancija vo kisela sredina. Vo fos-
fatni puferi so pH 6.8 i 7.4, zabele`ano be{e zabrzano osloboduvawe na 5-FU kako rezultat na babrewe-
to na ~esti~kite i pH zavisnata rastvorlivost na H55. Kaj ovie sistemi, inicijalnoto babrewe i pene-
tracijata na disolucioniot medium niz porite na partikulite, rezultira{e se rehidracija na matriksot
i rastvarawe na H55, po {to brzinata na osoboduvaweto na 5-FU be{e kontrolirana od osobinite na
citozan-Ca- alginatnata matrica.
Imaj}i gi vo predvid navedenite fizi~ko-hemiski i biofarmacevtski karakteristiki na pod-
gotvenite formulacii, kako i izrazeniot muko/bioadheziven potencijal, ponatamo{nite istra`uvawa }e
bidat naso~eni kon funkcionalizacija na pogotvenite formulacii, so cel da se zgolemi nivnata stabil-
nost vo fiziolo{kite te~nosti i celno da se naso~at kon mestoto so maligni promeni vo kolonot.
Macedonian pharmaceutical bulletin 53 (1,2) 45-46 (2007)
PP - 3
46
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Orally disintegrating tablet: Formulation design and Optimisation
using Response surface methodology
B. Nestorovska-Gjosevska, M. Glavas-Dodov, K. Goracinova
Department of Pharmaceutical Technology, Faculty of Pharmacy, 
University „Ss Cyril and Methodius“, Vodnjanska 17,1000 Skopje, Macedonia
The objective of the present study was to develop Diazepam orally disintegrating tablets and to optimize
tablets characteristics. Experimental research methodology represents efficient approach for solving optimization
problems of the excipient composition aimed to obtain a product with the required characteristics. Adopting such an
experimental approach means defining the problem which one is going to cope with by determining the objectives,
the possible constraints on the component proportions, and the response variables under study. In this way, the exper-
imental region of interest and the strategy to follow can be defined. In this study tablet characteristics were optimized
using response surface methodology.
Tablets were prepared by direct compression of mixture containing mannitol, copovidone, crosspovidone fla-
vor and lubricant. A full factorial design for 2 factors at 3 levels each was applied to investigate the influence of 2 for-
mulation variables on the mechanical strength/hardness, the percent of friability, disintegration time and dissolution
of the poorly soluble active ingredient. The amounts of copovidone and crosspovidone were taken as independent
variables. All data were analyzed by using statistical program. 
The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage
form, desired dissolution rate and mechanical properties, tablets should be prepared using an optimum concentra-
tion of crosspovidone and copovidone. A contour plot is also presented to graphically represent the effect of the inde-
pendent variables on the tablet hardness, disintegration time, percentage friability and dissolution. A checkpoint batch
was also prepared to prove the validity of the evolved mathematical model. 
The most significant effect on the hardness of the tablets shows the binding agent copovidone. Increasing
the quantity of copovidone increases the hardness of the tablets.
The most significant effect on the friability of the tablets has copovidone, although effect on the friability
due to the interaction between copovidone and crosspovidone is also present. With increasing the content of copovi-
done the percent of friability of the tablets decreases.
The quantity of the copovidone and crosspovidone presents the main effect on the tablet disintegration.
Interaction among copovidone and crosspovidone shows significant effect on the disintegration process, also.
Increasing the quantity of crosspovidone and decreasing the quantity of copovidone decreases the time of disinte-
gration of the tablets. Decreasing the disintegration time the influence of this parameter on the dissolution time and
of the active component is completely avoided and the dissolution rate and time will depend only on the character-
istics of the active ingredient, which if needed might be modified as well. Based on the quantitative effect of the
polynomial equations generated by RSM, the optimum formulation from RS design could be formulation with ade-
quate hardness, friability and disintegration time less than 20 sec. Such formulation/s contains copovidone 2.75%
and crosspovidone in a quantity of 3-5%. 
3 level factorial design allowed us to obtain ODT with rapid disintegration and dissolution of the active ingre-
dient with desirable properties of low tablet friability and appropriate mechanical strength (hardness) of the tablet. The
systematic formulation approach helped in understanding and defining the effect of formulation processing variables.
Macedonian pharmaceutical bulletin 53 (1,2) 47-48 (2007)
PP - 4
47
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Peroralna disperzibilna tableta: Formulaciski dizajn i
Optimizacija so primena na Response surface Metodologija
B. Nestorovska-\o{evska, M. Glava{-Dodov, K. Gora~inova
Institut za farmacevtska tehnologija i biofarmacija, Farmacevtski fakultet, 
Univerzitet „Sv. Kiril i Metodij“, Vodwanska 17, 1000 Skopje, Makedonija
Cel na ovoj trud be{e razvoj na diazepam peroralna disperzibilna tableta i optimizacija na karak-
teristikite na tabletata. Eksperimentalnata istra`uva~ka metodologija pretstavuva efikasen pristap
kon re{avawe na optimizaciskite problemi na eden formulator so cel da se dobie proizvod so prethod-
no utvrdeni karakteristiki. Vo ovaa studija tabletnite karakteristiki se optimizirani so primena na
response surface metodologijata (RSM).
Tabletite bea podgotveni so direktna kompresija na me{avina od manitol, kopovidon, krospovi-
don, aroma i sredstvo za lubrikacija.
Be{e primenet faktorijalen dizajn so dva faktori, sekoj postaven na 3 nivoa, so cel da se ispita
efektot na dvete promenlivi vrz mehani~kata jakost/cvrstinata, procentot na frijabilnost, vremeto na
dezintegracija na tabletite i brzinata na disolucija na te{ko rastvorlivata aktivna komponenta. 
 Kako
nezavisni promenlivi bea zemeni koli~inite na kopovidon i krospovidon. Dobienite rezultati bea anal-
izirani so primena na soodvetna statisti~ka programa.
Rezultatite od multipnata regresija poka`aa deka za da se dobie dozirana forma so mnogu brza
dezintegracija, i soodvetna brzina na disolucija, istvremeno so potrebni mehani~ki svojstva, tabletite
treba da sodr`at optimalna koncentracija na kopovidon i krospovidon. 
Efektot na nezavisnite promenlivi na cvrstinata na tabletata, vremeto na dezintegracija, pro-
centot na frijabilnost i disolucijata grafi~ki e pretstaven so soodvetni response surface grafi~ki
prikazi. Matemati~kiot model na diazepam disperzibilnite tableti dobien preku response surface diza-
jnot be{e primenet pri podgotovka na optimizirana formulacija na disperzibilna tableta.
Faktorijalniot dizajn na 3 nivoa ovozmo`i da se dobie peroralna disperzibilna tableta so mnogu
brza dezintegracija i disolucija na aktivnata komponenta, so zadovolitelna frijabilnost i soodvetna
mehani~ka jakost (cvrstina) na tabletite. 
Macedonian pharmaceutical bulletin 53 (1,2) 47-48 (2007)
PP - 4
48
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Developing applicable integfrated pharmaceutical quality system 
with risk-based approach
Nada Popstefanova, Sonja Sterjevska, Miroslava Ilievska
ALKALOID A.D. - Skopje, Pharmaceutical, Chemical and Cosmetic Industry
Blvd.  Aleksandar Makedonski 12, 1000Skopje, Republic of Macedonia
Goal: Development and harmonization of standards and guidelines, strongly impacts quality systems of phar-
maceutical industries. In ALKALOID-PC Pharmaceuticals we have established our Quality & Environmental System
based on cGMP guidelines, and ISO 9001 (Quality Management) and ISO 14001 (Environmental Management) stan-
dards. Developing and maintaining an applicable integrated pharmaceutical quality system with risk-based approach
and the concept “Quality by Design” is always a challenge.
ALKALOID-PC Pharmaceuticals has introduced quality risk management as part of integrated quality man-
agement concerning in the fields of documentation, training and education and some quality items like defects, CAPA
etc. In our procedure, Q9 is a systemic process oriented approach to decision making and is applied to processes,
products, equipment, environmental aspects, premises, computer systems, methods etc. Our goal is to integrate Q8,
Q9 and Q10.  In this way, we are managing important GMP and business risks, in order to distinguish model of inte-
grated quality system with continual improvements.
Methods: There are very important recommendations, which should be fulfilled like: the FDA’s initiative on
pharmaceutical quality for the 21
st
Century ; the scientific opportunity  and the risk assessment and mitigation. 
Defining formulation using quality by design method, gives opportunity for efficient, quality and save med-
icines, as well as real-time and cost market supply. We use the method of evaluation of risk assessment in all process-
es and formulations.
Results: We monitor and evaluate processes with feedback loops, to measure, analyze, plan, act and review
to identify trends and demonstrate control/need for action, to manage undesirable occurrences (deviations, com-
plaints, inspection findings), to implement and monitor corrective and preventive actions, to manage/implement
change and monitor the effect of change. 
Product quality and performance are achieved and assured by design of effective and efficient manufactur-
ing processes.
Conclusion: The outcome is making opportunity to improve and optimize processes, equipment, facilities, sys-
tems and procedures. It our way to control processes and products and be responsible for greater self-management of
improvements and changes. In this way we change the schema of existing quality system -Process model to the schema
of target model of quality system –Model of integrated quality / sustainable quality / continuous improvement.
Macedonian pharmaceutical bulletin 53 (1,2) 49 (2007)
PP - 5
49
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

In vitro evaluation of 5-Fluorouracil-loaded enteric coated PLGA
microparticles prepared by spray-drying technique
B. Arica
1
, S. Calis
1
, K. Goracinova
2
, A. A. Hincal
1
1
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sihhiye-Ankara / Turkey
2
University “Ss.Cyril and Methodius” Faculty of Pharmacy, 1000 Skopje, Macedonia
In the present study, the enteric coated PLGA microparticles containing 5-Fluorouracil (5-FU) were pro-
duced by a spray-drying technique. The properties of the 5-FU loaded microparticles such as the size, the morphol-
ogy, the zeta potential and encapsulation efficiency were investigated as a function of the concentration of the poly-
mer (5.0% - 10% w/v) and drug loading (2.5% - 5.0% w/v). In the procedure; two different solutions of PLGA in
methylene chloride was prepared. The drug substance, 5-FU, was dissolved in ethanol and were added to the poly-
mer solution. The prepared solutions were stirred for 10 min at 500 rpm; and were spray-dried through a spray-dryer.
The spray-dried microparticles were coated with enteric polymers (Eudragit S 100 and HPMCP HP 55). For this pur-
pose, enteric polymer solutions were prepared by dissolving Eudragit S 100 and HPMCP HP 55 (2:1) into phosphate
buffer (pH 7.4) containing 0.1% Tween 80 at room temperature. 5-FU loaded PLGA microparticles were then dis-
persed in the polymer solution using ultrasonic bath (1 min). The resulting solutions were spray-dried through two
fluid pressurized nozzle of a mini spray dryer. Then, the spray-dried enteric coated PLGA microparticles kept under
vacuum at room temperature. Shape and surface characteristics of the spray-dried microparticles were evaluated by
Scanning Electron Microscopy. Particle size distribution analysis was carried out by a light scattering method using
Malvern Mastersizer, Hydro 2000S, (Malvern Instruments, UK). Zeta potential determination were based on elec-
trophoretic mobility of the microparticles in water and different buffer solutions at pH 2.0, 5.0, 6.8 and 9.0, respec-
tively, using Zetasizer Nanoseries, Nano-ZS, (Malvern Instruments, UK). These measurements were performed at
least in triplicate with independent particle batches. Production yield is expressed as the weight percentage of the
microparticles obtained with respect to the initial amount of polymers and drug used for the preparation. The encap-
sulation efficiency was determined by extracting and quantifying the encapsulated 5-FU using an UV-spectropho-
tometry. Production yields of microparticles obtained with two different concentrations of polymer and drug load-
ing were around 40% (w/w). The produced PLGA microparticles were spherical in shape with slightly porous surface
were observed. The mean particle size of the microparticles was in a range of 14.9 – 30.8 mm with unimodal nar-
row size distribution. A surface charge of the 5-FU loaded microparticles was negative in all measured media. The
encapsulation efficiency was found to be quite high for each formulation, between 65-70% (w/v). The concentration
of the polymer had a positive effect on drug entrapment efficiency, as the concentration increased from 5% to 10%
(w/v), the drug entrapment efficiency increased. This study illustrates a rapid spray-drying method for preparation
of enteric coated PLGA microparticles loaded with 5-FU. The technique was reproducible with high production yield.
Prepared particles were in a micron size range, with a narrow size distribution and high encapsulation efficiency. 
Acknowledgement
The authors would like to acknowledge the support of TUBITAK, (Project Number: 104S076).
Macedonian pharmaceutical bulletin 53 (1,2) 50 (2007)
PP - 6
50
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION