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DOCTORAL DISSERTATION ABSTRACTS…
SST TU UD DIIE ESS O ON N B BIIO OA AD DH HE ESSIIV VE E N NIIC CO OT TIIN NE E D DO OSSA AG GE E FFO OR RM MSS
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Gü üllccaann ‹‹K K‹‹N NC C‹‹
SSuuppeerrvviissoorr:: Prof. Dr. Murat fiumnu, Hacettepe Uni- versity, Faculty of Pharmacy, Department of Phar- maceutical Technology, 06100 S›hh›ye-Anka- ra/TURKEY
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Daattee ooff eexxaam miinnaattiioonn:: January 27, 2003
Buccal permeation of nicotine hydrogen tartrate (NHT) was studied using bovine buccal mucosa at pH 3.6, 7,2 and 8,6. Permeation of NHT across bovine buccal mucosa was increased with the increasing pH. The effect of pH increasing additives (magnesium hydroxide, aluminium hydroxide and calcium carbonate) on the permeation of nicotine was also investigated. Addition of magnesium hydroxide into the donor side increased the permeation of NHT (p<0.05) whereas addition of aluminium hydroxide and calcium carbonate had no significant effect. Adsorpti- on of NHT on the additives was found to be less than 10
%. Buccal adhesive NHT tablet formulations were develo- ped using Carbopol 974 (CP), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium alginate (NaAlg) and chitosan (Protosan 212) at different ratios. In vitro drug release characteristic and bioadhesion of buccal tablets were found to be influenced by the chan- ging type and ratio of polymers. In vivo performance of the buccal tablet containing CP:Protosan 212 at 20:80 ratio was evaluated in 8 healthy volunteers in comparison to a commercially available transdermal nicotine patch (Nico- tinell® TTS 20). Cmax values for transdermal patch and buccal tablets were 12,4±7,1 and 11,7±6,2 ng/mL, and tmax values were 11,5±5,10 and 2,88±0,83 h, AUC values were 204,1±124,9 and 59,3±20,5 ng/mL.h, respectively. No buc- cal mucosal irritation was observed with the tablets whe- reas skin reaction occurred with the transdermal patch only in one volunteer. As the same plasma level was ob- tained with the developed buccal tablet formulation in a shorter period of time when compared to the transdermal patch, the buccal tablet seems to be a suitable system for acute nicotine replacement.
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Keeyy WWoorrddss:: Nicotine hydrogen tartrate, pH increasing additive, buccal permeation, bioadhesive tablet, absorption
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DE ESSIIG GN N A AN ND D E EV VA AL LU UA AT TIIO ON N O OFF M MIIT TO O-- X
XA AN NT TR RO ON NE E L LO OA AD DE ED D M MIIC CR RO OP PA AR RT T‹‹C CU UL LA AT TE E SSY YSST TE EM MSS FFO OR R T TH HE E T TR RE EA AT TM ME EN NT T O OFF B BR RA AIIN N T TU U-- M
MO OR RSS
SSiibbeell B BO OZ ZD DA A⁄ ⁄ P PE EH HL L‹‹V VA AN N SSuuppeerrvviissoorr:: Prof.Dr. Y›lmaz Çapan,
Hacettepe University, Faculty of Pharmacy, Depart- ment of Pharmaceutical Technology, 06100 Ankara- Turkey
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Daattee ooff E Exxaam miinnaattiioonn:: February 18, 2003
A significant limiting factor in treating malignant glioma is the inability to deliver therapeutic concentrations of chemotherapeutic drugs to the tumor without incurring unacceptable systemic side effects. Implantable, biodegra- dable polymers provide a useful and practicle means of maximizing the efficacy of antineoplastic drugs by provi- ding vehicles for local and sustained drug delivery di- rectly to the tumor. For this reason, in this study, mito- xantrone, an antitumour drug of the antitumour antibi- otic classification, encapsulated in chitosan, albumin and PLGA microspheres were prepared for the treatment of malignant gliomas, and microspheres were tested in vitro for the particle size, yield, drug loading, surface morpho- logy and release characteristics. As a result of morpholo- gical evaluation by SEM for all the formulations, MTZ-lo- aded microspheres were spherical in shape and they had a smooth surface structure. The amount of MTZ released from chitosan and albumin microspheres decreased with increasing cross-linking densities. RG2 cells and HL-60 cells were tested for cytotoxicity to mitoxantrone-loaded albumin microspheres in the MTT test. As a result of this study, mitoxantrone-loaded albumin microspheres sho- wed the most growth inhibiting effect on RG2 cells and HL-60 cells.
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Keeyy WWoorrddss:: Microsphere, chitosan, albumin, PLGA, mi- toxantrone, malignant glioma, MTT test, RG2 cell line, HL-60 cell line.
DOCTORAL DISSERTATION ABSTRACTS
60 FFO OR RM MU UL LA AT TIIO ON N A AN ND D IIN N V VIIT TR RO O / / IIN N V VIIV VO O E EV VA A--
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LU UA AT TIIO ON N O OFF T TO OP PIIC CA AL L SSO OL LIID D L LIIP PIID D P PA AR RT TIIC CL LE ESS Y
Yoonnccaa Y YA AZ ZIIK KSSIIZ Z ‹‹fifiC CA AN N
SSuuppeerrvviissoorr:: Prof. Dr. Süeda Hekimo¤lu, Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 S›hhiye-Ankara/
TURKEY.
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Daattee ooff eexxaam miinnaattiioonn:: February 20, 2003
DEET (N,N-diethyl-m-toluamid) is an insect repellent that has a widespread use. It is generally used in alcoholic so- lutions and it is well known that, long-term use of DEET causes not only skin irritation but also systemic side ef- fects when it is used in high concentrations. In this study, DEET was incorporated into solid lipid particles, a collo- idal drug delivery system, that are being used in topical applications in order to reduce the percutaneous perme- ation and to avoid toxic effects and also to maintain drug effectiveness on the skin surface for a long duration of in- sect repellency. Three different techniques were used in the preparation of the formulations. Following the charac- terization studies, the lyophilized formulation with the highest loading capacity which contains 20 % lipid phase and 1:1 drug:lipid ratio was carried to in vitro release and skin permeation studies. Solid lipid particles with DEET in different vehicles were compared to free DEET. Results showed that incorporation of DEET into solid lipid partic- les reduced skin permeation. Imaging studies using scan- ning electron microscopy showed that solid lipid particles could remain up to two hours on the skin surface. In order to evaluate skin irritancy, monolayer cell lines were used and solid lipid particles with and without DEET were fo- und to be cytotoxic in high concentrations. In vivo studies were performed by measuring blood flow and erythema of the skin in order to determine skin irritancy. DEET in- corporated into solid lipid particles that were applied in different vehicles were found to be less irritant when com- pared to free DEET. As a result, incorporation of DEET in- to solid lipid particles reduced both percutaneous perme- ation and in vivo irritation potential of DEET.
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Keeyy WWoorrddss:: DEET, solid lipid particles, controlled rele- ase, skin penetration, skin irritation, in vivo skin bioengineering.
