Betahistin dihidroklorürün transdermal amaçlı farklı tipteki formülasyonlarının hazırlanması ve ın vitro-ın vivo değerlendirilmesi

Betahistin Dihidroklorürün Transdermal Amaçlı Farklı Tipteki Formülasyonlarının Hazırlanması ve In Vitro-In Vivo DeğerlendirilmesiBetahistin, vestibüler hastalıkların semptomatik tedavisinde çok yaygın olarak kullanılan bir etkin maddedir. Vertebrobaziler arteriyel sistemde kan akışını artırır, iç kulakta, koklear ve vestibüler sistemlerde mikrodolaşımı düzenler ve yaşlı hastalarda zihinsel fonksiyonları önemli ölçüde geliştirir.Ménière hastalığı gibi periferal dolaşım bozukluklarının eşlik ettiği hastalıklarda, baş dönmesi ve kulak çınlaması gibi durumların sıklığını azaltmada betahistin kullanılmaktadır.İlacın yarı ömrü kısadır ve hızlı eliminasyona bağlı olarak günde üç defa alınması gerekir. Peptik ülser öyküsü olan hastalarda ilacın kontrendike olması, sık alma zorluğu gibi nedenler oral yol dışında başka bir yol arayışını gerektirmektedir.Bu çalışmada betahistinin matriks tipi transdermal sistem formülasyonları hazırlanmıştır. İlacın kontrollü salım sistemi şeklinde verilmesi ile doz aralığı genişleyeceğinden hasta uyuncu artacaktır. Verilecek olan etkin madde miktarının azalmasıyla birlikte yan etkiler de azalacak, fazla ilaç yüklenmesi önlenecektir. Ayrıca, hasta istediği zaman ya da beklenmeyen bir etki görüldüğünde sistemi kolaylıkla deriden uzaklaştırabilecektir.Formülasyonların hazırlanmasında kontrollü ilaç salım sistemlerinin hazırlanmasında yaygın olarak kullanılan Eudragit RL 100 ve Eudragit RS 100 polimerleri kullanılmıştır. Bu iki polimerin farklı oranda karışımları kullanılarak formülasyonlar hazırlanmış ve uygun esneklik kazandıracak plastifiyan seçilerek oranı optimize edilmiştir.Hazırlanan formülasyonlardan betahistinin salım hızı tayini ve insan derisinden ex vivo penetrasyon değerlendirmeleri yapılmıştır. Çalışmanın bir sonraki aşaması ise Wistar sıçanlar ile yapılan in vivo çalışmalardır. İlacın kan konsantrasyonları değerlendirilmiş ve transdermal formülasyonlar ile ilacın en az 12 saat boyunca kanda izlenebildiği sonucuna varılmıştır. Anahtar kelimeler: Betahistin, Eudragit, transdermal terapötik sistem, HPLC analiz yöntemi, insan derisi, Franz hücresi, sıçan, in vivo perkütan absorpsiyon.Preparation and In vitro - In vivo Evaluation of Different Transdermal Formulations of Betahistin Dihydrochloride Betahisine is very extensively used in the symptomatic treatment of vestibular disorders. It increases blood flow in the vertebrobasilar arterial system, improves microcirculation of the internal auditory, cochlear and vestibular systems and significantly improves mental function in elderly patients. Betahistin has been used in the treatment of diseases accompanied by impaired peripheral circulation, e.g. Méniѐre’s syndrome, to reduce the frequency of episodes of vertigo and tinnitus. The drug has a short half-life and should be taken three times daily due to the rapid elimination. Because of the contraindication in patients with peptic ulcer history and the difficulty of frequently dosing requires administration ways other than the oral route.In the study, matrix transdermal system formulations of betahistine were prepared. When the drug is given as controlled release system, dosing time interval will be extended, so the patient compliance will be improved. As the dose amount given to the patient is reduced, adverse effects will be seen less and high amount dose loading will be prevented. Besides, the patient can remove the patch easily in case of an adverse effect or whenever he wants.To prepare the formulations, Eudragit RL 100 and Eudragit RS 100 polymers were preferred which are widely used in controlled release dosage forms. Formulations were prepared using different ratios of these two polymers and a suitable plasticizer and its ratios were optimized.Drug release tests and then, ex-vivo penetration studies from excised human skin were evaluated. The next step of the study is the in-vivo studies which was carried out with Wistar rats. The blood concentrations of the drug were evaluated and as a conclusion, betahistine could be seen at least 12 hours in the blood with transdermal formulations. Key Words: Betahistine, Eudragit, transdermal therapeutic system, HPLC assay method, human skin, Franz diffusion cell, rat, in vivo percutaneous absorption

Preparation and characterization of poly(lactic-co-glycolic acid) nanoparticles containing TGF-beta 1 and evaluation of in vitro wound healing effect

( )Wound healing involves many complex mechanisms, and many growth factors are effective in this process. Growth factors are biologically active polypeptides. They perform activities such as cell growth, differentiation, proliferation and migration with molecular cascades by binding to specific receptors. Transforming growth factor stimulates (TGF-beta) different cell types in the wound healing process. Poly(lactic-co-glycolic acid) (PLGA) degradation produces lactate that expedites angiogenesis, activates pro-collagen factors. Therewith, we hypothesized to combine the therapeutic effect of the TGF-beta 1with the positive effect of the drug delivery system including PLGA nanoparticles (TGF beta-PLGA NP). The burst effect decreases as the polymer concentration increases in PLGA nanoparticles. The inhibitory effect of TGF-beta 1 on keratinocytes was reduced by the improved nanoparticle formulations. It showed a proliferative effect of up to 92.5 per cent on fibroblast cells involved in wound healing. Although TGF-beta 1 has an inhibitory effect on keratinocytes, it induces migration both NIH-3T3 and HaCaT cell lines in the scratch assay

Evaluation of Pharmacy Manager's Knowledge and Attitude on Extemporaneous Preparation

In this work, it is aimed to determine pharmacists' attitude, level of knowledge on extemporaneous formulations including how accurate the formulations are prepared, the problems pharmacists face during preparation, and their approach to solve problems on extemporaneous preparation. Additionally with this work, we aim to gather data on frequently written extemporaneous prescriptions during the recent years. In this work, a questionnaire with the title of Evaluation of pharmacy manager's knowledge and attitude on extemporaneous preparation was applied to pharmacy managers. This questionnaire was completed by 54 community pharmacists. According to our results, it was found that extemporaneous preparations were prescribed to all of the pharmacies that the questionnaire applied, however pharmacists were confronted with various problems during preparation of the formulations

Synthesis and characterization of chitosan-PVA hydrogel containing PEGylated recombinant epidermal growth factor on cell culture for wound healing substitute

The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role