Pulsatile system is gaining a lot of interest as it increases patient compliance by means of providing time and site specific drug delivery system. The aim of the present study was to formulate and evaluate pulsatile drug delivery system of amlodipine besylate based on chronopharmaceutical approach for the treatment of hypertension. The basic design involves the preparation of cross-linked hard gelatin capsules by using formaldehyde. Due to formaldehyde treatment the length, external diameter, thickness, weight of the capsules was increased. Then the drug diluents mixture were prepared and loaded in, which was separated by using hydrogel plugs such as HPMC 50 cP, 100 cP, K100LV, methocel K15, sodium CMC, carbopol 971 and xanthan gum at different amount. Prepared formulations were subjected to in vitro drug release studies. From the in vitro dissolution studies it was found that by increasing the amount of polymer, release rate was decreased. The release rate was above 90% when we used 50 mg and 75 mg polymer (in each hydrogel plug), but in case of using 100 mg polymer the release rate was 70% to 85% in 10 hr. That means, in 12 hr these formulations can give a satisfactory result which is the most desire in pulsatile drug delivery system. Furthermore, the release data of all formulations were fitted to various mathematical models such as zero order, first order, Korsmeyer Peppas, Higuchi and Hixson-Crowell kinetics. The drug release follows mixed order kinetics and mechanism was found to be non-Fickian diffusion. From the result it was concluded that, all formulations showed compliance with chronotherapeutic objective of hypertension and these modified pulsincap formulations can be a best alternative for high blood pressure patient to avoid multiple dosing. However, further studies can be performed to determine the accurate dosing and better therapeutic effect.

Pulsatile system is gaining a lot of interest as it increases patient compliance by means of providing time and site specific drug delivery system. The aim of the present study was to formulate and evaluate pulsatile drug delivery system of amlodipine besylate based on chronopharmaceutical approach for the treatment of hypertension. The basic design involves the preparation of cross-linked hard gelatin capsules by using formaldehyde. Due to formaldehyde treatment the length, external diameter, thickness, weight of the capsules was increased. Then the drug diluents mixture were prepared and loaded in, which was separated by using hydrogel plugs such as HPMC 50 cP, 100 cP, K100LV, methocel K15, sodium CMC, carbopol 971 and xanthan gum at different amount. Prepared formulations were subjected to in vitro drug release studies. From the in vitro dissolution studies it was found that by increasing the amount of polymer, release rate was decreased. The release rate was above 90% when we used 50 mg and 75 mg polymer (in each hydrogel plug), but in case of using 100 mg polymer the release rate was 70% to 85% in 10 hr. That means, in 12 hr these formulations can give a satisfactory result which is the most desire in pulsatile drug delivery system. Furthermore, the release data of all formulations were fitted to various mathematical models such as zero order, first order, Korsmeyer Peppas, Higuchi and Hixson-Crowell kinetics. The drug release follows mixed order kinetics and mechanism was found to be non-Fickian diffusion. From the result it was concluded that, all formulations showed compliance with chronotherapeutic objective of hypertension and these modified pulsincap formulations can be a best alternative for high blood pressure patient to avoid multiple dosing. However, further studies can be performed to determine the accurate dosing and better therapeutic effect.

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Sıçan plazmasında ketiapin ve metabolitleri 7-hidroksi ketiapin ve ketiapin sülfoksit’in tayini için yeni bir yüksek performanslı sıvı kromatografisi yöntemi geliştirilmiş ve valide edilmiştir. Ayrım, C18 kolon (Zorbax Eclipse Plus 4.6 mm x100 mm, 3.5 µm partiküller) üzerinde ve 1 mL/dak akış hızında gradient elüsyon kullanılarak yapılmıştır. Hareketli faz, asetat tamponu (10 mM, pH 5) ve asetonitrilden oluşmaktadır. Analitler DAD dedektör kullanılarak, 225 nm’de saptanmıştır. Tüm analizlerde karbamazepin iç standart olarak kullanılmıştır. Plazma numuneleri, asetonitrille gerçekleştirilen tek basamaklı basit bir protein çöktürme yöntemi sonrasında analiz edilmiştir. Analiz süresi, kolon temizleme basamağını da içerecek şekilde, 15 dakikadır. Yöntem kesinlik, doğruluk, geri kazanım, matriks etkisi ve stabilite parametreleri incelenerek valide edilmiştir. Yöntem ketiapin için 0.065-130 µg/mL aralığında, 7-hidroksi ketiapin için 0.086-171 µg/mL aralığında ve ketiapin sülfoksit için 0.042-83.35 µg/mL aralığında doğrusal bulunmuştur. Tüm validasyon parametreleri kabul edilebilir sınırlar dahilindedir. Bu yöntem, sıçan plazmasındaki analit derişimlerini belirlemek için başarıyla uygulanmıştır.

A new high performance liquid chromatography methodwas developed and validated for the determination of quetiapine and its metabolites 7-hydroxy quetiapine and quetiapine sulfoxide in rat plasma.Separation was performed on a C18 column (Zorbax Eclipse Plus 4.6 mm x100 mm, 3.5 µm particles) using a gradient elution at a flow rate of 1 mL/min. Mobile phase consisted of acetate buffer (10 mM,pH5) and acetonitrile. Analytes weredetected with a DAD detector at 225 nm. Carbamazepine was used as internal standard in all analyses. Plasma samples were analyzed after a simple, one-step protein precipitation with acetonitrile. Separation time was 15 min including clean-up step.The method was validated in terms of precision, accuracy, recoveries, matrixeffect and stability. It was found to be linearin the range of0.065-130 µg/mL for quetiapine,0.086-171 µg/mL for 7-hydroxy quetiapine and 0.042-83.35 µg/mL for quetiapine sulfoxide.All validation parameters were acceptable. This method was successfully applied to quantify the concentrations of the analytes in rat plasma.

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Three toxic plants belonging to Euphorbia genus, namely Euphorbia biumbellata, Euphorbia terracina and Euphorbia dendroides were phytochemically screened and their total phenolic compounds (TPC) and total flavonoid compounds (TFC) were measured and antioxidant capacities were evaluated by DPPH test expressed by Vitamin C Equivalent Antioxidant Capacity (VCEAC). The VCEAC values for the three medicinal plants ranged from 1.0655 g to 0.7285 g of vitamin C equivalents (VCEAC)/100 g of dry matter. The concentrations of TPC and TFC in three plants were respectively 15.13 g to 7.55g of gallic acid equivalents (GAE)/100 g of dry matter and 7.06 g to 5.8 g of quercetin equivalents (QE)/100 g of dry matter. The methanolic extracts of these plants were used to determine their antibacterial activity with the disc diffusion method. The results showed that the three plants were active with the inhibition zones obtained varying from 8 to 22 mm. The highest inhibition zones reached was 22 mm for Euphorbia biumbellata leaves against Staphylococcus aureus. Phytochemical analysis of the total extract showed the presence of biologically active compound groups such as polyphenols, flavonoids, glycosides and tannins.

Three toxic plants belonging to Euphorbia genus, namely Euphorbia biumbellata, Euphorbia terracina and Euphorbia dendroides were phytochemically screened and their total phenolic compounds (TPC) and total flavonoid compounds (TFC) were measured and antioxidant capacities were evaluated by DPPH test expressed by Vitamin C Equivalent Antioxidant Capacity (VCEAC). The VCEAC values for the three medicinal plants ranged from 1.0655 g to 0.7285 g of vitamin C equivalents (VCEAC)/100 g of dry matter. The concentrations of TPC and TFC in three plants were respectively 15.13 g to 7.55g of gallic acid equivalents (GAE)/100 g of dry matter and 7.06 g to 5.8 g of quercetin equivalents (QE)/100 g of dry matter. The methanolic extracts of these plants were used to determine their antibacterial activity with the disc diffusion method. The results showed that the three plants were active with the inhibition zones obtained varying from 8 to 22 mm. The highest inhibition zones reached was 22 mm for Euphorbia biumbellata leaves against Staphylococcus aureus. Phytochemical analysis of the total extract showed the presence of biologically active compound groups such as polyphenols, flavonoids, glycosides and tannins.

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The present simple and sensitive method has been developed for the purpose of bioanalytical study of triamcinolone. The chromatography condition was optimized using a mobile phase 0.5% Tri-Ethyl Amine (TEA) (), pH- 3.48 and acetonitrile in the ratio of 50: 50 at flow rate 1ml/min. and the stationary phase was used as thermo C18 column. The plasma extraction method, protein precipitation technique was achieved 79.5% using 5% of trichloro acetic acid. The drug was eluted at 5.1 min. and no plasma endogenous materials were observed in the retention time. The limit of quantitation (LOQ) of the present method is 100ng/mL and linearity was in the range of 0.5-15.0 μg/mL. The range of drug r2 had shown 0.999. The present successful development and validated method of triamcinolone is shown good accuracy, precision and linearity.

The present simple and sensitive method has been developed for the purpose of bioanalytical study of triamcinolone. The chromatography condition was optimized using a mobile phase 0.5% Tri-Ethyl Amine (TEA) (), pH- 3.48 and acetonitrile in the ratio of 50: 50 at flow rate 1ml/min. and the stationary phase was used as thermo C18 column. The plasma extraction method, protein precipitation technique was achieved 79.5% using 5% of trichloro acetic acid. The drug was eluted at 5.1 min. and no plasma endogenous materials were observed in the retention time. The limit of quantitation (LOQ) of the present method is 100ng/mL and linearity was in the range of 0.5-15.0 μg/mL. The range of drug r2 had shown 0.999. The present successful development and validated method of triamcinolone is shown good accuracy, precision and linearity.

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The purpose of this work was to develop hollow calcium pectinate beads for floating-pulsatile release of ofloxacin intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. A controlled release system designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating drug delivery system by rate controlled drug delivery approach. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic crosslinking. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. The floating beads obtained were porous (38% porosity), hollow with bulk density <1 and had Ft50% of 16–22 h. This approach suggested the use of floating pulsatile dosage forms as they have potential for use as controlled-release drug delivery systems for site and time-specific release of drugs acting as per chronotherapy of diseases.

The purpose of this work was to develop hollow calcium pectinate beads for floating-pulsatile release of ofloxacin intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. A controlled release system designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating drug delivery system by rate controlled drug delivery approach. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic crosslinking. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. The floating beads obtained were porous (38% porosity), hollow with bulk density <1 and had Ft50% of 16–22 h. This approach suggested the use of floating pulsatile dosage forms as they have potential for use as controlled-release drug delivery systems for site and time-specific release of drugs acting as per chronotherapy of diseases.

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Şikimik asit, çeşitli biyolojik aktivitelere sahip ve aynı zamanda, bazı sentetik maddeler için başlangıç materyali olarak dikkat çeken bir fenolik asittir. Bu çalışmada, Alnus glutinosa subsp. glutinosa, A. orientalis var. orientalis ve A. orientalis var. pubescens ile yüksek performanslı sıvı kromatografisi analizleri yapılmış; asetonitril ve %0.2 o-fosforik asit: su karışımı izokratik akış ile mobil faz olarak kullanılmıştır. Akış hızı 0.5 ml/dk olarak verilmiştir. A. glutinosa subsp. glutinosa, A. orientalis var. orientalis ve A. orientalis var. pubescens yapraklarından hazırlanan metanol ekstrelerinde şikimik asit miktarları sırasıyla, %0.6491, %0.4309 ve %0.2452 olarak tespit edilmiştir.

Shikimic acid is a phenolic acid which is known to possess several activities and it takes attention as a leading compound to some synthetic medicinal substances as well. In this study, high performance liquid chromatographic analyses were carried out in order to determine shikimic acid contents of Alnus glutinosa subsp. glutinosa, A. orientalis var. orientalis and A. orientalis var. pubescens; acetonitrile and 0.2% o-phosphoric acid: water mixture with isocratic flow was used as mobile phase. The flow rate was 0.5 ml/min. The quantitative analysis of methanol extracts prepared from the leaves of A. glutinosa subsp. glutinosa, A. orientalis var. orientalis and A. orientalis var. pubescens revealed that shikimic acid amount was found to be 0.6491%, 0.4309% and 0.2452% respectively.

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Bu çalışmanın amacı, Türkiye’den toplanan Pinaceae ve Cupressaceae familyalarına ait bazı türlerin, eterli ekstrelerinin antimikrobiyal aktivitelerinin araştırılmasıdır. Pinaceae familyasına ait olan Pinus nigra Arn., P. brutia Ten., P. halepensis Mill., Abies equi-trojani (Asch. et Sint. ex Boiss.) Coode et Cullen, A. bornmulleriana Mattf., A. cilicica (Ant. et Kotschy) Carr., A. nordmanniana (Steven) Spach., Cedrus libani A. Rich. ve Picea orientalis L. türlerinin ve Cupressaceae familyasına ait olan Juniperus oxycedrus L. subsp. oxycedrus, J. foetidissima Willd., J. excelsa Bieb., J. phoenicea L., Cupressus sempervirens var. pyramidalis Nym. ve C. sempervirens var. horizontalis (Mill.) Gord. türlerinin ekstreleri, Staphylococcus aureus ATCC 25923, S. aureus ATCC 43300 (MRSA), Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae RSKK 574 ve Candida albicans ATCC 10231’a karşı disk difüzyon yöntemi ile araştırılmıştır. A. bornmulleriana, C. libani ve P. halepensis’in test mikroorganizmaları üzerinde antimikrobiyal aktivitesi saptanmazken; diğerlerinin çeşitli bakterilere karşı zayıf antibakteriyel etki gösterdiği ancak C. albicans’a karşı aktivite göstermediği belirlenmiştir. Bu çalışma, bu türlerin eterli ekstrelerinin antimikrobiyal aktivitelerinin değerlendirilmesi üzerine yapılan ilk çalışma olması nedeniyle önem taşımaktadır.

The aim of this study was to determine the antimicrobial activities of ethereal extracts of some Pinaceae and Cupressaceae species collected from Turkey. The extracts from Pinus nigra Arn., P. brutia Ten., P. halepensis Mill., Abies equi-trojani (Asch. et Sint. ex Boiss.) Coode et Cullen, A. bornmulleriana Mattf., A. cilicica (Ant. et Kotschy) Carr., A. nordmanniana (Steven) Spach., Cedrus libani A. Rich. and Picea orientalis L. belong to Pinaceae family and Juniperus oxycedrus L. subsp. oxycedrus, J. foetidissima Willd., J. excelsa Bieb., J. phoenicea L., Cupressus sempervirens var. pyramidalis Nym. and C. sempervirens var. horizontalis (Mill.) Gord. belong to Cupressaceae family were examined against Staphylococcus aureus ATCC 25923, S. aureus ATCC 43300 (MRSA), Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae RSKK 574 and Candida albicans ATCC 10231. The disc diffusion method was used to determine the antimicrobial activities of these extracts. All the tested extracts, except A. bornmulleriana, C. libani and P. halepensis showed weak antibacterial activity against the various tested bacteria comparing with the standards. Nevertheless, no antifungal activity was observed against C. albicans in all extracts. It was concluded that the tested extracts did not show promising antimicrobial activity against tested microorganisms. However, this is the first comprehensive investigation on the evaluation of antimicrobial activities on ethereal extracts of these species.

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The chemical composition of the oleoresin from Daniellia oliveri (Rolfe) Hutch. & Dalz. of the family Caesalpiniaceae was determined using GC-FID/GC-MS and its potentials as antioxidant and cytotoxity evaluated for the first time. The GC-MS analysis revealed the major constituents of the resin as volatile diterpenoids. The major compounds include δ-cadinene (42.92%), copaene (11.36%), cis-muurola-4(14),5-diene (9.56%), polyalthic acid (4.6%), β-calacorene (4.37%), 2(5H)-Furanone-5-(2,5-dimethylphenyl)-4-methyl- (4.35%) and aromadendrene (4.14%). A significant antioxidant activity (IC50= 15.49 ± 0.39 mg/mL) and low cytotoxicity (IC50 > 30 µg/ml) on prostate cancer cell line was obtained for the oleoresin. The low cytotoxicity and moderate antioxidant potential of the oleoresin from D. oliveri is an indication of possible application in related in vivo studies for future therapeutic applications. The major compounds being sesquiterpenes could be used as a biomarker for the chemotaxonomical characterization of the species.

The chemical composition of the oleoresin from Daniellia oliveri (Rolfe) Hutch. & Dalz. of the family Caesalpiniaceae was determined using GC-FID/GC-MS and its potentials as antioxidant and cytotoxity evaluated for the first time. The GC-MS analysis revealed the major constituents of the resin as volatile diterpenoids. The major compounds include δ-cadinene (42.92%), copaene (11.36%), cis-muurola-4(14),5-diene (9.56%), polyalthic acid (4.6%), β-calacorene (4.37%), 2(5H)-Furanone-5-(2,5-dimethylphenyl)-4-methyl- (4.35%) and aromadendrene (4.14%). A significant antioxidant activity (IC50= 15.49 ± 0.39 mg/mL) and low cytotoxicity (IC50 > 30 µg/ml) on prostate cancer cell line was obtained for the oleoresin. The low cytotoxicity and moderate antioxidant potential of the oleoresin from D. oliveri is an indication of possible application in related in vivo studies for future therapeutic applications. The major compounds being sesquiterpenes could be used as a biomarker for the chemotaxonomical characterization of the species.

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Cisplatin yaygın olarak kullanılan etkili bir antikanser ilaçtır. Sağlıklı dokulardaki toksisitesi nedeniyle sisplatinin terapötik kullanımı sınırlıdır. Lipozomlar artan etkililik ve/veya azalan toksisite sağlarlar ve bu sistemler antikanser ilaçların terapötik indekslerini artırmak için potansiyel oluştururlar. Bu çalışmada, cisplatin lipozomları geliştirilmiş ve in vitro karakterizasyonu yapılmıştır. Caco-2 hücre canlılığını belirlemek için sitotoksisite testi yapılmıştır ve sisplatinin IC50 değeri 20 µg/mL olarak bulunmuştur. Sisplatinin diyaliz membrandan salım ve Caco-2 hücresinden geçişi araştırılmıştır. Üç ay boyunca üç farklı sıcaklıkta saklanan lipozomların stabilitesi değerlendirilmiştir. Sisplatin lipozomlarının ortalama partikül büyüklüğü ve zeta potansiyeli yaklaşık 285±0.052 nm ve 2.45±0.65 mV bulunmuştur. Sisplatinin diyaliz membrandan salımı % 53.9±2.71, Caco-2 hücresinden geçişi % 46.2±1.61 olarak elde edilmiştir. Üç ayın sonunda 4ºC’de saklanan lipozomlarda anlamlı partikül büyüklüğü artışı ve zeta potansiyel azalışı gözlenmemiştir (p>0.01). Sonuç olarak sisplatin lipozomları oral yolla kullanılabilir ve tümörlerin tedavisinde olası bir terapötik yaklaşımı temsil etmektedir.

Cisplatin is a potent anticancer drug for treating tumors, that has long been widely used. The therapeutic exploitation of cisplatin is limited by its toxicity toward healthy tissues. Liposomes can provide enhanced efficacy and/or reduced toxicity and these systems offer the potential to enhance the therapeutic index of anticancer agents. In this study, cisplatin liposomes were developed and characterized in vitro. The cytotoxicity test was used to determine Caco-2 cell viability and the IC50 values of free cisplatin was found 20 µg/mL. Release and transport studies of cisplatin through dialyse membrane and Caco-2 cells were investigated. The stability of liposomes was developed when stored at three different temperature for 3 months. The mean particle size and average zeta-potential of the cisplatin liposomes were approximately 285±0.052 nm and 2.45±0.65 mV, respectively. Cisplatin release from dialyse membrane and transport through Caco-2 cells were obtained as 53.9±2.71 % and 46.2±1.61 % respectively. Significant particle size increase and zeta potantial decrease were not observed in cisplatin liposomes after 3 months when stored at 4ºC (p>0.01). Consequently cisplatin liposomes can be delivered orally and represent a potential therapeutic modality in the treatment of tumors.

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Oksidatif stres, reaktif oksijen bileşiklerinin üretimi ile antioksidan savunma sistemlerinin dengesinin bozulmasını tanımlayan bir terimdir. Oksidatif stres, inflamasyon kanser, nörodejeneratif bozukluklar ve kardiyovasküler hastalıklar gibi birçok hastalığın gelişmesinde rol oynamaktadır. Bitkisel fenolik bileşiklerin antioksidan etkili oldukları ve bu nedenle anti kanser etkileri oldukları öne sürülmektedir. Resveratrol (RV), üzüm, fındık, yaban mersini ve ahududu gibi pekçok bitkisel üründe bulunan, doğal olarak oluşan polifenolik bir bileşiktir. RV’nin antioksidan, antiinflamatuvar ve antikanser etkileri olduğu gösteren çalışmalar bulunmaktadır. Ancak RV’nin özellikle kanserin önlenmesinde koruyucu etkilerinin olmadığını da iddia edilmektedir. Bu çalışmada, insan meme adenokarsinoma (MDA-MB 231), insan servikal kanser (HeLa) ve Çin hamster akciğer fibroblast (V79) hücrelerinde RV’nin sitotoksik etkileri, 24 saat inkübasyon sonrasında Nötral Kırmızı Alım (NKA) ve 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) yöntemleri ile değerlendirilmiştir. Her iki sitotoksisite yönteminde de benzer sonuçlar elde edilmiştir. 2-400 µM aralığında, RV’ün tüm hücre tiplerinde belirgin bir sitotoksik etkisi olmadığı görülmüştür. Hatta en yüksek konsatrasyonlarda bile neredeyse hiç sitotoksik etkileri olmamıştır. Bu nedenle IC50 değerleri, bu konsantrasyonaralığında hesaplanamamıştır.

Oxidative stress is the state of imbalance between the level of antioxidant defence system and production of reactive oxygen species (ROS) and is involded in the progression of several diseases such as inflammation, cancer, neurodegenerative disorders and cardiovascular diseases. It is suggested that plant polyphenols may act as antioxidants and therefore it has anti-cancer activities. Resveratrol (RV), is a naturally occuring polyphenolic compound which is found in many plant species including grapes, nuts, blueberries and raspberries. Data indicated that it has anti-oxidant, anti-inflamatory and anti-cancer activities. But there are also some studies reported that RV has not protective effects aganist cancer. In this study, the cytotoxicity of RV in human breast adenocarcinoma (MDA-MB 231), human cervical cancer (HeLa) and Chinese hamster lung fibroblast(V79) cells were evaluated by Neutral Red uptake assay (NRU) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays after incubation at 24 h. We obtained more or the less same results by two cytotoxicity assays. In the concentrations between 2-400 µM, RV seemed not to induce a pronounced cytotoxicity in all cell types. Even at highest concentrations, it showed almost no cytotoxic effects. So the IC50 values were not calculated at the studied concentrations.

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İnhale anti-enfektif ilaçlar, solunum yolu enfeksiyonlarının teşhisinde ve tedavisinde önemli bir rol oynamaktadır. Bu çalışmada, florokinolon grubu bir antibiyotik olan levofloksasin hemihidrat içeren PLGA mikropartikülleri hazırlanmış ve değerlendirilmiştir. PLGA mikropartikülleri su içinde yağ (y/s), su içinde yağ içinde su (s1/y/s2) ve modifiye su içinde yağ içinde su (s1/y/s3) emülsiyon çözücü buharlaştırma yöntemi olmak üzere üç farklı hazırlama yöntemi ile hazırlanmıştır. Hazırlama yöntemlerinin ve formülasyon parametrelerinin mikropartiküllerin partikül büyüklüğü, enkapsülasyon etkinliği, üretim verimi, invitro salım ve aerodinamik özellikleri ile karakterize edilen fizikokimyasal özellikleri üzerine etkileri değerlendirilmiştir. Partikül büyüklüğü sonuçları organik fazda artan diklorometan hacminin partikül büyüklüğünde önemli bir azalmaya neden olduğunu göstermiştir. Tekli emülsiyon yöntemi ile hazırlanan mikropartiküller çoklu emülsiyon yöntemleri ile hazırlanan mikropartiküller ile karşılaştırıldığında daha yüksek enkapsülasyon etkinliği değeri göstermiştir. İn vitro bifazik uzatılmış salım profili elde edilmiştir. F1 kodlu formülasyon dışında hazırlanan tüm formülasyonlar 5 µm’den küçük ortalama kütlesel aerodinamik çapları ile inhalasyon yolu ile uygulanmaya uygundur. Bu sonuçlar levoflokasin hemihidrat içeren PLGA mikropartiküllerinin solunum yolu enfeksiyonlarının levofloksasin ile tedavisi için bir alternatif olabileceğini göstermiştir.

Inhaled anti-infective drugs play a pivotal role in the prophylaxis and treatment of respiratory tract infections. In this study, fluoroquinolone antibiotic levofloxacin hemihydrate-loaded PLGA microparticles were prepared and evaluated. PLGA microparticles were prepared using three different preparation methods such as oil-in-water (o/w), water-in-oil-in-water (w1/o/w2) and modified water-in-oil-in-water (w1/o/w3) emulsion solvent evaporation methods. Effects of preparation methods and formulation parameters on physicochemical properties of microparticles characterized in terms of the particle size, encapsulation efficiency, production yield, in vitro release and aerodynamic properties were evaluated. Particle size results showed that the increasing volume of dichlorometane in the organic phase caused a significant decrease in particle size of microparticles. Microparticles prepared by using o/w emulsion solvent evaporation method showed a higher encapsulation efficiency value compared to those prepared with double emulsion methods. Biphasic extended-release profile was produced in vitro. All formulations prepared except of F1 coded formulation were of suitable aerodynamic size for inhalation having a mass median aerodynamic diameter less than 5 µm. These results showed that levofloxacin hemihydrate-loaded PLGA microparticles could be a potential alternative to the existing levofloxacin therapy in respiratory tract infections.

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