INTRODUCTION: The aim of this study was to evaluate the tableting performance of starches when used in combination either as a disintegrant or binder in tablet formulation.
METHODS: Metronidazole granules were prepared by wet granulation incorporating either maize starch, potato starch or a combination of the two starches as binder or disintegrant at 10 % w/w. The granules were evaluated for their physicochemical properties and compressed into tablets weighing approximately 400 mg following the addition of extragranular excipients. The tablets were kept for 24 h to allow for elastic recovery and the properties of weight, drug content, thickness, tensile strength, friability, disintegration, and dissolution studies were evaluated for each tablet formulation.
RESULTS: The results shows that granule properties did not differ significantly across the formulations irrespective of the type and combination of starches used in the formulation either as binder or disintegrant. However, it was observed that there were slight differences in mean granule size, bulk and tapped densities of granule formulations containing the combined starch as excipients. Tablets prepared using the combined starches as binder had lower tensile strength and disintegration time when compared to other formulations incorporating the individual starches as binders. However, when evaluated as disintegrant, the tablet formulation containing the combined starches produced tablets with relatively lower disintegration time when compared to formulations containing the individual starches as disintegrant.
DISCUSSION AND CONCLUSION: Hence, the combination of maize and potato starches as excipients in tablet formulation influenced the outcome of granule and tablet properties.

INTRODUCTION: The aim of the investigation is to prepare sustained release pellets of diltiazem hydrochloride employing almond gum and gelucire. The study was performed to explore the suitability of almond gum in the preparation of pellets of diltiazem hydrochloride without the use of microcrystalline cellulose and role and effectiveness of hydrophobic gelucire (43/01) in controlling the drug release.
METHODS: Pellets were prepared by extrusion–spheronization of the blend previously obtained by incorporation of the drug in a mixture of melted Gelucire 43/01 and almond gum. A 3² factorial design was employed to study the effect two independent variables, almond gum and gelucire on the size, friability and drug release from pellets. Scanning electron microscopy, differential scanning calorimetry and infra-red spectroscopy were performed to characterize pellets

RESULTS: Free flowing spherical pellets could be prepared. The 3² factorial study revealed that as the proportion of almond gum increased, the size of pellets increased while increasing gelucire had opposite effect. The yield of pellets prepared in different formulations is in the range of 86 to 92 %. The size of pellets varied from 1128 to 1458 µ. Higher amounts of gelucire resulted in pellets with more friability whereas increasing the amount of almond gum yielded pellets with low friability. The pellets exhibited sustained release of diltiazem and the presence of gelucire in the matrix of the pellets had an enhanced sustaining effect on release.
DISCUSSION AND CONCLUSION: Dispersion of the drug in gelucire before it is converted to pellets resulted in extended release of drug. The drug release rate changed with changes in the proportion of pellet composition. The results of the study suggest that employing gelucire (43/01) in the preparation of pellets is a useful approach in the design of sustained release products of highly water soluble drug such as diltiazem hydrochloride.

INTRODUCTION: Software systems are commonly used by professionals to assist identification of drug interactions and to ensure the safe use of medications. Real-world evidence about the comparison of different drug interaction sources is scarce. Objective: To compare two drug interaction databases used to identify interactions in a population-based survey.
METHODS: This is a cross-sectional study based on a previous survey performed in the city of Manaus, Brazil, in 2019. We included adults aged 18 years and over who used two or more medicines 15 days prior to the interview. In order to assess potential drug interactions, we searched Micromedex and UpToDate databases. The primary outcome was the prevalence of potential drug interactions in each database. Weighted Kappa statistics was calculated to assess agreement on the presence of drug interaction, documentation and severity.
RESULTS: A total of 752 participants were included in the study. The prevalence of drug interactions was 43.8% (95% CI: 40.2, 47.3%) in UpToDate and 30.2% (95% CI: 26.9, 33.5%) in Micromedex. The agreement related to drug interactions between the two databases was fair (Kappa=0.631). For r severity (Kappa=0.398) and documentation (Kappa=0.311), the agreement was poor.
DISCUSSION AND CONCLUSION: Agreement among compared databases was sub-optimal. Better quality and transparency on evidence available in drug interaction sources are needed to support informed health care professionals’ decision.

GİRİŞ ve AMAÇ: İnterferonlar (IFN), özellikle influenza virüsleri gibi RNA genomlarını taşıyan virüslere karşı doğuştan gelen bağışıklığın en önemli bileşenlerinden biridir Viral enfeksiyon esnasında, interferonlar hızla salgılanır, hedef hücrelerde birçok genin ekspresyonunu indükler ve antiviral bir durum oluşturur. Bu çalışmada, interferon ile ilişkili bazı genler tarafından kodlanan proteinlerin influenza A virüsü RNA bağımlı RNA polimeraz (RdRP) enzimi üzerindeki etkileri araştırıldı. Bu proteinlerin farklı influenza A virüs tiplerinin patogenezindeki önemi değerlendirildi.
YÖNTEM ve GEREÇLER: İnterferonla ilişkili genler, HEK293 cDNA kitaplığından PCR ile çoğaltıldı ve pCHA memeli ekspresyon vektörüne klonlandı. Genlerin ekspresyonu Western blotlama ve proteinlerin hücredeki lokalizasyonları immünofloresan boyama ile belirlendi. İnterferonlarla ilişkili proteinlerin virüs RdRP enzimi üzerindeki etkileri influenza A virüsü mini-replikonları deneyleri ile belirlendi.
BULGULAR: Çalışma, influenza A virüsü enfeksiyonlarının, HEK293 hücrelerinde interferonla ilişkili CCL5, IFIT1, IFIT3, IFITM3 ve OAS1 genlerinin transkript seviyesini önemli ölçüde değiştirdiğini ortaya koydu. Gen ekspresyonundaki değişikliğin virüs tipi ile de ilişkili olduğu belirlendi. Mini-replikon deneylerinde, CCL5, IFI27, OAS1, IFITM3, IFIT1 ve IFIT3'ün geçici ekspresyonunun hem WSN hem de DkPen tipi virüs RdRP enzimleri üzerinde inhibitör etkileri olduğunu göstermiştir. OAS1 dışındaki proteinlerin WSN tipi RdRP enzimini DkPen enziminden daha yüksek düzeyde inhibe ettiği gözlendi.
TARTIŞMA ve SONUÇ: İnfluenza A virüsü enfeksiyonunun, konakçı hücrelerde interferonla ilişkili gen ekspresyonunu önemli ölçüde değiştirdiği sonucuna varılmıştır. Bu genlerden kodlanan proteinlerin çoğu, HEK293 hücrelerinde virüs RdRP enzimleri üzerinde inhibitör etki göstermiştir. İnfluenza virüsü RdRP'nin interferonla ilgili proteinlerle inhibisyonu, konakçı protein ve viral enzim alt birimleri arasındaki doğrudan veya dolaylı etkileşimlerin sonucu olabilir.

INTRODUCTION: Interferons (IFNs) are one of the most important components of innate immunity against viruses especially those carrying the RNA genomes such as influenza viruses. Upon viral infection, the IFNs are rapidly secreted, inducing the expression of several genes in the target cells and establishing an antiviral state. In this study, the effects of proteins encoded by some interferon-related genes on influenza A virus RNA dependent RNA polymerase enzyme were investigated. The importance of these proteins in the pathogenesis of different influenza A virus types was evaluated.
METHODS: The interferon-related genes were amplified by PCR from the HEK293 cDNA library and cloned into pCHA expression vector. The expression of genes and subcellular localizations of the proteins were determined by Western blotting and immunofluorescence staining, respectively. The effects of interferons-related proteins on virus RdRP enzyme were determined with influenza A virus mini-replicons.
RESULTS: The study revealed that the influenza A virus infections significantly altered the transcript level of the interferon-related CCL5, IFIT1, IFIT3, IFITM3, and OAS1 genes in HEK293 cells. It was determined that the alteration of the gene expression was also related to the virus type. The mini-replicon assays showed that the transient expression of CCL5, IFI27, OAS1, IFITM3, IFIT1, and IFIT3 have inhibitory effects on WSN and/or DkPen type virus RdRP enzymes. It was observed that the proteins except OAS1 inhibited WSN type RdRP enzyme at a higher level than that of DkPen enzyme.
DISCUSSION AND CONCLUSION: It was concluded that influenza A virus infection significantly alters the interferon-related gene expression in the cells. Most of the proteins encoded from these genes showed an inhibitory effects on the virus RdRP enzymes in the HEK293 cells. The inhibition of the influenza virus RdRP with interferon-related proteins may be the result of direct or indirect interactions between the host proteins and the viral enzyme subunits.

GİRİŞ ve AMAÇ: Bir NDDS olarak transdermal ilaç dağıtımı, kontrollü ilaç salınımı ve geliştirilmiş hasta uyumu için bilim adamlarının büyük bir araştırma ilgisi haline geldi. Bu çalışma, uygun miktarda uygun polimerler kullanılarak optimize edilmiş bir Tramadol hidroklorür transdermal yaması geliştirmek için gerçekleştirilmiştir. Ayrıca, sürekli salım modeli elde etmek için cihazdan ilaç geçirgenlik oranının kontrol edilmesi de planlandı.
YÖNTEM ve GEREÇLER: Yardımcı maddelerin miktarı değiştirilerek birkaç formülasyon hazırlanmıştır. İstenen özelliklere sahip optimize edilmiş formülasyonu elde etmek için fizikokimyasal ve biyofarmasötik parametreler kontrol edildi.
BULGULAR: FT-IR sonuçları anormal tepe noktaları göstermedi ve dolayısıyla ilaç ve polimerlerin birbiriyle uyumlu olduğu sonucuna vardı. Farklı fizikokimyasal parametrelerin minimum SD değerleri, hazırlama yönteminin en az parti içi değişkenlik ile yamaları formüle etme becerisine sahip olmasını sağlamıştır. HPMC'nin daha yüksek yüzdesi, yamaların daha yüksek gerilme mukavemeti, nem içeriği ve su buharı iletim hızı ile sonuçlanmıştır. Yüksek katlanma dayanıklılık değeri (>200), hazırlanan yamaların esnekliğini ve cilde bütünlüğünü gösterir. Yalnızca HPMC polimeri içeren F26 olarak kodlanan transdermal yamalar, ex-vivo geçirgenlik çalışmaları yoluyla 12 saat içinde istenen ilaç geçirgenlik oranını (%65.51) göstermiştir.
TARTIŞMA ve SONUÇ: F26 olarak kodlanan formülasyonun, aynı zamanda formülasyonun matris tipi ilaç iletimi sergileme kabiliyetini de doğrulayan higuchi difüzyon kinetiğinin ardından sürekli bir şekilde ilaç geçirgenlik oranını sergilediği için en optimize edilmiş yama olduğu bulundu.

INTRODUCTION: Transdermal drug delivery as a novel drug delivery system (NDDS) has become a major research interest to the scientists for its controlled drug release and improved patient compliance. This work was carried out to develop an optimized transdermal patch of Tramadol hydrochloride using appropriate amount of suitable polymers. It was also planned to control the drug permeation rate from the device to achieve sustained release pattern.
METHODS: Several number of formulations were prepared altering the amount of excipients. Physicochemical and biopharmaceutical parameters were checked to get the optimized formulation with desired characteristics.
RESULTS: Fourier transform infrared (FT-IR) spectroscopy results displayed no abnormal peaks and hence concluded that drug and polymers were compatible with each other. Minimum standard deviation (SD) values of different physicochemical parameters assured that the method of preparation was skilled to formulate patches with least intra batch variability. Higher percentage of hydroxypropyl methylcellulose (HPMC) resulted in the greater tensile strength, moisture content and water vapor transmission rate of the patches. High folding endurance value (>200) indicated about the flexibility of the prepared patches and their integrity to the skin. The transdermal patches coded as F26 containing only HPMC polymer demonstrated the desired drug permeation rate (65.51%) within 12 hour through ex-vivo permeation studies.
DISCUSSION AND CONCLUSION: The formulation coded as F26 was found to be the most optimized patch as exhibited its drug permeation rate in a sustained manner following higuchi diffusion kinetics that also confirmed about the capability of the formulation to exhibit matrix type drug delivery.

There are several blood-based markers to assess iron stores, but they all have some limitations. Hepcidin, a low-molecular-weight peptide hormone, is mainly produced by liver. It is the main regulator of iron homeostasis through prevention iron release into plasma from absorptive enterocytes and macrophages. The objective of this review is to critically assess existing data on potential role of hepcidin in diagnosis, particularly the (pre) analytical implications of the hepcidin measurement. There is a well-known causative correlation between hepcidin and iron deficiency. Therefore, hepcidin is considered to be a promising marker in the assessment of iron status, particularly in patients with diagnostic dilemma, such as patients with chronic renal disease and infants. The clinical implications of this peptide hormone in diagnosis of other diseases have been expanded in the recent studies, including elevated hepcidin levels in neoplastic diseases, sepsis and inflammation. The potential role of hepcidin in diagnosis is controversial in the various types of iron deficiency because data is conflicting (as in anaemia of chronic disease) or limited (as in infants), whereas in the case of hereditary haemochromatosis, it has been proposed that hepcidin may be used for stratification of molecular testing, or to improve the frequency of phlebotomy, however this issue still needs to be investigated. Due to lack of a clinically approved test, the medical application of this peptide as a biomarker in diagnosis is restricted. Recently, assays have been developed to determine hepcidin levels in serum and urine, facilitating the future use of hepcidin in research and clinical practice.

Kozmetiklerin yan etkilere neden olmadığı düşünülse de araştırmalar, önemli sayıda tüketicinin yan etkilere maruz kaldığını ortaya koymuştur. Kozmetik ürünlerin kullanımından kaynaklanan istenmeyen etkiler, ürünün içeriğinde yer alan maddelerin kullanımına ilişkin bazı kısıtlamalardan ve kozmetik düzenlemelerin yürürlüğe girmesini sağlayan, raporlama ve değerlendirmeye dayanan kozmetovijilans sistemini gerekli kılmıştır.
Ancak yeni kozmetovijilans konseptinin halk sağlığı açısından daha etkili olabilmesi için bazı güncellemelere ihtiyacı vardır. Örneğin, kozmetiklerin kullanımına bağlı yan etkiler son yıllarda daha sık bildirilse de bu oran hala oldukça düşüktür. Ayrıca mevcut kozmetik direktifi kozmesötikleri kozmetikten ayrı bir kategori olarak tanımadığından, kanunlarda kozmetik olarak adlandırılan bazı ürünler epidermisin alt katmanlarını etkileyerek sistemik yan etkilere neden olabilmektedir. Üreticilerin lisans alabilmek için güvenlik değerlendirmelerini Türkiye İlaç ve Tıbbi Cihaz Kurumu(TİTCK)’na göstermeleri gerekse de, piyasaya sürdükten sonra sistemdeki bir diğer sorun olan kuruma teyakkuz sonrası raporlama yapmamalarıdır.
Bu derlemede, Türkiye'deki mevcut kozmetovijilans sistemini ele alınmistir ve kozmetovijilans sisteminin uygulanmasında karşılaşılan bazı zorluklar eleştirilmistir. Ayrıca kozmetik içeriklerinde yan etkilere neden olabilecek ve gelişen kozmetovijilans kavramına katkı sağlayan bilimsel çalışmaları derlenmiştir.
Sonuç olarak, sağlık profesyonellerinin kozmetovijilans sistemindeki geri bildirimlerinin önemi, tüketiciye verilecek danışmanlık hizmeti ve hastaya dikkat edilmesi gereken içerikler hakkında bilgi verilmiştir. Ayrıca Türkiye pazarında kozmetiklere bağlı advers reaksiyon insidansını gösteren yeni çalışmalara ihtiyaç vardır. Bu derleme makalesinin bir diğer sonucu da kozmetik pazarında yeni etken maddelerin artışına yönelik yeni düzenlemelerin öneminin anlaşılmasıdır.

Although it is thought that cosmetics do not cause side effects, studies have revealed that a significant number of consumers experience side effects. Undesirable effects arising from the use of cosmetic products have created the need for reporting and evaluation system which is responsible for some restrictions on the use of cosmetics ingredients and putting into cosmetic regulations effect, called cosmetovigilance.
However, the new cosmetovigilance concept needs some updates to become more effective for public health. For instance, side effects related to cosmetic use have been reported more frequently in recent years, but this rate is still quite low. In addition, since the current cosmetic directive does not recognize cosmeceuticals as a distinct category from cosmetics, some products named cosmetic under the laws may affect the bottom layers of dermis and cause systemic side effects. Although the manufacturers must show safety assessments to Turkish Pharmaceutical and Medical Device Agency (TITCK) to get a license, after launching they do not have post-vigilance reporting to the institution which is another problem of the system.
In this review, the current cosmetovigilance system in Turkey was discussed and some hardships encountering were criticized regarding the implementation of the system. In addition, scientific studies are compiled on cosmetic ingredients that can cause side effects and contribute to the developing cosmetovigilance concept.
As a result of the study, the importance of the feedback of healthcare professionals in the cosmetovigilance system, the consultancy service to be given to the consumer and the patient about the contents that should be considered. Besides, there is a need for new studies to indicate the adverse reaction incidence related to cosmetics in the Turkish market. Another outcome of this review article is to understand the importance of the new regulations regarding the increase of the new active ingredients in the cosmetic market.