{"title":"An overview on the application of supercritical carbon dioxide for the processing of pharmaceuticals","authors":"S. Milovanović, I. Lukić","doi":"10.5937/arhfarm72-39999","DOIUrl":"https://doi.org/10.5937/arhfarm72-39999","url":null,"abstract":"Supercritical carbon dioxide (scCO2) application in the pharmaceutical industry is still undeveloped regardless of significant research interests in this processing medium shown in the last decades. ScCO2 technologies can improve drug solubility, bioavailability, and therapeutic effect. These technologies can lead to the development of new formulations that will contribute to a decrease in drug dose, medication frequency, and increase patients' well-being. Considering the significant decrease in the price of high-pressure equipment and society's growing need for cleaner production and safer products, it is expected that symbiosis between supercritical fluid and pharmaceutical technologies will happen soon. Therefore, this review was focused on the latest contributions of scCO2 technologies to the pharmaceutical field. The main aim was to bring these technologies closer to pharmaceutical specialists. For this purpose, the most commonly used technologies were explained and discussed: the preparation of solid dispersions, polymer impregnation with drugs, and drug micro/nanoparticle production using scCO2.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Đuričić, V. Todorović, Nevena Dabetić, Milica Zrnić-Ćirić, N. Ivanovic, B. Vidović
{"title":"Dietary factors and thyroid dysfunction","authors":"I. Đuričić, V. Todorović, Nevena Dabetić, Milica Zrnić-Ćirić, N. Ivanovic, B. Vidović","doi":"10.5937/arhfarm72-39624","DOIUrl":"https://doi.org/10.5937/arhfarm72-39624","url":null,"abstract":"Besides iodine deficiency, autoimmune Hashimoto thyroiditis is the leading cause of hypothyroidism globally, characterized by the increased titer of thyroid autoantibodies and destruction of thyroid cells. Graves' disease is the most common etiology of hyperthyroidism worldwide. Patients with thyroid dysfunction often require dietary modifications. Popular interventions include supplementation with certain vitamins and minerals, as well as trace elements such as iodine and selenium. The intake of food containing goitrogens should be limited. Goitrogens are substances of plant origin that interfere with the production of thyroid hormones, increasing the risk for goiter and hypothyroidism. The primary dietary sources of goitrogens are cruciferous vegetables, soy products, starchy plants, and some fruits. Beyond essential nutrients, there has been an increasing interest in using specific nutraceuticals, including myoinositol, Lcarnitine, melatonin, and resveratrol, as potential preventive and therapeutic agents in thyroid diseases. Even though current evidence promotes some beneficial outcomes of these nutraceuticals, further investigations are needed to clarify dose-dependent effects, duration of supplementation, combination in different clinical settings, and the exact mechanism of their action in thyroid disorders.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Aleksić, Teodora Glišić, S. Cvijić, J. Parojčić
{"title":"Liquisolid systems: Evaluation of the influence of formulation variables on the optimum liquid load","authors":"I. Aleksić, Teodora Glišić, S. Cvijić, J. Parojčić","doi":"10.5937/arhfarm72-33130","DOIUrl":"https://doi.org/10.5937/arhfarm72-33130","url":null,"abstract":"Liquisolid systems represent an emerging approach in the preparation of solid dosage forms with liquid lipophilic drug or poorly water-soluble drug solution/suspension in suitable liquid vehicle. This study addresses the lack of data regarding the compaction behavior of liquisolid systems, with the aim to investigate the influence of liquid load, carrier to coating ratio, carrier type (microcrystalline cellulose vs. spray dried calcium hydrogen phosphate, anhydrous (Fujicalin®)) on flowability and compaction properties of liquisolid systems and to determine the optimum liquid loads. Liquisolid admixtures with Fujicalin® showed notably better flowability than those with microcrystalline cellulose. An increase in carrier to coating ratio led to enhanced flowability of the admixtures. Compacts with Fujicalin® had good mechanical properties up to 24.7% liquid, while those with microcrystalline cellulose had acceptable mechanical strength up to 16.2% liquid. Liquisolid systems with Fujicalin® showed similar tabletability profiles as those with microcrystalline cellulose, despite having higher liquid content. The ejection stress values indicated that the addition of lubricant might be needed in the case of liquisolid systems with Fujicalin®. Superior properties of Fujicalin® as a carrier for liquisolid tablets were revealed, and dynamic compaction analysis was found to be a valuable tool for the assessment of compaction behavior of liquisolid systems.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid nanoparticles employed in mRNA-based COVID-19 vaccines: An overview of materials and processes used for development and production","authors":"I. Pantelić, T. Ilić, I. Nikolić, S. Savić","doi":"10.5937/arhfarm72-33660","DOIUrl":"https://doi.org/10.5937/arhfarm72-33660","url":null,"abstract":"In the light of the recommended application of the third dose, both public and professional community would benefit from a detailed report on the technological advances behind the developed messenger ribonucleic acid (mRNA) based COVID-19 vaccines. Although many vaccine developers are yet to reveal their precise formulations, it is apparent they are founded on nanotechnology platforms similar to the one successfully used for registered drug OnpattroTM (INN: patisiran). Optimal encapsulation of mRNA requires the presence of four lipids: an ionizable cationic lipid, a polyethylene-glycol (PEG)-lipid, a neutral phospholipid and cholesterol. Together with other excipients (mainly buffers, osmolytes and cryoprotectives), they enable the formation of lipid nanoparticles (LNPs) using rapid-mixing microfluidic or T-junction systems. However, some limitations of thermostability testing protocols, coupled with the companies' more or less cautious approach to predicting vaccine stability, led to rigorous storage conditions: -15° to -25°C or even -60° to -80°C. Nevertheless, some inventors recently announced their mRNA-LNP based vaccine candidates to be stable at both 25° and 37°C for a week. Within the formulation design space, further optimization of the ionizable lipids should be expected, especially in the direction of increasing their branching and optimizing pKa values, ultimately leading to the second generation of mRNA-LNP COVID-19 vaccines.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivana Adamov, Đorđe Medarević, B. Ivković, A. Ivković, S. Ibrić
{"title":"Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: The concept of a combined polypill","authors":"Ivana Adamov, Đorđe Medarević, B. Ivković, A. Ivković, S. Ibrić","doi":"10.5937/arhfarm72-40365","DOIUrl":"https://doi.org/10.5937/arhfarm72-40365","url":null,"abstract":"Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of 8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were successfully printed, as well as combined two-layered 3D tablets, with each of the active substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs from the combined two-layered 3D tablets was observed. The absence of drug-polymer interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further optimization of formulation factors is necessary to achieve complete drug release.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jelena Đuriš, Jovana Pilović, Marina Džunić, S. Cvijić, S. Ibrić
{"title":"Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products' qualitative composition","authors":"Jelena Đuriš, Jovana Pilović, Marina Džunić, S. Cvijić, S. Ibrić","doi":"10.5937/arhfarm72-40397","DOIUrl":"https://doi.org/10.5937/arhfarm72-40397","url":null,"abstract":"Text mining (TM) applications in the field of biomedicine are gaining great interest. TM tools can facilitate formulation development by analyzing textual information from patent databases, scientific articles, summary of products characteristics, etc. The aim of this study was to utilize TM tools to perform qualitative analysis of paracetamol (PAR) and ibuprofen (IBU) formulations, in terms of identifying and evaluating the presence of excipients specific to the active pharmaceutical ingredient (API) and/or dosage form. A total of 152 products were analyzed. Web-scraping was used to retrieve the data, and Python-based open-source software Orange 3.31.1 was used for TM and statistical analysis (ANOVA) of the obtained results. The majority of marketed products for both APIs were tablets. The predominant excipients in all tablet formulations were povidone, starch, microcrystalline cellulose and hypromellose. Povidone, stearic acid, potassium sorbate, maize starch and pregelatinized starch occurred more frequently in PAR tablets. On the other hand, titanium dioxide, lactose, shellac, sucrose and ammonium hydroxide were specific to IBU tablets. PAR oral suspensions more frequently contained dispersible cellulose; liquid sorbitol; methyl and propyl parahydroxybenzoate, glycerol and acesulfame potassium. Specific excipients in other PAR dosage forms, such as effervescent tablets, hard capsules, oral powders, solutions and suspensions, as well as IBU gels and soft capsules, were also evaluated.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivana Vasiljević, Erna Turković, I. Aleksić, J. Parojčić
{"title":"Mathematical approaches for powders and multiparticulate units processability characterization in pharmaceutical development","authors":"Ivana Vasiljević, Erna Turković, I. Aleksić, J. Parojčić","doi":"10.5937/arhfarm72-40961","DOIUrl":"https://doi.org/10.5937/arhfarm72-40961","url":null,"abstract":"An understanding of material properties and processing effects on solid dosage forms performance is required within the Quality-by-design approach to pharmaceutical development. Several research groups have developed mathematical approaches aiming to facilitate the selection of formulation composition and the manufacturing technology. These approaches are based on material particulate, bulk and compression-related properties. This paper provides theoretical assumptions and a critical review of different mathematical approaches for processability characterization of powders and multiparticulate units. Mathematical approaches have mainly been developed for directly compressible materials, but sometimes other manufacturing technologies, such as roller compaction and wet granulation, are also considered. The obtained compact tensile strength has been implemented in the majority of approaches, as an important characteristic describing compact mechanical properties. Flowability should be also evaluated, since it affects sample processability. Additionally, particle size and shape, material density and compressibility, compactibility and tabletability profiles have been also distinguished as relevant properties for solid dosage form development. The application of mathematical approaches may contribute to the mechanistic understanding of critical material attributes and facilitate dosage form development and optimization. However, it is essential to select the appropriate one, based on the intended dosage form characteristics, in order to ensure that all relevant powder/multiparticulate units characteristics are implemented and critically evaluated.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liquisolid systems as a novel approach in formulation and manufacturing of solid dosage forms: Challenges and perspectives","authors":"I. Aleksić, Teodora Glišić, J. Parojčić","doi":"10.5937/arhfarm72-40329","DOIUrl":"https://doi.org/10.5937/arhfarm72-40329","url":null,"abstract":"Liquisolid systems are a novel, promising platform for the production of solid dosage forms with a high liquid content, i.e. dispersion of the drug in a suitable, hydrophilic, non-volatile liquid vehicle or liquid drug. This technology requires conventional, but highly porous excipients (carrier and coating material in the appropriate ratio) able to absorb/adsorb liquid medication, resulting in both good flowability and acceptable compression properties. This approach has shown great potential to improve the dissolution rate and bioavailability of poorly soluble drugs, and has been recognized as a good alternative to common, more complex and expensive techniques. A variety of applications of this simple technique have been investigated recently, including the preparation of: modified release tablets, orally disintegrating tablets, solid dosage forms with liquid herbal extracts, etc. This emerging technology has numerous advantages, and the most important are: simplicity, cost-effectiveness, applicability in large scale production and environmental friendliness. However, it is accompanied by certain challenges as well, such as limited applicability in the case of highly dosed drugs. This article aims to give a comprehensive overview of recent progress regarding the potential applications of this technology, as well as to give an insight into the new liquisolid-based techniques intending to further support its commercial applicability.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Jeremić, F. Milosavljević, A. Opanković, M. Jukic
{"title":"Patients' and psychiatrists' stance on the current state of pharmacological depression treatment in Serbia and prospects of introduction of personalized pharmacotherapy and its potential effects","authors":"A. Jeremić, F. Milosavljević, A. Opanković, M. Jukic","doi":"10.5937/arhfarm72-37613","DOIUrl":"https://doi.org/10.5937/arhfarm72-37613","url":null,"abstract":"The use of antidepressants has been steadily increasing. Even though the amount of evidence on the usefulness of personalized drug dosing in depression treatment is growing, there is still resistance and skepticism among physicians and regulators regarding the implementation of CYP450 genotyping and therapeutic drug monitoring in psychiatric clinical practice. The aim of this study was to quantify the opinions of psychiatrists and patients from three large psychiatric clinics in Belgrade, Serbia, and to examine what requirements need to be met to make changes in clinical guidelines or recommendations. All participants completed an anonymous questionnaire that was developed at the Faculty of Pharmacy, University of Belgrade. Fourteen practicing psychiatrists and 30 patients currently treated for depression completed the questionnaire. Distributions of opinion scores were compared between the psychiatrists and patients upon the visual inspection of the violin plots. Our results show that psychiatrists predominantly have a positive opinion on personalized dosing in psychiatry and that patients are most likely to comply with new approaches in depression pharmacotherapy. However, due to the long time needed for regulatory change, it is very unlikely that personalized dosing would be rapidly implemented in clinical practice, even if adequate evidence was to emerge.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71198929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medications and non-pharmacological measures to alleviate the symptoms of respiratory tract infections in the pediatric population","authors":"M. Tomić, Uroš Pecikoza","doi":"10.5937/arhfarm72-38025","DOIUrl":"https://doi.org/10.5937/arhfarm72-38025","url":null,"abstract":"In the pediatric population, acute respiratory tract infections (RTIs) are the most common reason for seeking professional help from a physician or a pharmacist. Alleviation of symptoms is the only therapeutic measure in viral RTIs and is an adjunct to antibiotic therapy in bacterial RTIs. This article discusses pharmacologic and nonpharmacologic options for treating nasal congestion, cough, fever and sore throat in RTIs and clinical evidence on their efficacy and safety in the pediatric population. In general, clinical studies conducted in children for most of these drug groups are few or nonexistent, making it difficult to create evidence-based recommendations. Nasal decongestants, cough suppressants, mucolytics, expectorants, antipyretics/analgesics and sore throat local preparations are available in suitable pharmaceutical forms and strengths for the certain age. As many of them are over-the-counter (OTC) preparations, it is necessary to strictly take into account the age of the child in whom they may be used and dose properly. Multicomponent preparations carry the risk of taking unnecessary medications and of their side effects. The use of multiple OTC medicines is associated with the risk of an overdose of a component that may be present in different preparations. Appropriate non-pharmacological measures (e.g. oral hydration, nasal saline application or irrigation, honey) may be helpful and should be used whenever possible due to their safety.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}