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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.

The treatment of respiratory infections in children requires special attention, since the paediatric population has rather specific characteristics and consists of heterogenous subgroups. In this context, the choice of a suitable drug dosage form is of particular importance, depending on the active substance properties, along with the age and general condition of a paediatric patient. The most commonly used pharmaceutical products for respiratory infections in children include oral, parenteral and inhalation dosage forms, although a large number of drugs are not available in a suitable dosage form and/or strength for paediatric age, leading to the frequent use of unauthorized drugs (i.e., unlicensed use). Other important issues that should be considered when choosing the appropriate paediatric dosage form and/or compounding procedure are related to the careful considerations of the pharmaceutical product composition (safety of excipients) and the choice of administration/dosing device in relation to a child's age. This paper provides an overview of paediatric dosage forms used in the treatment of respiratory infections in children, their benefits and limitations. The review includes examples of various pharmaceutical products, along with the considerations regarding administration/dosing devices. Specific characteristics of paediatric populations affecting the decision on the choice of age-appropriate paediatric formulation are also addressed.

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.

Hot-melt coating (HMC) is an alternative, solvent-free coating method generally used to modify substrate release rate and/or mask its unpleasant taste. The aim of this study was to assess two HMC methods (pan-coating and mortar-coating) by assaying functional properties of the coated material. The selected substrates included highly soluble sodium chloride (model substance) and caffeine (bitter drug), and the coating agent was glycerol distearate without/with the addition of liquid paraffin. Experiments with sodium chloride revealed that pan-coating yielded particles of more regular shape, while mortar-coating yielded samples of more uniform coating layer. The flowability of the coated material depended on the particle size. Sustained sodium chloride release was achieved for all mortar-coated and some pan-coated samples. The analysis of the results indicated mortar-coating as a preferable HMC method for caffeine coating. The resulting caffeine yield in the coated samples was high (99%), the material showed satisfactory mechanical properties and drug release from the coated particles was sustained. Overall, the obtained results suggest that both pan-and mortar-coating can be used to sustain the release of drugs with unpleasant taste, but mortar-coating can be considered as a more simple and practical method that can be potentially used in compounding pharmacies.

The development of solid dosage forms that are both convenient for administration and allow precise drug dosing for pediatric patients is one of the great challenges in contemporary pharmaceutical technology. The presented study has utilized propranolol hydrochloride, as one of the most frequently prescribed drugs that require manipulation of the conventional dosage forms to be administered to children. Multiparticulate oral formulations, powderand granulefilled capsules, as well as mini tablets, were prepared and characterized in terms of their mass and content uniformity and compared to conventional marketed tablets split into halves and quarters. The obtained results have demonstrated the superiority of the multiparticulate formulations, in terms of their average mass and drug content uniformity. It has also been demonstrated that, due to improved flowability, granule-filled capsules are more conveniently compounded and provide higher content uniformity compared to powder-filled capsules. The presented compounding method could be easily employed in community pharmacy settings. Mini tablets with high and uniform content of propranolol hydrochloride have been successfully prepared, thereby presenting a viable strategy for efficient drug dose adjustment.

Computer-based (in silico) modeling & simulation tools have been embraced in different fields of pharmaceutics for a variety of applications. Among these, physiologically-based pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly evaluated over the past few years, as demonstrated by several reports from the pharmaceutical industry, and a number of research and review papers on this subject. Also, the leading regulatory authorities have recently issued guidance on the use of PBPK modeling in formulation design. In silico PBPK models can comprise different dosing routes (oral, intraoral, parenteral, inhalation, ocular, dermal etc.), although the majority of published examples refer to modeling of oral drugs performance. In order to facilitate the use of PBPK modeling tools, a couple of companies have launched commercially available software such as GastroPlus™, Simcyp™ PBPK Simulator and PK-Sim®. This paper highlights various application fields of PBPK/PBBM modeling, along with the basic principles, advantages and limitations of this approach, and provides relevant examples to demonstrate the practical utility of modeling & simulation tools in different stages of formulation development.

The importance of biopharmaceutical considerations in pharmaceutical development and drug characterization has been well recognized both by pharmaceutical industry and regulatory authorities as a tool to establish predictive relationships between drug product quality attributes (in vitro data) and its clinical performance (in vivo data). In the present paper, contemporary biopharmaceutics toolkit including in vivo predictive dissolution testing, Biopharmaceutics Classification System, physiologically based pharmacokinetic and biopharmaceutics modeling and simulation, in vitro-in vivo correlation and biowaiver, are reviewed with regards to relevant general principles and applicability. The recently introduced innovative strategy for patient-centric drug development using an integrated systems approach grounded in fundamental biopharmaceutics concepts, clinical insights and therapeutic drug delivery targets, described as Biopharmaceutics Risk Assessment Roadmap (BioRAM) is also presented. Further development in the field will benefit from joint efforts and exchange of knowledge and experiences between pharmaceutical industry and regulatory authorities for the common goal to accelerate development of effective and safe drug products designed in accordance with patients’ needs and expectations.

Orodispersible dosage forms are intended to be placed on tongue where, in contact with limited saliva volume, fast disintegration, followed by facilitated swallowing, occurred. Intraoral disintegration might be accompanied by drug release and dissolution in oral cavity. Dissolved drug could interact with receptors on taste buds causing taste sensation. The most important critical quality attributes of orodispersible dosage forms are acceptable mechanical resistance, fast disintegration and pleasant taste which have to be monitored and evaluated during formulation development and production. However, compendial methods for orodispersible dosage forms characterization are still lacking, while many authors attempt to develop different, more suitable approaches. The highest variability during determination of disintegration properties is observed. It can be concluded that for the proper disintegration assessment influence of tongue force have to be considered, especially in the case of different polymeric orodispersible films. For reliable development of in vivo study for evaluation of tastemasking efficacy, proper selection and training of panelists accompanied by bitterness threshold determination are of the utmost importance. In order to correlate in vitro and in vivo data, it is necessary to develop analytical method for evaluation of taste-masking efficacy that mimic, in great extent, physiological intraoral conditions.

Depression is the most common mental disorder in the general population and often requires long-term administration of antidepressants. Development of the modified release antidepressant products has led to the lower incidence of the adverse effects and improvement in the adherence, and subsequently to better therapeutic outcomes. Modified release may involve delayed and/or prolonged release of antidepressants. There is an increasing number of marketed antidepressant products in the form of orally dispersible tablets, for the treatment of a particular group of patients with impaired swallowing. Pharmacotherapy of depression in children represents a great challenge due to insufficient data regarding efficacy and safety. Furthermore, in the market of Republic of Serbia, there are no antidepressant products in the age-appropriate dosage forms for pediatric patients. It is, therefore, of great importance to address the risks related to the application of the conventional dosage forms of marketed antidepressants (tablets, hard capsules) to children. Novel treatment options include development of carriers for targeted delivery of antidepressants in the central nervous system. Intranasal administration of antidepressants is particularly favored since it allows the delivery of active ingredients via olfactory and trigeminal nerves. Other transmucosal routes of administration, such as buccal or sublingual, can provide improved therapeutic outcomes, compared to the conventional oral administration, due to circumvention of the intense metabolism of the active ingredients and undesired gastrointestinal side effects.

Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of serious gastrointestinal side effects. Therefore, recent trends in the development of NSAIDs aim to reduce the incidence of side effects, and improve patient compliance. One of the strategies to improve efficacy and safety of oral NSAIDs is the development of combination products that contain gastroprotective agents. Several products containing NSAID in combination with proton pump inhibitors (ketoprofen/omeprazole, naproxen/esomeprazole), H2-receptor antagonists (ibuprofen/famotidine), and prostaglandin analogues (diclofenac/misoprostol) are currently available on the market. Another approach refer to the special formulation design to allow dose reduction while preserving drug therapeutic efficacy. An example is SoluMatrix® technology, a manufacturing process that produce submicron-sized drug particles with enhanced dissolution and absorption properties. Patented SoluMatrix® technology has been successfully employed to develop low-dose diclofenac, meloxicam, indomethacin and naproxen products. Topical NSAID formulations enable drug delivery to target tissues, while reducing systemic exposure and concomitant side effects associated with oral NSAIDs. Dermal/transdermal NSAID delivery systems are subject of intensive investigation. So far, several 'advanced' drug delivery systems with diclofenac, ibuprofen and ketoprofen have been designed.

Conventional granulation methods are associated with significant disadvantages which have led to increased interest and investment in the development of alternative techniques. Melt granulation is an alternative technique with significant potential for the application in production of solid dosage forms. Melt granulation involves the use of binders with relatively low melting point (50 to 100°C) that act as a molten binding liquid in agglomeration process. Considering that solvent is not required, drying phase is avoided, and number of processing steps and costs is reduced in comparison with the traditional wet granulation process. Process is suitable for moisture-sensitive drugs, and by selecting the suitable binder, it can be used to prepare modified or immediate release dosage forms, with improved bioavailability of poorly water soluble drugs, as well as to achieve taste masking. Melt granulation can be performed in the equipment commonly used for wet granulation, such as high shear mixers, fluid bed granulators, and extruders. Numerous formulation variables, process parameters, and equipment-related factors can affect the agglomeration mechanism and characteristics of the granules obtained. Well controlled melt granulation process requires thorough knowledge and understanding of the influence of these factors. Therefore, this research area still requires an intense and often multidisciplinary research.

Achieving wider recognition is part of the development agenda of contemporary cities, which are all confronted with the need to stand out and compete against one another. City branding reads as and plays an important role in this struggle for recognition. The identity of a city is generated over a long period, as it undergoes historical change, resulting in cultural diversity as the product of a specific environment. This paper discusses the possibility of using the cultural and historical heritage of Trebinje and its identity as an asset to create its city brand. Trebinje is a small city situated in the vicinity of Dubrovnik, a major tourist destination with a rich cultural and historical heritage and an excellent city brand. Dubrovnik may be seen as jeopardising the development of Trebinje’s authentic identity; on the other hand, the strong historical ties between the two cities can actually be used as an asset to develop Trebinje’s city brand. The material and non-material heritage which helped the formation of Trebinje’s identity, is analysed. The Mediterranean region in which it is located, its rich history, authentic architecture and different cultural influences, including the national poet Jovan Dučić, have all helped create Trebinje’s genius loci. The same factors may be used to communicate its new image. After that, the paper outlines models of the possible use of the recognised assets to brand the city and emphasise the importance of the effective presentation of these assets for creating a recognisable city image. It also proposes specific actions and interventions that may contribute to branding the city.

This paper considers the possibility of including cultural heritage in cultural and tourist development policies. The tourist potential of historically and artistically significant urban entities will be described and assessed in the paper, with a focus on the cases of Trebinje and Jajce two Bosnian and Herzegovinian towns with preserved historical town cores. The two towns were both founded in the Middle Ages and have developed to this day, with their urban areas continuously expanding and being built up. Their spatial and cultural historical complexes are diverse and multilayered, with various natural and man-made structures dating back to different epochs. They are the greatest cultural monuments and a testimony of the past, of the physical and spiritual development of these communities. Trebinje is an old town located at the intersection of various influences and interests, with a rich and long history which has altered not only the appearance and contents of its town core, but also its significance and its functional impact on the broader surroundings. The Old Town, a surviving historical complex, which originated in the Middle Ages and developed considerably under Turkish rule is one of Trebinje's tourist resources. Nowadays, tourism is becoming one of the world's most important industries, its appeal coming from the natural cultural and historical values of towns and cities. Due to that, the natural cultural and historical values of Trebinje and Jajce can be preserved only if their economic potential is also taken into account.