OBJECTIVE To examine the influence of vehicles on the stability of extemporaneous suspensions of proton pump inhibitors (PPIs), to single out the formulation most suitable for children, providing appropriate evidence and arguments. METHODS A review was performed of data identified from Medline, Embase, Science Direct, as well as public digital archive PubMed, including reference texts, related to the field of stability testing of extemporaneous PPI suspensions. RESULTS Fourteen selected formulations of extemporaneous suspensions are presented and discussed. Depending on the vehicle and its composition, which was analyzed and explained in detail, the suspensions had various beyond-use dates (BUDs). CONCLUSIONS Selected vehicles and the process of preparation had great influence on the stability of extemporaneous PPI suspensions. The suspension with the longest BUD has been singled out, which is especially suitable for use in newborns. Because an explanation is provided for the influence of individual vehicle components on the stability of the mentioned suspensions, this can aid not only in the selection of an adequate formulation, but also in the development of new ones, which will be suited to individual patients.

Microneedles (MNs) represent the concept of attractive, minimally invasive puncture devices of micron-sized dimensions that penetrate the skin painlessly and thus facilitate the transdermal administration of a wide range of active substances. MNs have been manufactured by a variety of production technologies, from a range of materials, but most of these manufacturing methods are time-consuming and expensive for screening new designs and making any modifications. Additive manufacturing (AM) has become one of the most revolutionary tools in the pharmaceutical field, with its unique ability to manufacture personalized dosage forms and patient-specific medical devices such as MNs. This review aims to summarize various 3D printing technologies that can produce MNs from digital models in a single step, including a survey on their benefits and drawbacks. In addition, this paper highlights current research in the field of 3D printed MN-assisted transdermal drug delivery systems and analyzes parameters affecting the mechanical properties of 3D printed MNs. The current regulatory framework associated with 3D printed MNs as well as different methods for the analysis and evaluation of 3D printed MN properties are outlined.

© Author(s) (or their employer(s)) 2021. No commercial reuse. See rights and permissions. Published by BMJ. We come from Bosnia and Herzegovina, a small country in western Balkans. Our Faculty of Pharmacy at the University of Sarajevo was opened in 1973, but from then on there was no kind of online teaching. So when the COVID-19 pandemic broke out, and when the university decided to stop all kinds of ‘inclass’ teaching (12 March 2020), we were faced with something new. We work at the Department of Pharmaceutical Technology, where we teach regular courses on ‘Drug Formulation’ and ‘Industrial Pharmacy’. Students take classes in these subjects in the seventh, eighth and ninth semesters. The exercises are practical and last several hours. On 25 March 2020, classes in the lecture hall were suspended until further notice by the decision of the Senate of the University of Sarajevo, and then we realised that we must embark on the adventure of organising online classes. We carried out short research on available online teaching platforms to find basic information on the platform’s capabilities, identify their advantages and disadvantages, and check their commercial prices. We studied the following platforms for online courses: Google Meet, Adobe Connect, Zoom and BigBlueButton, and the following platforms for online examinations: Exam. net, Virtualx, Google Forms, Skillsbook, Papershala, Edbase, Kaldin and TCExam. After examining the possibilities of the available online teaching platforms, we agreed that Zoom and Google Meet provide the best results for running online courses. Adobe Connect, Blackboard Collaborate and BigBlueButton work on the same principle, but professional versions of these platforms were quite unaffordable to us. The results for the online examination platforms are summarised in table 1. Given the security and price of the platforms, we concluded that Exam. net currently meets our criteria, but that it would be necessary to use two platforms simultaneously during the examination, one of which would allow an established video connection with students during the examination (eg, a combination of Exam. net and Zoom). Students accessed the examination platform from their laptop while simultaneously established a video connection with the teacher on their mobile device. At the end of the semester, we conducted an online survey in which 60 (70.93%) of 86 students participated, and for 98.4% of the students this was their first online learning experience. Although it is assumed that current students (digital natives) have adequate information and communications technology competence, they differ in their computer and information literacy as they come from different socioeconomic backgrounds. Of the students, 21.3% had technical difficulties (ie, unstable connection). One of them said she/he has problems with misunderstanding from parents who required help with housework at the time of the lecture because she/he comes from the countryside. Of the students, 75% were satisfied with the conducted online classes at our department. Onethird found it easier to follow theoretical lectures online. Here are some comments from the students:

Microneedles (MNs) have been manufactured using a variety of methods from a range of materials, but most of them are expensive and time-consuming for screening new designs and making any modifications. Therefore, stereolithography (SLA) has emerged as a promising approach for MN fabrication due to its numerous advantages, including simplicity, low cost, and the ability to manufacture complex geometrical products at any time, including modifications to the original designs. This work aimed to print MNs using SLA technology and investigate the effects of post-printing curing conditions on the mechanical properties of 3D-printed MNs. Solid MNs were designed using CAD software and printed with grey resin (Formlabs, UK) using Form 3 printer (Formlabs, UK). MNs dimensions were 1.2 × 0.4 × 0.05 mm, arranged in 6 rows and 6 columns on a 10 × 10 mm baseplate. MNs were then immersed in an isopropyl alcohol bath to remove unpolymerized resin residues and cured in a UV-A heated chamber (Formlabs, UK). In total, nine samples were taken for each combination of curing temperature (35°C, 50°C, and 70°C) and curing time (5 min, 20 min, and 60 min). Fracture tests were conducted using a hardness apparatus TB24 (Erweka, Germany). MNs were placed on the moving probe of the machine and compressed until fracture. The optimization of the SLA process parameters for improving the strength of MNs was performed using the Taguchi method. The design of experiments was carried out based on the Taguchi L9 orthogonal array. Experimental results showed that the curing temperature has a significant influence on MN strength improvements. Improvement of the MN strength can be achieved by increasing the curing temperature and curing time.

Although homeostasis is a commonly accepted concept, there is incontrovertible evidence that biological processes and functions are variable and that variability occurs in cycles. In order to explain and understand dysregulation, which has not been embraced by homeostatic principles, the allostatic model has emerged as the first serious challenge to homeostasis, going beyond its homeostatic roots. Circadian rhythm is the predominant variation in the body, and it is a pattern according to which many physiological and pathological events occur. As there is strong experimental and clinical evidence that blood pressure fluctuations undergo circadian rhythm, there is equally strong evidence that targeted time therapy for hypertension provides a better outcome of the disease. The research has gone even further throughout the development and approval process for the use of pulsatile drug release systems, which can be considered as an option for an even more convenient dosage regimen of the medicines needed.

Since glaucoma is a serious health problem, numerous therapeutics are being developed to reduce Intraocular Pressure (IOP) as the only modifiable factor of all glaucoma symptoms. IOP-lowering agents are divided into six groups, each of which has a specific mechanism of action and side effects, which are the focus of this article and are explained in detail. All the mentioned agents are formulated as eye drops. However, as conventional topical eye drops have significant disadvantages, of which poor bioavailability and patient noncompliance are the main, novel approaches to designing their drug delivery systems were used and briefly presented in this review. Review Article Rahić et al.; OR, 14(2): 17-33, 2021; Article no.OR.66197 18 Graphical Abstract

As physical permeation enhancers, microneedles (MNs) can modificate stratum corneum by creating microchannels, that are large enough to enable drugs, including macromolecules, to enter the skin while being small enough to avoid pain, irritation, and needle phobia [1,2]. Great emphasis is placed on the production process of microneedles itself, the selection of the most suitable materials as well as their shape, density, and size. This work aimed to fabricate biodegradable PLA MNs using additive manufacturing, more precisely fused deposition modeling (FDM) technology, and investigate the effect of varying geometry and print settings on the printed MNs in order to develop microneedles of optimal shape, density, and height. Ultimaker 5S 3D printer (Ultimaker, Netherlands) was used to print triangular and cylindrical MNs with different heights (0,6 mm, 1,2 mm, and 1,8 mm) and different number and orientation of single arrays on the base (5x5, 3x3, 1x5) using 2.85 mm PLA filament (3D Republika, Serbia). The results showed the ability of Ultimaker 5S to successfully print MNs with different shapes, where the triangular shape was chosen to be more acceptable for transdermal delivery. 1.8 mm height was chosen as the optimal height for the MNs, while the 5 x 5 orientation of single arrays on the base resulted in more accurately printed MNs without a lot of waste material between the needles. Based on the results obtained, it can be concluded that FDM printing parameters can easily be adjusted to develop MNs of optimal shape, density, and height for transdermal drug delivery.

MicroRNA-based medicines have drawn attention as a promising tool for the treatment of various diseases. Due to the poor biomembrane permeation, cellular uptake, and enzymatic instability of naked microRNA, the clinical success of gene therapy is mostly dependent on formulating efficient and safe transfection vectors [1]. Therefore, we aimed to develop cationic solid lipid nanoparticles (SLN) for gene therapy purposes. SLN containing 0.15% of stearylamine, 4.85% of Precirol ATO 5 (solid lipid), 1% of Tween 80, and 1% of Poloxamer 188, as non-ionic surfactants, were produced using a high-pressure homogenization process (800 bar and three cycles). microRNA 27-a was further complexed with SLN in the following SLN/microRNA ratios: 1:5, 1:2.5, 1:1, 2.5:1, 5:1, 10:1, 25:1 and characterized using dynamic light scattering, electrophoretic light scattering, and gel retardation assay. The SLN had a mean diameter of 112 ± 0.5 nm (PDI of 0.202 ± 0.011) and a zeta potential (ZP) value of +30.6 ± 1.25 mV. Complexation of SLNs with microRNA decreased a particle size from 244.8 ± 2.7 to 120.4 ± 0.4 nm with an increasing weight ratio of SLNs, while the biggest particle size was observed in 1:1 ratio (1146 ± 110.2 nm) due to low ZP values (3.45 ± 0.2 mV). Further, ZP increased from -14.3 ± 0.4 mV to + 39.7 ± 0.5 mV. Both ELS data and gel retardation assay results revealed that complete complexation could be attained above the weight ratio of 5:1. Our investigations suggest that SLN poses a high potential to be non-viral gene carriers in miRNA replacement therapy.

Glaucoma is considered to be one of the biggest health problems in the world. It is the main cause of preventable blindness due to its asymptomatic nature in the early stages on the one hand and patients’ non-adherence on the other. There are several approaches in glaucoma treatment, whereby this has to be individually designed for each patient. The first-line treatment is medication therapy. However, taking into account numerous disadvantages of conventional ophthalmic dosage forms, intensive work has been carried out on the development of novel drug delivery systems for glaucoma. This review aims to provide an overview of formulation solutions and strategies in the development of in situ gel systems, nanosystems, ocular inserts, contact lenses, collagen corneal shields, ocular implants, microneedles, and iontophoretic devices. The results of studies confirming the effectiveness of the aforementioned drug delivery systems were also briefly presented.

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).