Challenges in Patient-Centric Oral Dosage Form Design – the Example of Sumamed

Razvoj oralnih farmaceutskih oblika lijekova po mjeri bolesnika velik je izazov i jedan od glavnih smjerova u području unaprjeđenja oralnih oblika za pedijatrijske i gerijatrijske bolesnike. Djeca i starije odrasle osobe razlikuju se u mnogim aspektima primjene lijeka od drugih dobnih skupina pa trebaju posebna razmatranja čimbenika prihvatljivosti farmaceutskih oblika lijekova koji mogu poboljšati adherenciju i ishode liječenja. Rezultati novijih studija daju dokaze za racionalni razvoj oralnih farmaceutskih oblika lijekova temeljenih na razumijevanju čimbenika prihvatljivosti. Inovativna farmaceutsko-tehnološka rješenja (primjerice, lijek Sumamed u obliku tableta za oralnu suspenziju) zadržavaju prednosti čvrstih farmaceutskih oblika lijekova, a istodobno omogućuju olakšano gutanje kao najvažniju prednost tekućih oblika.Designing patient-centric oral dosage forms is a great challenge and one of the main trends in improving pediatric and geriatric drug delivery strategies. Children and older patients differ in many aspects of medication acceptability from other age groups, thus requiring particular considerations of factors affecting acceptability of dosage forms which can improve the adherence and therapeutic outcomes. The results of recent studies support rational oral dosage form design based on the understanding of factors affecting acceptability. The use of rapidly advancing innovative technologies (such as Sumamed in the form of dispersible tablets) help retain the key advantages of solid dosage forms and at the same time enable easy-to-swallow formulations commonly associated with liquid dosage forms

Challenges in Patient-Centric Oral Dosage Form Design – the Example of Sumamed

Razvoj oralnih farmaceutskih oblika lijekova po mjeri bolesnika velik je izazov i jedan od glavnih smjerova u području unaprjeđenja oralnih oblika za pedijatrijske i gerijatrijske bolesnike. Djeca i starije odrasle osobe razlikuju se u mnogim aspektima primjene lijeka od drugih dobnih skupina pa trebaju posebna razmatranja čimbenika prihvatljivosti farmaceutskih oblika lijekova koji mogu poboljšati adherenciju i ishode liječenja. Rezultati novijih studija daju dokaze za racionalni razvoj oralnih farmaceutskih oblika lijekova temeljenih na razumijevanju čimbenika prihvatljivosti. Inovativna farmaceutsko-tehnološka rješenja (primjerice, lijek Sumamed u obliku tableta za oralnu suspenziju) zadržavaju prednosti čvrstih farmaceutskih oblika lijekova, a istodobno omogućuju olakšano gutanje kao najvažniju prednost tekućih oblika.Designing patient-centric oral dosage forms is a great challenge and one of the main trends in improving pediatric and geriatric drug delivery strategies. Children and older patients differ in many aspects of medication acceptability from other age groups, thus requiring particular considerations of factors affecting acceptability of dosage forms which can improve the adherence and therapeutic outcomes. The results of recent studies support rational oral dosage form design based on the understanding of factors affecting acceptability. The use of rapidly advancing innovative technologies (such as Sumamed in the form of dispersible tablets) help retain the key advantages of solid dosage forms and at the same time enable easy-to-swallow formulations commonly associated with liquid dosage forms

In vitro evaluation of stearylamine cationic nanoemulsions for improved ocular drug delivery

Oil-in-water nanoemulsions (NEs) represent one of the formulation approaches to improve eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is pronounced due to the electrostatic interaction of positively charged droplets with negatively charged mucins present in the tear film, providing prolonged formulation residence at the ocular surface. The aim of this study was to develop a cationic ophthalmic NE with cationic lipid stearylamine (SA) as a carrier of a positive charge. The addition of a nonionic surfactant provided the dual electro-steric stabilization of NEs and enabled tuning of SA concentration to achieve an optimal balance between its interaction with mucins and biocompatibility. Physicochemical characterization, stability profile, in vitro mucoadhesion study and biocompatibility study employing 3D HCE-T cell-based model of corneal epithelium pointed out the NE with 0.05 % (m/m) SA as the leading formulation. Minimizing SA content while retaining droplet/mucin interactions is of great importance for efficacy and safety of future ophthalmic drug products

Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells

BACKGROUND: Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among these nanoparticles, quantum dots (QDs) are highly appealing due to their manipulatable surfaces, yielding multifunctional QDs applicable in different biological models. The biocompatibility of these QDs, however, remains questionable. RESULTS: We show here that QD surface modifications with N-acetylcysteine (NAC) alter QD physical and biological properties. In human neuroblastoma (SH-SY5Y) cells, NAC modified QDs were internalized to a lesser extent and were less cytotoxic than unmodified QDs. Cytotoxicity was correlated with Fas upregulation on the surface of treated cells. Alongside the increased expression of Fas, QD treated cells had increased membrane lipid peroxidation, as measured by the fluorescent BODIPY-C(11 )dye. Moreover, peroxidized lipids were detected at the mitochondrial level, contributing to the impairment of mitochondrial functions as shown by the MTT reduction assay and imaged with confocal microscopy using the fluorescent JC-1 dye. CONCLUSION: QD core and surface compositions, as well as QD stability, all influence nanoparticle internalization and the consequent cytotoxicity. Cadmium telluride QD-induced toxicity involves the upregulation of the Fas receptor and lipid peroxidation, leading to impaired neuroblastoma cell functions. Further improvements of nanoparticles and our understanding of the underlying mechanisms of QD-toxicity are critical for the development of new nanotherapeutics or diagnostics in nano-oncology

Determining Optimal Dry Port Location for Seaport Rijeka Using AHP Decision-Making Methodology

Seaport Rijeka is located and connected to the strategic EU TEN-T transport routes (Mediterranean and Baltic–Adriatic Corridor). Seaport Rijeka represents the shortest connection between Central and Central-Eastern Europe, and overseas destinations, by land and sea, and is in an excellent position to take advantage of its location. Being the largest and busiest seaport in Croatia, with constant increase in cargo traffic, especially container traffic, with inadequate and incomplete transport infrastructure that creates congestion, Seaport Rijeka will soon reach its capacity limits. One of the possible solutions that would satisfy the increasing demand and mitigate existing problems is establishing a dry port. Establishing a dry port serving Seaport Rijeka on the EU transport routes would greatly contribute to the strategic and operational plans of the EU and Croatia. The focus of this paper is to determine the optimal dry port location for Seaport Rijeka. The AHP methodology was used to determine the optimal dry port location of the Seaport Rijeka, by analyzing a large set of influential factors. The analysis was performed for three groups of possible dry port locations (close, medium distance and distant). Results suggest that optimal dry port locations for Seaport Rijeka are in Miklavlje, Velika Gorica and Vinkovci

In vitro dissolution/release methods for mucosal delivery systems

In vitro dissolution/release tests are an indispensable tool in the drug product development, its quality control and the regulatory approval process. Mucosal drug delivery systems are designed to provide both local and systemic drug action following ocular, nasal, oromucosal, vaginal or rectal administration. They exhibit significant differences in formulation design, physicochemical characteristics and drug release properties. Therefore it is not possible to devise a single method which would be suitable for release testing of such versatile and complex dosage forms. Different apparatuses and techniques for in vitro release testing for mucosal delivery systems considering the specific conditions at the administration site are described. In general, compendial apparatuses and methods should be used as a first approach in method development when applicable. However, to assure adequate simulation of conditions in vivo, novel biorelevant in vitro dissolution/release methods should be developed. Equipment set up, the selection of dissolution media and volume, membrane type, agitation speed, temperature, and assay analysis technique need to be carefully defined based on mucosal drug delivery system characteristics. All those parameters depend on the delivery system and physiological conditions at the site of application and may vary in a wide range, which will be discussed in details

In vitro dissolution/release methods for mucosal delivery systems

In vitro dissolution/release tests are an indispensable tool in the drug product development, its quality control and the regulatory approval process. Mucosal drug delivery systems are designed to provide both local and systemic drug action following ocular, nasal, oromucosal, vaginal or rectal administration. They exhibit significant differences in formulation design, physicochemical characteristics and drug release properties. Therefore it is not possible to devise a single method which would be suitable for release testing of such versatile and complex dosage forms. Different apparatuses and techniques for in vitro release testing for mucosal delivery systems considering the specific conditions at the administration site are described. In general, compendial apparatuses and methods should be used as a first approach in method development when applicable. However, to assure adequate simulation of conditions in vivo, novel biorelevant in vitro dissolution/release methods should be developed. Equipment set up, the selection of dissolution media and volume, membrane type, agitation speed, temperature, and assay analysis technique need to be carefully defined based on mucosal drug delivery system characteristics. All those parameters depend on the delivery system and physiological conditions at the site of application and may vary in a wide range, which will be discussed in details

Procena uticaja hidroksipropil guar gume i hijaluronske kiseline na fizičkohemijske i funkcionalne karakteristike oftalmoloških vehikuluma za olopatadin

To improve ocular bioavailability of eye drops, viscosity-increasing polymers with improved functional properties have been used (1,2). The aim of this study was formulation and evaluation of viscous eye drops using vehicles containing hydroxypropyl guar gum (HPG) (0.25% w/v), sodium hyaluronate (SH) (0.4% w/v), and their combination (HPG-SH) as carriers for olopatadine (0.1% w/v). Physicochemical properties (appearance, clarity, pH, osmolality, viscosity) of the prepared formulations were tested. The drug permeability was estimated in vitro using HCE-T cell-based models and the parallel artificial membrane permeability assay (PAMPA). MTT cytotoxicity assay was performed at the end of the permeability study. Physicochemical stability of the formulated eye drops was tested during 12 months. An accelerated stability study was performed using the heating/cooling cycles test. The clarity, pH and osmolality of all formulations were in acceptable range for ophthalmic preparations. Formulation HPG-SH showed significantly higher viscosity (73.1 mPa·s) than formulations with single polymer (7.4 mPa·s for HPG i.e 3.7 mPa·s for SH) pointing to synergistic effect of polymers. The addition of polymers led to a decrease in transcorneal permeability and lower permeability coefficients with prolonged residence of drug at the ocular surface. The results of MTT assay demonstrated that the tested formulations were biocompatible and well tolerated. Formulated eye drops showed satisfactory physicochemical stability under all storage conditions. Olopatadine was successfully formulated in biocompatible viscous ophthalmic solutions. The combination of viscosity enhancer HPG with mucoadhesive polymer SH has a potential to improve precorneal residence time and therapeutic effect of olopatadine.Polimeri poboljšanih funkcionalnih karakteristika koji povećavaju viskozitet koriste se u kapima za oči kako bi se povećala okularna raspoloživost (1,2). Cilj ove studije bio je formulacija i ispitivanje viskoznih kapi za oči korišćenjem vehikuluma koji sadrže hidroksipropil guar gumu (HPG) (0,25% v/v), natrijum hijaluronat (SH) (0,4% v/v) i njihovu kombinaciju (HPG-SH) kao nosača za olopatadin (0,1% v/v). Ispitivane su fizičkohemijske osobine (izgled, bistrina, pH, osmolalnost, viskozitet) pripremljenih formulacija. Permeabilnost leka je procenjena in vitro korišćenjem modela zasnovanih na HCE-T ćelijama i testa permeabilnosti na paralelnim veštačkim membranama (PAMPA). MTT citotoksični test sproveden je na kraju studije permeabilnosti. Fizičkohemijska stabilnost formulisanih kapi za oči ispitivana je tokom 12 meseci. Sprovedena je ubrzana studija stabilnosti korišćenjem cikličnog testa grejanja/hlađenja. Bistrina, pH i osmolalnost svih formulacija bili su u prihvatljivom opsegu za oftalmološke preparate. Formulacija HPG-SH je pokazala značajno viši viskozitet (73,1 mPa·s) od formulacija sa pojedinačnim polimerom (7,4 mPa·s za HPG, tj. 3,7 mPa·s za SH) ukazujući na sinergistički efekat polimera. Dodatak polimera je doveo do smanjenja transkornealne permeabilnosti i nižih koeficijenata permeabilnosti uz produženo zadržavanje leka na površini oka. Rezultati MTT testa su pokazali da su testirane formulacije biokompatibilne i dobro podnošljive. Formulisane kapi za oči imale su zadovoljavajuću fizičkohemijsku stabilnost pri svim uslovima čuvanja. Uspešno su formulisani biokompatibilni viskozni rastvori za oftalmološku primenu sa olopatadinom. Kombinacija HPG kao sredstva za povećanje viskoziteta sa mukoadhezivnim polimerom SH ima potencijal da poboljša prekornealno vreme zadržavanja i terapijski efekat olopatadina.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Ageism and discrimination against the elderly: Discrimination against the elderly in the labor market

U ovom radu govori se o diskriminaciji starijih osoba na tržištu rada i načinima suzbijanja takve diskriminacije. Razjašnjavaju se pojmovi diskriminacija, područja u kojima je zabranjena i koncept ageizma. Sam položaj starijih radnika mijenjao kroz povijest i usko je povezan s demografskim trendovima i promjenama na tržištu rada. Svjetska gospodarska kriza i ubrzan razvoj tehnologija uvelike su utjecali na starije radnike te ih polagano istisnuli s tržišta rada. Također, percepcija javnosti o starijim radnicima je negativna. Prevladavaju stereotipi da su stariji radnici spori, slabijeg zdravlja te nespremni za rad s novim tehnologijama što rezultira diskriminacijom pri samom zapošljavanju. U radu se ističu smjernice za suzbijanje ove vrste diskriminacije, a one prvenstveno obuhvaćaju educiranje i informiranje javnosti i poslodavaca radi promjene negativnih stereotipa o starijim radnicima, osposobljavanje starijih radnika radi usvajanja novih vještina u skladu s potrebama poslodavaca te njihovo aktivno uključivanje u život zajednice. U Republici Hrvatskoj potrebno je više jačati svijest o diskriminaciji starijih osoba te je nužno da nadležna tijela surađuju međusobno te koriste dobru praksu drugih zemalja Europske unije u bavljanju i rješavanju problema diskriminacije.This paper is discussing discrimination against older people in the labor market and ways to deal with such discrimination. Definitions of discrimination, areas where prohibited and the concept of ageism are clarified throughout the paper. The position of older workers through history changes and it is closely related with demographic trends and changes in the labor market. The global economic crisis and the rapid development of technology significantly influence older workers and they are slowly pushed out of the labor market. Also, the public perception of older workers is negative. The prevailing stereotypes of older workers are that they are slow, weaker health and unwilling to work with new technologies which result in discrimination in the hiring process. This paper emphasizes guidelines for dealing with this kind of discrimination and they primarily include educating and informing the public and employers to change negative stereotypes about older workers, training for older workers to acquire new skills to meet the needs of employers and their active involvement in community life. In Croatia, it is necessary to intensify awareness of discrimination against older people and it is essential that the authorities cooperate mutually and use good practices of other countries of the European Union in addressing emerging and solving discrimination problem

Ageism and discrimination against the elderly: Discrimination against the elderly in the labor market

U ovom radu govori se o diskriminaciji starijih osoba na tržištu rada i načinima suzbijanja takve diskriminacije. Razjašnjavaju se pojmovi diskriminacija, područja u kojima je zabranjena i koncept ageizma. Sam položaj starijih radnika mijenjao kroz povijest i usko je povezan s demografskim trendovima i promjenama na tržištu rada. Svjetska gospodarska kriza i ubrzan razvoj tehnologija uvelike su utjecali na starije radnike te ih polagano istisnuli s tržišta rada. Također, percepcija javnosti o starijim radnicima je negativna. Prevladavaju stereotipi da su stariji radnici spori, slabijeg zdravlja te nespremni za rad s novim tehnologijama što rezultira diskriminacijom pri samom zapošljavanju. U radu se ističu smjernice za suzbijanje ove vrste diskriminacije, a one prvenstveno obuhvaćaju educiranje i informiranje javnosti i poslodavaca radi promjene negativnih stereotipa o starijim radnicima, osposobljavanje starijih radnika radi usvajanja novih vještina u skladu s potrebama poslodavaca te njihovo aktivno uključivanje u život zajednice. U Republici Hrvatskoj potrebno je više jačati svijest o diskriminaciji starijih osoba te je nužno da nadležna tijela surađuju međusobno te koriste dobru praksu drugih zemalja Europske unije u bavljanju i rješavanju problema diskriminacije.This paper is discussing discrimination against older people in the labor market and ways to deal with such discrimination. Definitions of discrimination, areas where prohibited and the concept of ageism are clarified throughout the paper. The position of older workers through history changes and it is closely related with demographic trends and changes in the labor market. The global economic crisis and the rapid development of technology significantly influence older workers and they are slowly pushed out of the labor market. Also, the public perception of older workers is negative. The prevailing stereotypes of older workers are that they are slow, weaker health and unwilling to work with new technologies which result in discrimination in the hiring process. This paper emphasizes guidelines for dealing with this kind of discrimination and they primarily include educating and informing the public and employers to change negative stereotypes about older workers, training for older workers to acquire new skills to meet the needs of employers and their active involvement in community life. In Croatia, it is necessary to intensify awareness of discrimination against older people and it is essential that the authorities cooperate mutually and use good practices of other countries of the European Union in addressing emerging and solving discrimination problem