Evaluation of the permeability and in vitro cytotoxicity of functionalized titanate nanotubes on Caco-2 cell line

Titanate nanotubes (TNTs) are promising vectors for drug delivery due to their unique physicochemical properties such as biocompatibility, mechanical strength, and chemical resistivity. However, considering their strong hydrophilicity, pristine TNTs exert very limited permeability through the intestinal cell layer. The aim of this study was to turn the surface characteristics and thus enhance the permeability of TNTs by functionalization. TNTs were functionalized with trichloro(octyl)silane (TCOS) and magnesium stearate (MgSt). Carbon content and surface free energy of the functionalized TNTs were detected to evaluate the effectiveness of functionalization, by using CHNS analytical and optical contact angle (OCA) measurements, respectively. Caco-2 cell line was applied to test the permeability and the cytotoxicity of the samples. Cytotoxicity was evaluated by using MTT assay. The results revealed that the surface characteristics of TNTs may be adjusted in a wider range with TCOS-TNT than with St, but the samples show higher toxicity. Silane functionalized TNTs may be safe up to 1 mg/ml, while St functionalized TNTs up to 2 mg/ml concentration. The preparation method of MgSt-TNT was also superior from the aspect of environmental safety. The permeability was suitable for samples with moderate hydrophobicity (aqueous contact angle 60-90°).

Patient expectations and regulatory needs in the risk-based drug development of cystic fibrosis

Aims: Cystic Fibrosis (CF) is a rare, chronic, progressive, multi-organ disease. It needs life-long, complex therapy with many difficulties for patients to follow. New therapy development also has difficulties owing to regulatory and economic challenges. Methods: This study evaluates the intervention possibilities of therapy management in CF, taking into consideration the aspects of patient adherence and Quality of Life (QoL), regulatory and economic backgrounds. It presents a Quality by Design (QbD)-based knowledge and Risk Assessment (RA)-based evaluation method. Results: The RA-based evaluation showed that the most highly critical intervention points in the CF therapy-management with greatest positive estimated impact are: increasing of the social support, increasing of the level of patient education and improvement of the potentials of therapy monitoring. The degree of adherence in CF depends mainly on the degree of progression and the complexity of the therapy. New drug combination and new medicine development were found as they have lower critical effect of the patient’s QoL. Conclusion: The risk-based exploration of the therapy interventions can help in finding the factors which have the highest effect on the therapy success and patient adherence. They can be the alternative of a time and cost consuming new medicinal research and development.

The long-term effects of the biolicit procedure for original and biosimilar GCSF and EPO products in Hungary

Aim: We aimed to analyse the long-term effects of the biosimilar bids of NEAK regarding GCSF and EPO drugs. Data and Methods: Our analysis is based on the data derived from the nationwide pharmaceutical database of NEAK. The treatment days and reimbursement figures of 12 months periods has been compared, from 01.07.2011-30.06.2014. and 01.07.2017.-30.06.2019. Results: In the 12 months preceding the price competition bid of biosimilar products 13974 patients received G-CSF, 7.49 billion HUF health insurance reimbursement has been paid, 5 years later the turnover of the product increased (314760, 340100 DOT value), whereas the reimbursement decreased (2.03 billion HUF, 1.95 billion HUF respectively). 12 months before the biosimial price competition, 4167 patients were treated with erythropoietin, resulting in 2.33 billion HUF of reimbursements, in the last 2 years the turnover increased (48727, 50813 DOT value respectively) with decreased reimbursement (1.004 billion HUF, 1.002 billion HUF respectively). Conclusions: The long-range analyses price competition bid of biosimilar products revealed that in case of products the health insurance reimbursement decreased despite the elevated turnover in a longer period as well. During the years following the start of the price competition bid the switch from original products to biosimilars could be observed.

Formulation and investigation of turmeric extract and sodium benzoate loaded capsules

Turmeric has been studied and used as a plant derivate active ingredient for centuries. Several effects of turmeric have been described, however the poor solubility of its active ingredients during the formulation development may limit oral applicability. The aim of research was to involve the development of a dietary supplement of a hard capsule containing turmeric (Curcuma longa) (ground powder from the root standardized to curcuminoid content) and sodium benzoate. The manufacturing technology and the analytic method of the formulation have been developed. Formulation studies according to the Ph. Hg. VIII. standards have been performed. The product may have insulin sensitizing and memory enhancing effects, related animal studies are ongoing.

Overview of the causes and management of drug shortages in the United States and in Hungary

Drug shortages are a multifactorial international concern that is increasingly reported all over the world. A continuously rising number of cases could be observed since 2001, but the issue is particularly significant since 2009. In Hungary, the same increasing tendency was observed; while in 2012 464 shortages occurred, in 2020 1466 cases were reported. According to the Food and Drug Administration, there are three root causes behind the shortages, but several factors can be derived from them. This paper aims at conducting a comprehensive review of literature, exploring these factors in detail and thereby explaining how each of these factors contributes to shortages. Furthermore, it will illustrate how the lack of sufficient information due to an imperfect warning system also contributes to the issue. As the problem affects every stakeholder in the supply chain from patients to Marketing Authorisation Holders, each party should be involved in the development and implementation of mitigating strategies that can provide the basis of policy measures. The article highlights how international trends both in terms of affected therapeutic areas and causes of shortages are reflected in the Hungarian markets; therefore similar approaches could be adapted to tackle the issue domestically and deliver enduring solutions.

Advances in drug release investigations: Trends and developments for dissolution test media

Dissolution research started more than a century ago in the field of physical chemistry and went through several significant developments since. Yet, the explicit attention in drug-related dissolution has only started growing in the 1950s, after the researchers realized that drug release from orally administered solid pharmaceutical formulations significantly influences the bioavailability. Researches show that solubility and permeability of the drugs are key factors in the correlation between the in vitro examination and the in vivo determinations (IVIVC). This review aims to summarize the most relevant developments in chronological order, ranging from simple disintegration studies to biorelevant methods. Biorelevant methods can be used to recognize the effects of food on dissolution, as well as to identify solubility limitations and stability issues. The development of a biologically relevant dissolution method for oral dosage forms needs to take the physiological conditions of the gastrointestinal (GI) tract into account that may influence the drug dissolution. This review presents the simplest dissolution media, the composition of biorelevant media simulating gastrointestinal fluids, and the latest updates of the field.

Non-antibiotic compounds affecting the growth of urinary pathogens during urine culture: a preliminary in vitro study

Introduction: Urine samples are one of the most frequently submitted samples for culture to clinical microbiology laboratories, exceeding the number of most of the other clinical sample types. Various non-antibiotic pharmaceutical compounds may have inhibitory properties on bacteria, as many of these agents accumlate in/eliminated through urine. Methods: Sixty (n=60) pharmacological agents were tested during our experiments. Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603 (ESBL-producing) and Staphylococcus aureus ATCC 29213 were the bacterial strains utilized in this study. Detection of inhibitory activity among the tested compounds was performed on Mueller-Hinton plates, using disk diffusion method. Results: Nineteen (n=19) compounds presented with various levels of inhibitory activity on the tested bacterial strains (four compounds for K. pneumoniae, seven compounds on E. coli and sixteen compounds on S. aureus). The compounds showed the highest levels of inhibitory activity on B. subtilis ATCC 6633, which is one of the main bacterial strains used for the screening of the ’intrinsic’ antibacterial activity of urine. Conclusion: Our results suggest that further experiments, involving additional pharmacological agents is warranted, to establish the full extent of their influence on the appropriate culture of urine samples.

Implementation of Patient Reported Outcome Measures (PROMs) in QbD based formulation development in ophthalmology

Development of drug delivery systems for chronic disorders needs a complex thinking in order to ensure the quality of the product. A multidisciplinary approach of pharmaceutical technology, regulatory and behavioral sciences on the basis of the Quality by Design methodology can be a proper tool for this to handle formulators’, patients’, and also doctors’ needs in therapy planning in case of chronic ophthalmologic disorders. According to the present state-of-the-art”, patient perceptions are collected in the form of the “Patient Reported Outcome Measurements” during the clinical trials, but no feedback is given to the formulation development in order to take these aspects into consideration when designing a new product. This work aims to link the key performance indicators from patients’ point of view to the pharmaceutical development and show a new approach to product development by evaluating the patient and formulator aspect as critical quality attributes within the classical Quality by Design workflow. This study can be the basis of the formulation design and development of a new ophthalmic formulation as it revealed the patient critical needs and requirement.

Spearmint (Mentha spicata L.) essential oil from tipaza (Algeria): in vivo anti-inflammatory and analgesic activities in experimental animal models

Introduction Although analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used to treat a diversity of illnesses, their administration is linked with acute kidney injury and gastrointestinal side effects. The research of new biomolecules and natural products is still needed such as medicinal plants. Aims The present research was aimed to investigate, for the first time, the anti-inflammatory and anti-nociceptive effects of spearmint essential oil (SEO) in mouse models of acute inflammation and pain. Materials and Method Chemical analysis of SEO was done by gas chromatography. The anti-inflammatory activity was tested using two models of acute inflammation namely carrageenan-induced paw edema and xylene-induced ear edema. Histological examination of both non-inflamed and inflamed tissues was evaluated. The anti-nociceptive activity was tested using the pain model induced by acetic acid. Results The main constituent of the SEO was found to be carvone (52.60%). The SEO exhibited a promising anti-inflammatory effect as demonstrated by statistically significant (p<0.05) inhibition of paw volume by 77.24% at the dose of 20 µL/kg and 65.87% at the dose of 200 µL/kg. Furthermore, topical administration of the SEO inhibited xylene-induced ear edema in comparison with the control group (p<0.05). The higher dose (200 µL /kg) significantly (p<0.001) reduced xylene-induced ear edema which was similar to that observed with positive control (ketoprofen). The pathological analysis of the paws and ears revealed that SEO was capable of reducing cellular infiltration and subcutaneous edema. Else, the SEO produced significant anti-nociceptive activity (p<0.001) at higher dose by inhibiting spontaneous nociception. Conclusion These results support the use of SEO in the development of pharmaceuticals for the management of inflammation and pain.

Public knowledge, attitude and practices towards antibiotics and antibiotic resistance: a cross-sectional study in Szeged District, Hungary

The aim of our present study was to assess the knowledge level and attitudes of patients (general population) towards antibiotics and antimicrobial resistance, in addition to their practices towards the procurement and use of these drugs in the Szeged District of Hungary. A cross-sectional, questionnaire-based pilot study was performed among patients aged 18 years or older in the Szeged District. The study population comprised of adult patients attending their general practitioner’s (GP) offices. Data collection for the survey was running between January 2016 and January 2018. Responses from n=109 were included in the final analysis. The median age of the respondents was 51 years (50.8±17.8 years, range: 19-93). The majority of respondents were from the seat of the district and the county (Szeged; n=62; 56.9%). 53.7% (n=59) reported having a chronic illness which requires medical attention/pharmacotherapy. Almost one-third (32.1%) has taken these drugs during the last 12 months. 90.5% (n=99) of respondents has obtained their last course of ABs through a medical prescription. The average number of correct answers overall were 2.11±1.16; highest level of education (p<0.001) and reported use of antibiotics for inappropriate indications showed significant associated in the results of knowledge-based questions (p=0.03). Higher education levels were associated with better knowledge and attitudes, in addition, the majority of respondents were not aware of the differences between bacterial and viral infections and their treatment.