Supercritical fluid technology as a strategy for nifedipine solid dispersions formulation: In vitro and in vivo evaluation.

Supercritical fluid technology (SFT) is an insufficiently investigated approach for the production of solid dispersions, it is environmentally acceptable and has a high potential for application in the pharmaceutical industry. The aim of this work was to formulate and characterize nifedipine solid dispersions (SDs) produced by the SFT and compare the results with ones obtained by the classical solvent based kneading method. The following in vitro tests were conducted: assay and yield, solvent residues, solid state characterization (FTIR, DSC, XRD), flowability, hygroscopicity, solubility, dissolution and stability. Additionally, bioavailability was examined on an animal model (Wistar rats). The formulation selection for in vivo study was performed using the multilevel categoric experimental design and the health risk assessment. Solid state characterization revealed that formulation obtained by the SFT method and higher ratio of polymer (1:5) have had nifedipine in completely amorphous form. Polymer ratio and method of SDs preparation do influence the investigation characteristics. Dissolution rate was fastest in SDs prepared by the SFT and higher polymer ration (1:5). In vivo data of selected SDs prepared by the kneading (ratio 1:1) and the SFT (ratio 1:5) showed alteration in pharmacokinetic profile after i.v. and p.o. application.

Diabetes management, dietary supplements use and the effect of coronavirus pandemic on diabetes patients in Serbia: a cross-sectional study.

OBJECTIVES: Diabetes mellitus (DM) is a significant public health challenge in Serbia, mirroring the situation in other European middle-income countries. The aims of this study were to examine the disease-related characteristics and management of diabetes, as well as the prevalence of use of dietary supplements (DS) among diabetes patients in Serbia, and to analyze the effects of the coronavirus pandemic on DM patients in Serbia. METHODS: The study was carried out as an online, observational, cross-sectional study involving 422 adult diabetes type 1 (DM1) and type 2 (DM2) patients residing in Serbia. RESULTS: DM1 patients were more likely than DM2 patients to self-control glucose levels (p < 0.001). Almost one-third of DM2 patients (31.4%) did not know their HbA1c value. Polypharmacy has been reported by 9.7% of DM1 patients and 23.5% of DM2 patients. During the coronavirus pandemic increased anxiety levels for one-third of respondents was noticed. The prevalence of DS use among DM patients was very high (95.3%), with vitamin C, zinc, vitamin D and magnesium being the most commonly used. Women were more likely to use vitamin D (p = 0.001) and magnesium DS (p = 0.005) than men. Most patients (76.9%) faced limited access to healthcare services during the coronavirus pandemic with, sometimes, detrimental consequences. A significant portion of respondents (41.2%) consulted a pharmacist more often in 2021 than in previous years. CONCLUSIONS: Special caution is needed regarding the potential interactions of DS with chronic therapy. To enhance diabetes care, Serbia needs more accessible mental health support, improved diabetes education, expanded CGM availability, and carefully planned emergency healthcare measures for chronic patients.

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability.

Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work was to examine and compare the characteristics of compounded liquid and solid dosage forms of pantoprazole. Three syrup bases were used: a sugar-free vehicle for oral solution (according to USP43-NF38), a vehicle with glucose and hydroxypropyl cellulose (according to the DAC/NRF2018) and a commercially available SyrSpend Alka base. Lactose monohydrate, microcrystalline cellulose and a commercially available capsule filler (excipient II, composition: pregelatinized corn starch, magnesium stearate, micronized silicon dioxide, micronized talc) were used as diluents in the capsule formulations. Pantoprazole concentration was determined by the usage of the HPLC method. Pharmaceutical technological procedures and microbiological stability measurements were performed according to the recommendations of the EP10. Although dose appropriate compounding with pantoprazole is suitable using both liquid vehicles as well as solid formulations, chemical stability is enhanced in solid formulation. Nevertheless, according to our results, if liquid formulation is a pH adjusted syrup, it could be safely kept in a refrigerator for up to 4 weeks. Additionally, liquid formulations could be readily applied, while solid formulation should be mixed with appropriate vehicles with higher pH values.

The Effect of Humidity on the Dissolution Kinetics and Tablet Properties of Immediate-Release Tablet Formulation Containing Lamotrigine.

This study aims to find the effects of high (75%) and low (30%) humidity conditions and its correlation with formulation composition on dissolution kinetics of lamotrigine (LMT) from prepared immediate-release tablets during one- and four-week periods. Two types of fillers microcrystalline cellulose (MCC) or anhydrous lactose (LAC), disintegrant sodium starch glycolate (NaSG, 0.5% or 4%), and lubricant magnesium stearate (MgST, 0.25% or 5%) were used. A three-factor two-stage complete factorial design (23) was used to assess the influence of the composition of the tested formulations. The tablets were produced by direct compression and characterized using a disintegration test, a resistance to crushing test, and dissolution tests (pH 1.2 and pH 6.8). Using Design Expert software, it was concluded that in addition to the effect of fillers on pH 6.8, NaSG has a significant impact after exposure to high and low humidity, as well as its interaction with LAC and MCC. In the dissolution medium pH 1.2, under conditions of high humidity, the content of MgST and NaSG and their interaction show a significant influence. The release rate of LMT was affected by humidity as well as type of excipients and their interactions.

Pharmaceutical excipients with potential to cause adverse effects in paediatric nasal medicines.

Some pharmaceutical excipients may cause adverse reactions, excipient-related interactions and/or contraindications. Due to the unique characteristics of the paediatric population, adverse effects may occur to substances generally thought safe. The proportion of topical nasal medicines approved for paediatric use and the prevalence and labelling of excipients with known effect (EKE) in these products were compared in Serbia as a non-EU country and Croatia and Slovenia as EU countries. The study was designed as a post-authorization safety study and safety of excipients was considered in accordance with recommendations of the European Medicines Agency (EMA). More than 90% of topical nasal medicines registered in the three countries were approved for paediatric use and more than half of these paediatric medicines contained EKE that may cause adverse effects. Benzalkonium chloride was found in 52.38%, 55.81% and 59.09% of these products in Serbia, Croatia and Slovenia, respectively. Propylene glycol, benzyl alcohol, ethanol, methyl paraben, propyl paraben and boric acid were also present in a few analysed preparations. A significant number of EKE labelling deficiencies were detected in all three countries, hindering healthcare professionals' access to information needed for adequate patient counselling. A revision of the nasal paediatric medicines' PLs and SmPCs is recommended.