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1 350 záznamů v BMČ Filtry

Článek

The impact of glidants on the rheological properties of active pharmaceutical ingredients: A study of conventional and alternative flow enhancers

Verbeek, Tom
Autor Verbeek, Tom Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium Oral Solid Dosage, Drug Product Development, Pharmaceutical Development and Manufacturing Sciences, Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium
De Man, Alexander
Autor De Man, Alexander Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
Van Snick, Bernd
Autor Van Snick, Bernd Oral Solid Dosage, Drug Product Development, Pharmaceutical Development and Manufacturing Sciences, Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium
Otava, Martin
Autor Otava, Martin Janssen-Cilag s.r.o., Janssen Pharmaceutical Companies of Johnson & Johnson, 15800 Prague 5, Czechia
Vervaet, Chris
Autor Vervaet, Chris Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
Vanhoorne, Valérie
Autor Vanhoorne, Valérie Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: valerie.vanhoorne@ugent.be

International journal of pharmaceutics. 2025 ; 671 (-) : 125121. [pub] 20250114

Int J Pharm
ISSN 1873-3476
Medvik
Zdroj

Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs.

Článek online

Mortality of hospitalized patients with COVID-19: Effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) assessed by propensity score matching, retrospective analysis

Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2024 ; 168 (1) : 35-43. [pub] 20231204

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
ISSN 1804-7521
Medvik
Zdroj

INTRODUCTION: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. METHODS: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching. RESULTS: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality. CONCLUSION: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality.

Článek online

Disposition of levobupivacaine during intraoperative continuous caudal epidural analgesia in a preterm neonate

Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2024 ; 168 (1) : 81-84. [pub] 20231122

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
ISSN 1804-7521
Medvik
Zdroj

BACKGROUND: Continuous caudal epidural analgesia used intraoperatively in children is an effective and safe technique. However, in preterm neonates, developmental factors may significantly affect levobupivacaine disposition, leading to variable pharmacokinetics, pharmacodynamics, and potential large-variable systemic toxicity of local anesthetics. OBJECTIVE: To our knowledge, this is the first case report describing the disposition of levobupivacaine used for intraoperative caudal epidural analgesia in a preterm neonate treated for the postoperative pain profile. METHOD: 4-days old neonate (postmenstrual age 35+5, weight 2140 g) with congenital anal atresia received continuous caudal epidural long-term analgesia (loading dose 1.694 mg/kg, initial infusion 0.34 mg/kg/hour) before correction surgery. The blood samples were obtained at 1.0, 1.5, 6.5, 12, and 36.5 h after the start of epidural infusion. The pharmacokinetic profile of levobupivacaine was determined by using the Stochastic Approximation Expectation Maximization algorithm. COMFORT and NIPS pain scores were used for the assessment of epidural analgesia. RESULTS: The levobupivacaine absorption rate constant, apparent volume of distribution, apparent clearance, and elimination half-life were 10.8 h-1, 0.9 L, 0.086 L/h, and 7.3 h, respectively. CONCLUSION: The results confirm our hypothesis of altered pharmacokinetics in the preterm neonate. Therefore, levobupivacaine therapy in these patients should be carefully monitored. Since therapeutic drug monitoring of levobupivacaine is not established in clinical routines, we suggest monitoring the intraoperative pain profile using validated scores. TRIAL REGISTRATION: EudraCT number: 2020-000595-37.