Annales pharmaceutiques francaises最新文献

The coagulation and immune system, both essential physiological systems in the human body, are intricately interconnected and play a critical role in determining the overall health of patients. These systems collaborate via various shared regulatory pathways, such as the Tissue Factor (TF) Pathway. Immunological cells that express TF and generate pro-inflammatory cytokines have the ability to affect coagulation. Conversely, coagulation factors and processes have a reciprocal effect on immunological responses by stimulating immune cells and regulating their functions. These interconnected pathways play a role in both preserving well-being and contributing to a range of pathological disorders. The close relationship between blood clotting and inflammation in the development of vascular disease has become a central focus of clinical study. This research specifically examines the crucial elements of this interaction within the contexts of cardiovascular disease and acute coronary syndrome. Tissue factor, the primary trigger of the extrinsic coagulation pathway, has a crucial function by inducing a proinflammatory reaction through the activation of coagulation factors. This, in turn, initiates coagulation and subsequent cellular signalling pathways. Protease-activated receptors establish the molecular connection between coagulation and inflammation by interacting with activated clotting factors II, X, and VII. Thrombosis, a condition characterised by the formation of blood clots, is the most dreaded consequence of cardiovascular disorders and a leading cause of death globally. Consequently, it poses a significant challenge to healthcare systems. Antithrombotic treatments efficiently target platelets and the coagulation cascade, but they come with the inherent danger of causing bleeding. Furthermore, antithrombotics are unable to fully eliminate thrombotic events, highlighting a treatment deficiency caused by a third mechanism that has not yet been sufficiently addressed, namely inflammation. Understanding these connections may aid in the development of novel approaches to mitigate the harmful mutual exacerbation of inflammation and coagulation. Gaining a comprehensive understanding of the intricate interaction among these systems is crucial for the management of diseases and the creation of efficacious remedies. Through the examination of these prevalent regulatory systems, we can discover novel therapeutic approaches that specifically target these complex illnesses. This paper provides a thorough examination of the reciprocal relationship between the coagulation and immune systems, emphasising its importance in maintaining health and understanding disease processes. This review examines the interplay between inflammation and thrombosis and its role in the development of thrombotic disorders.

Cyclodextrins are enabling pharmaceutical excipients that solubilize and stabilize drugs in aqueous formulations. Cyclodextrins possess very favorable pharmacokinetic and toxicological profiles and are commonly used in marketed drug products for oral and parenteral administration. However, their use in ophthalmic products is still very limited. Cyclodextrins have a broad range of physical properties that are specifically appropriate for designing topical ophthalmic dosage forms. Additionally, both the regulatory and intellectual property environments have been cleared over the last years and should foster their use for designing new drugs for ophthalmic use.

Background: Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration.

Materials and methods: The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41m/z values with significant differences between the drug-treated and control groups (p <0.01 and fold analysis≥1.5).

Results: According to multivariate data analysis, 17-β-estradiol, taurocholic acid, L-kynurenine, N-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5'-methylthioadenosine, L-methionine and S-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways.

Conclusions: The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine.

Objective: The healthcare sector is a paramount and rapidly expanding industry in India. The pharmaceutical field in India has experienced substantial growth and transformation in recent times, making significant contributions to the global healthcare market. This comprehensive review delves into the most recent innovations in pharmaceutical technology transfer (TT), particularly in the context of tablet formulations from an Indian standpoint.

Significance: The pharmaceutical sector has grappled with various challenging issues, including the escalating costs of medications and the demand for patient-friendly products.

Methods: In this technological progress era, various cutting-edge pharmaceutical technologies, such as artificial intelligence (AI), and 3D and 4D printing, play pivotal roles in drug development. Tablets, the most promising and widely utilized dosage form worldwide, require a sophisticated approach to TT. Achieving a successful TT necessitates a dedicated team with well-defined objectives, improved documentation, and effective communication.

Results: The Indian Pharmaceutical Industry (IPI) possesses the potential to make significant contributions to the global healthcare sector. Moreover, we delve into the various phases of TT, highlighting the pivotal role of formulation development and process optimization in ensuring product quality, efficiency, and cost-effectiveness along with different models of TT. Additionally, we examine the challenges associated with TT and potential solutions, as well as the initiatives of the Indian government to bolster the Indian pharmaceutical sector's position as the "Pharmacy of the World".

Conclusion: It is concluded that there is a need to contextualize and institutionalize the tech transfer policies for successful implementation for the benefit of the global population.

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

Objective: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension.

Method: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3237.1.

Result: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation C_max (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet C_max (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax).

Discussion: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.

Objectives: An increased risk of mortality and postoperative side effects led to aprotinin (Trasylol®) withdrawal from the market in 2008, but since 2018 aprotinin has again been used in France. The French retrospective multicentre APACHE study (AProtinin versus tranexamic Acid in Cardiac surgery patients with High-risk for Excessive bleeding) compared the efficacy of tranexamic acid versus half-dose aprotinin. The aim of this study, ancillary to the APACHE study, is to carry out a medico-economic analysis of the use of these two antifibrinolytics on an APACHE subpopulation.

Methods: Economic data on reimbursement by the French health insurance system were extracted from the program for the data processing of medical information, and quantitative data on the cost of healthcare products were obtained from the hospital pharmacy software.

Results: The main analysis of costs for the population shows that the global valuation was not significantly different between the two treatment groups (P=0.60), but the costs of blood products included in the related hospital stay group (Groupe Homogène de séjour [GHS]) (whole blood, platelets and plasma) were higher for the tranexamic acid group (P=0.007). In a sub-analysis of patients alive at discharge, the costs of blood products in addition to GHS (blood-derived medicines) and the costs of blood products in the GHS were higher for the tranexamic acid group (P=0.04 and 0.001, respectively).

Conclusions: The additional cost of aprotinin at the time of purchase is offset by the additional costs of blood products in the tranexamic acid group.

Objectives: An operating room pharmaceutical unit centralizes medical devices and drugs for various surgical specialities. The aim of this work is to present the methodology used in our establishment to set up the operating room pharmaceutical unit.

Methods: This approach involved the formation of multi-professional working groups. The needs of operating theatres were defined based on an analysis of healthcare product consumption and stock inventories. Material sheets were defined for each procedure. On the basis of simulations, material supply arrangements were selected, specifying material flows, equipment, workstations and information systems.

Results: Over 3200 healthcare product references were identified and 862 equipment files were created. Local stocks have been limited to medical trolleys for nursing staff. Emergency operating packs have been deployed for unforeseen operations. Cabinets have been dedicated to transporting re-sterilizable medical devices, and carts have been purchased for programmed operating packs. The equipment is made available by logistics agents and pharmacy assistants under pharmaceutical responsibility.

Conclusions: This innovative approach is a model for facilities desiring to centralize and secure the logistics of healthcare products in the operating room. Ongoing adjustments will be required to meet new operating rooms needs.

Objective: The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside.

Material and method: The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets.

Result: Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm². Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution.

Conclusion: A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

Through their footprint throughout their life cycle, from production to use, medicines have a significant impact on the environment. Reducing this impact is rarely considered from the perspective of the choices that healthcare professionals might have to make when prescribing or dispensing medicines. Should we consider environmental impact, alongside effectiveness and tolerance, one of the dimensions of the proper use of medicines? To address this question, the 5th Forum of the Association for the Proper Use of Medicines highlighted the main sources of pharmaceutical pollution: the carbon footprint linked to production, greenhouse gas emissions, the impact of residues on water and waste from packaging. While the eco-design of medicines should make it possible to limit their environmental impact upstream, there are still few initiatives aimed at their use. The Swedish "Hazard Score" assessment tool, which classifies compounds according to their potential to pollute the aquatic environment, was presented as a tool for guiding prescription choices. Through the exchanges between the various stakeholders (public authorities, doctors, pharmacists, manufacturers, patients) during this forum, recommendations were drawn up both on scientific and ethical grounds.