Patients referred to intensive care units (ICU) require special care due to their life-threatening condition, diseases and, frequently, malnutrition. Critically ill patients manifest a range of typical physiological changes caused by predominantly catabolic reactions in the body. It is necessary to provide the patients with proper nutrition, for example by administering total parenteral nutrition (TPN). The addition of linezolid to TPN mixtures for patients treated for linezolid-sensitive infections may reduce the extent of vascular access handling, resulting in a diminished risk of unwanted catheter-related infections. The compatibility and stability studies were conducted of linezolid in parenteral nutrition mixtures of basic, high- and low-electrolytic, high- and low-energetic and immunomodulatory composition. Mixtures containing linezolid were stored at 4–6 °C and 25 °C with light protection and at 25 °C without light protection for 168 h. In order to evaluate changes in the concentration of linezolid a previously validated reversed-phase HPLC method with UV detection was used. It was found that linezolid was stable at 4–6 °C in the whole course of the study whereas at 25 °C it proved stable over a period of 24 h required for administration of parenteral nutrition mixtures. The TPN mixtures demonstrated compatibility with linezolid and suitable stability, which were not affected by time or storage conditions.
Poor water dissolution of active pharmaceutical ingredients (API) limits the rate of absorption from the gastrointestinal tract. Increasing the pH of a solid form microenvironment can enhance the dissolution of weakly acidic drugs, but data on this phenomenon in a physiologically relevant bicarbonate media are lacking. In this paper, we examined the effect of a microenvironmental pH modulator (Na2HPO4) on the dissolution of a Biopharmaceutics Classification System (BCS) class II free weak acid (ibuprofen) at biorelevant conditions, including an automatic bicarbonate buffering system, as well as in compendial (50 mM) and low-concentration (10 mM) phosphate buffers with no external pH control. The tablets of 200 mg ibuprofen with either Na2HPO4 (phosphate formulation, PF) or NaCl (reference formulation, RF) were manufactured using a compression method. In a pH 2 simulated gastric fluid, only PF produced a transient supersaturation of ibuprofen, dissolving a fourfold higher drug amount than RF. In a bicarbonate-buffered simulated intestinal fluid with a dynamically controlled pH (5.7, 7.2, and 5.8 to 7.7 gradient), PF dissolved more drug within 30 min than RF (p ≤ 0.019). Of note, the use of a 50 mM phosphate buffer pH 7.2 provided opposite results—RF dissolved the API much faster than PF. Moreover, 10 mM phosphate buffers of pH 5.6 and 7.2 could neither maintain a constant pH nor mimic the bicarbonate buffer performance. In conclusion, the use of a bicarbonate-buffered intestinal fluid, instead of phosphate buffers, may be essential in dissolution tests of BCS class II drugs combined with pH modulators. Graphical abstract
Objectives. In geriatric patients, cardiovascular diseases and type 2 diabetes are considered the most common chronic health problems. Moreover, increasing the prevalence of depression, which significantly reduces the quality of life and increases disability in this group, has also been observed. This paper aims to review the literature on the relationship between drugs from selected pharmacological groups used in the treatment of diabetes and cardiovascular diseases and depression, both with respect to their depressive and antidepressant effects. Literature review. The increased risk of the prevalence and the severity of depression is associated with strongly lipophilic beta-blockers and insulin therapy. In contrast, drugs that block the RAA system reduce the risk of developing and worsening symptoms of depression and improve cognitive function in elderly patients. Literature reports indicate the antidepressant effect of commonly used antidiabetic drugs such as metformin and incretin drugs (GLP-1 analogues and DPP-4 inhibitors). The potential anti-depressive effect of intranasal insulin administration requires further research. Conclusions. Based on the review, it should be stated that due to the frequent occurrence of mood disorders in elderly patients, the selection of drugs used in the therapy of somatic diseases should allow for the risk of causing or worsening symptoms of depression. However, the possibility of their beneficial effect on mood disorders should also be considered.
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