Dissolution of a Biopharmaceutics Classification System Class II Free Acid from Immediate Release Tablets Containing a Microenvironmental pH Modulator: Comparison of a Biorelevant Bicarbonate Buffering System with Phosphate Buffers.

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.

Evaluation of Skin Biophysical Parameters and Angiogenesis Using CD34 as a Biomarker in Older Diabetic Women Treated with Radiofrequency.

Background: The prevalence of type 2 diabetes mellitus (t2DM) has been steadily increasing. Patients with t2DM need to slow down the skin ageing processes and to obtain a rejuvenating effect. Treatments that do not damage the superficial layers of the epidermis could be a promising solution for those patients. Purpose: The aim of this study was to evaluate the effects of radiofrequency therapy on the biophysical parameters and angiogenesis of facial skin, using CD34 as a biomarker in older diabetic women treated with metformin. Patients and Methods: A total of 45 subjects with phototype 2 or 3 (Fitzpatrick scale) were investigated (25 t2DM - study group, 20 - healthy controls). A series of 6 treatments (once a week) with a Radio Frequency Skin Rejuvenation System device was used on facial skin. Measurements of skin hydration, transepidermal water loss (TEWL), melanin and erythema index, temperature, and pH, at baseline and after radiofrequency therapy were performed with the Courage + Khazaka MPA-9 device. Immunohistochemistry on paraffin-embedded sections was used to evaluate the intensity of CD34 expression. Results: Radiofrequency treatment significantly improved facial skin hydration (p < 0.0001). Enhancement of the epidermal barrier observed, by reduced TEWL as a result of a series of treatments with radiofrequency on the facial skin (p < 0.0001), was observed. CD34 was more abundantly expressed after radiofrequency treatment. No side effects were observed. Conclusion: Treatment with radiofrequency is an effective and non-invasive method of facial skin rejuvenation in older women with t2DM, with a relatively short post-procedure recovery time and low potential for severe adverse effects.

Physicochemical Compatibility and Stability of Linezolid with Parenteral Nutrition.

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.