Desenvolvimento de suspensão de micofenolato de sódio e sua viabilidade para administração por sonda de nutrição enteral

Abstract

Mycophenolic acid (AM) is the active ingredient (PA) found in Mycophenolate Sodium (MS) and Mycophenolate mofetil (MMF) tablets (CP). It is an immunosuppressant used in therapy against transplant rejection and autoimmune diseases. In Brazil, the only MS formulation available consists of coated CP with delayed release and gastro-resistant coating. MS therapy causes adverse reactions, mainly gastrointestinal, tending to decrease adherence to therapy, as well as the limitation expressed in users of enteral nutrition tubes. The present study sought to employ the pharmaceutical transformation starting from CP of MS in order to tolerate a suspension, using the aqueous vehicle GUTE, destined to be evaluated regarding the viability for administration via nasogastric tube. For this purpose, tests were used for the analytical validation of the obtained product, such as High Performance Liquid Chromatography (HPLC) and Ultraviolet-Visible Spectrophotometer (UV/VIS), which were able to characterize the product in terms of PA. Initially, orientation and identification of the oriented AP of the MS CP were carried out, after which a linearity test was carried out, which provided an R2 of 0.9999 and 0.9986, in UV/VIS and HPLC, respectively. Followed by the forced degradation test, in acidic, alkaline, oxidizing and aqueous medium, which did not indicate conclusive results in UV/VIS, in HPLC it was possible to verify the formation of deficiency products and significant loss, of 80% and 60% of PA in alkaline and oxidizing medium, respectively. From the suspension formulated with GUTE, antioxidants and pH adjustment were added in order to preserve the PA. Once the measurement was performed, HPLC demonstrated more precise and accurate indicators in relation to UV/VIS values. The quality control of the product was carried out through a stability test that lasted 88 days, evaluating: pH; rheological behavior; density; active content. Ensuring product quality for use despite certain conditions. It was found that, when inserted into the probe, it did not occur in the canal, however 13.3% of the content was lost, suggesting the need to use an occasional dose adjustment. Thus, the present work demonstrated the viability of the transformation and quality during the evaluated time, allowing the use of suspension as an alternative to the traditional presentation.