RESUMO

Diabetes mellitus (DM) is a highly prevalent disease affecting almost 10% of the world population; it is characterized by acute and chronic conditions. Diabetic patients have twenty-five times higher risk of going blind and developing cataracts early than the general population. Alpha-lipoic acid (LA) is a highly valuable natural antioxidant for the prevention and treatment of ophthalmic complications, such as diabetic keratopathy and retinopathy. However, its applicability is limited due to its low solubility in water; therefore, suitable systems are required for its formulation. In this work we developed an erodible insert based on Eudragit E100 (E PO) and Lipoic Acid (LA) for the delivery of this compound for the preventive treatment of ocular diseases especially in diabetic patients. Film evaluation was carried out by mechanical and thermal properties, mucoadhesivity, drug release, dynamic light scattering and corneal permeability as the concentration of LA increased. It was shown that upon LA release, it forms nanoparticles in combination with E PO that favor corneal permeation and LA retention in the cornea. These E PO-LA films also resulted non-irritable hence they are promising for their application in the treatment of ocular diseases.

RESUMO

Pharmacomagnetography involves the simultaneous assessment of solid dosage forms (SDFs) in the human gastrointestinal (GI) tract and the drug plasmatic concentration, using a biomagnetic technique and pharmacokinetics analysis. This multi-instrumental approach helps the evaluation, as GI variables can interfere with the drug delivery processes. This study aimed to employ pharmacomagnetography to evaluate the influence of omeprazole on the drug release and absorption of metronidazole administered orally in magnetic-coated tablets. Magnetic-coated tablets, coated with Eudragit® E-100 (E100) and containing 100 mg of metronidazole, were produced. For the in vivo experiments, 12 volunteers participated in the two phases of the study (placebo and omeprazole) on different days to assess the bioavailability of metronidazole. The results indicated a shift as the pH of the solution increased and a delay in the dissolution of metronidazole, showing that the pH increase interferes with the release processes of tablets coated with E100. Our study reinforced the advantages of pharmacomagnetography as a tool to perform a multi-instrumental correlation analysis of the disintegration process and the bioavailability of drugs.

RESUMO

Antimicrobial treatment alternatives for methicillin-resistant Staphylococcus aureus (MRSA) are increasingly limited. MRSA strains are resistant to methicillin due to the formation of ß-lactamase enzymes, as well as the acquisition of the mecA gene, which encodes the penicillin-binding protein (PBP2a) that reduces the affinity for ß-lactam drugs. Previous studies have shown that the use of ampicillin-loaded nanoparticles can improve antimicrobial activity on resistant S. aureus strains. However, the biological mechanism of this effect has not yet been properly elucidated. Therefore, this short communication focused on characterizing the in silico interactions of the PBP2a membrane receptor protein from S. aureus against the monomeric units of two polymeric materials previously used in the development of different nanoparticles loaded with ampicillin. Such polymers correspond to Eudragit E-100 chloride (EuCl) and the sodium salt of poly(maleic acid-alt-octadecene) (PAM-18Na). For this, molecular coupling studies were carried out in the active site of the PBP2a protein with the monomeric units of both polymers in neutral and ionized form, as well as with ampicillin antibiotic (model ß-lactam drug). The results showed that ampicillin, as well as the monomeric units of EuCl and PAM18Na, described a slight binding free energy to the PBPa2 protein. In addition, it was found that the amino acids of the active site of the PBPa2 protein have interactions of different types and intensities, suggesting, in turn, different forms of protein-substrate coupling.

RESUMO

RESUMEN La obtención de complejos polielectrolito entre el polímero catiónico Eudragit® E100 y moléculas aniónicas, con neutralización adicional de un ácido inorgánico, ha sido una práctica recurrente en el área de investigación de estos sistemas de liberación controlada. En el presente trabajo se buscó estudiar el efecto de la adición del ácido fuerte en el polímero, para ello se llevó a cabo la obtención por evaporación de solvente de diez complejos (de diferente composición entre Eudragit® E100 y ácido benzoico o ácido clorhídrico) y de cuatro ionómeros (sin el activo), a los cuales se les realizó análisis por FTIR y DSC. Los resultados demostraron la obtención de los respectivos complejos polielectro-lito y de los ionómeros; además los espectros de FTIR revelaron la relación directa entre la reacción de hidrólisis de los grupos ésteres del polímero y la proporción de HCl adicionada. Los termogramas, por su parte, evidenciaron la existencia de una reacción en el polielectrolito (PE), la cual se favoreció en aquellas composiciones en las que el proceso de hidrólisis ocurrió en mayor magnitud. El proceso de hidrólisis que se describe en el presente estudio debe tenerse en consideración en las futuras investigaciones en el campo, ya que su ocurrencia podría tener implicaciones en las diversas variables que se evalúan en este tipo de sistemas.

SUMMARY Polyelectrolyte complexes obtention between Eudragit® E100 (cationic polymer) and anionic molecules with additional neutralization of inorganic acids is a common practice in the development of these systems. In the present work the addition of strong acid effect on polymer structure was evaluated through FTIR and DSC analysis of a set of ten complexes with different composition (between Eudragit® E100 and benzoic acid) and four ionomers (without the preservative) obtained by solvent evaporation technique. Results demonstrated the complexes and ionomers formation. FTIR spectra revealed direct relationship between polymer ester groups hydrolysis reaction and the amount of HCl added. The thermograms, on the other hand, evidenced the existence of a reaction in the polyelectrolyte, which was favored in those compositions with more hydrolysis process. The degradation reaction described in this study should be taken into consideration in future research, since its occurrence could have implications in variables evaluated in this type of systems.

RESUMO

The commercial copolymers Eudragit® E 100 and Eudragit® PO are widely used materials in the pharmaceutical field as coating systems. Such materials derived from amino-methacrylate groups under acidulated conditions may acquire an ionisable fraction or undergo hydrolytic degradation of the polymeric structure. This work focused on establishing the chemical, physical, and surface changes of two reprocessed polymeric materials, here named as EuCl-E-100 and EuCl-E-PO, which were obtained from the commercial Eudragit® E 100 and Eudragit® E PO, respectively. The commercial materials were exposed to extreme acid conditions, where the polymers were solubilised and subsequently dried by the refractance window method. The materials obtained were chemically characterised by potentiometric titration, nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR) in one and two dimensions (COSY, HSQC, and HMBC), infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Changes in the physical properties of the materials were evaluated through studies of flowability, compactability, and their ability to gain and lose humidity. Surface thermodynamic studies were carried out through contact angle measurements using the sessile drop method. The results showed that the processed polymeric materials acquired a substantial degree of ionisation without undergoing hydrolysis of the esterified groups. Furthermore, such changes improved the flow characteristics of the material and the solubility in aqueous media at pH > 5, while also maintaining the hydrophobicity degree of the polymeric surface.

RESUMO

Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH)(50) (HCl)(50)) having fifty mole percent of each counterion (A(-) and Cl(-)) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH(3))CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH(2)-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from -(CH(3))CH-COOH complexes were clearly higher than those of -CH(2)-COOH ones.