Monica Felts de La Roca Soares

Inclusion complex of methyl-β-cyclodextrin and olanzapine as potential drug delivery system for schizophrenia.

Olanzapine (OLP), the most important atypical antipsychotic drug of the new generation, a high cost drug, has low aqueous solubility, affecting its dissolution and absorption. Its complexation with modified cyclodextrins (CDs) is designed to achieve novel vectorization systems with higher solubility, consequently higher bioavailability. From the CD selection, among β-CD, methyl-β-CD (MβCD) and hydroxypropyl-β-CD, it was obtained a phase solubility diagram suggesting a 1:1 (mol:mol) OLP-CD stoichiometry and complexation constants of 966.9, 149.4 and 91.1 L/mol, respectively. The MβCD was selected for the inclusion complexes (IC) attainment, a physical mixture (PM) and a rotatory evaporator product (ROE). The analysis showed differences in the structure, morphology and performance of OLP, MβCD, PM and ROE, revealing the occurrence of interactions between drug and CD. The ROE presented the higher dissolution efficiency and stability. The results suggest that the IC was formation, being a technological resource efficient and profitable for drug delivery.

Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods.

Efavirenz (EFV) used as a part of the treatment of first choice in antiretroviral therapy for AIDS has low aqueous solubility and presents problems of absorption. We thus initially present a phase solubility diagram with carriers of different classes. With a view to obtaining a solid dispersion (SD) with suitable consistency to that of a solid formulation, we chose to use PVP K-30, since polymers present some of the best results. The kneading (KN) and solvent evaporation (EV) methods were thus used at different rates. These were characterized by the way of DSC, FT-IR, SEM, DR-X and dissolution. SD EV proved unsatisfactory, resulting in a decreased dissolution rate, despite the amorphous state of the samples, while the SD KN 4:1 (EFV:polymer) and physical mixtures (PM) had a higher rate of dissolution. SD KN and PM 4:1 were also evaluated for stability after storage, with benefits being observed in relation to EFV.

Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers

Benznidazole (BNZ) is the drug of choice for Chagas disease treatment, which affects about 9.8 million people worldwide. It has low solubility and high toxicity. The present study aimed to develop and characterize inclusion complexes (IC) in binary systems (BS) with BNZ and randomly methylated-β-cyclodextrin (RMβCD) and in ternary systems (TS) with BNZ, RMβCD and hydrophilic polymers. The results showed that the solid BS had a large increase in dissolution rate (Q>80%). For the solid IC obtained, the kneading method, in ratio of 1:0.17 (77.8% in 60 min), appeared to be the most suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and low concentration of CD. The solid TS containing 0.1% of hydroxypropylmethylcellulose (HPMC) showed no significant advantages compared to the binary IC in solid state. The use of cyclodextrins proved to be a viable tool for effective, standardized and safe drug delivery.

Study of stability and drug-excipient compatibility of diethylcarbamazine citrate

Diethylcarbamazine citrate (DEC) is the main drug used in the lymphatic filariasis treatment. This study aimed to evaluate drug-excipient compatibility of binary mixtures (BMs) (1:1, w/w), initially by differential scanning calorimetry (DSC), and subsequently, if there were any interaction evidence, by complementary techniques, such as thermogravimetric (TG), non-isothermal kinetics, Fourier transform infrared (FT-IR), and X-ray diffraction (XRD). For the analyses of the BMs by DSC, we selected those with Tabletose®, representing the excipients containing lactose, polivinilpirrolidona (PVP), and magnesium stearate (MgS). The additional analyses by FT-IR and XRD showed no interaction evidence. The TG curves of DEC–Tabletose® showed no signs of interaction, unlike the TG curves of PVP and MgS, confirming the results of non-isothermal kinetics, in which the BMs with PVP and MgS decreased the reaction activation energy. Thus, it was concluded after evaluation that the excipients, especially the PVP and MgS, should be avoided.

Gums' based delivery systems: Review on cashew gum and its derivatives.

The development of delivery systems using natural polymers such as gums offers distinct advantages, such as, biocompatibility, biodegradability, and cost effectiveness. Cashew gum (CG) has rheological and mucoadhesive properties that can find many applications, among which the design of delivery systems for drugs and other actives such as larvicide compounds. In this review CG is characterized from its source through to the process of purification and chemical modification highlighting its physicochemical properties and discussing its potential either for micro and nanoparticulate delivery systems. Chemical modifications of CG increase its reactivity towards the design of delivery systems, which provide a sustained release effect for larvicide compounds. The purification and, the consequent characterization of CG either original or modified are of utmost importance and is still a continuing challenge when selecting the suitable CG derivative for the delivery of larvicide compounds.

Palygorskite organophilic for dermopharmaceutical application

Due to the growing interest of the population in natural treatments, the clays represent a good alternative to the treatment of wounds. Its modification by organophilization happens when the same inorganic cations are exchanged for organic cations of the surfactant used in the process. Thus, the clay has the properties of its surface modified from being hydrophilic to hydrophobic, improving its functionality on the skin. In order to determine changes in surface palygorskite and to assess its healing action, this clay was organophilizated by two cationic surfactants: dimethyl benzyl ammonium chloride alkyl, and cetyl trimethyl ammonium chloride, and characterized by sieve analysis, property flow, test oil adsorption, and the techniques of X-ray fluorescence, X-ray diffraction, infrared Fourier transform, thermogravimetric analysis, scanning calorimetry—differential and histological of cutaneous wounds in rats. The results indicate that the attapulgite has good rheological properties, a high capacity of adsorption of oil, and the presence of clay minerals that reduce inflammation. The analysis by X-ray fluorescence is not observing any change in the crystal structure of palygorskite organophilizated but through infrared spectroscopy Fourier transform, verifying the interaction and incorporation of the clay ammonium salts, as well as thermoanalytical analysis also suggests that the organophilic process reduces the hydrophilic character of palygorskite. The histological analysis showed healing effect after topical application of natural and organophilizated clay in skin wounds in rats. These analyses favor a good prospect of its application in dermopharmaceuticals, because the use of palygorskite provides greater interaction with skin and heals wounds.

The efficacy of photodynamic therapy and sodium hypochlorite in root canal disinfection by a single-file instrumentation technique

AIM The aim of this in vitro study was to evaluate the efficacy of photodynamic therapy (PDT) and sodium hypochlorite (NaOCl) in root canal disinfection by a single-file instrumentation technique. MATERIAL AND METHODS Seventy human single-rooted mandibular premolars were infected with Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, and divided into seven groups (n=10) according to the protocol of disinfection used. Group 1: 1% NaOCl; Group 2: 5.25% NaOCl; Group 3: saline+PDT; Group 4: 1% NaOCl+PDT; Group 5: 5.25% NaOCl+PDT; Group 6: positive control; Group 7: negative control. For PDT, methylene blue (15μg/mL) remained in the root canal for 2min, followed by irradiation with diode laser. Samples were collected before and after instrumentation and plated in specific media cultures, to assess the presence or absence of microbial growth and determine the average reduction of viable microorganisms. RESULTS 5.25% NaOCl+PDT resulted in the highest number of specimens with no microbial growth. Also, 1% NaOCl and 1% NaOCl+PDT exhibited similar antimicrobial effects. Saline+PDT was not able to eliminate all microorganisms. There was statistical significant differences between the groups and the microorganisms. CONCLUSION The association of 5.25% NaOCl with PDT was the most effective treatment against microorganisms from endodontic infection in root canals instrumented by a single-file instrumentation technique. This result shows that PDT can be useful to improve the root canal disinfection.

Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz

Efavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins).

Enhancement of dissolution rate through eutectic mixture and solid solution of posaconazole and benznidazole

Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal compound posaconazole (PCZ) have shown synergistic action in the therapy of Chagas disease, however both active pharmaceutical ingredients (APIs) exhibit low aqueous solubility potentially limiting their bioavailability and therapeutic efficacy. In this paper, we report for the first time the formation of a eutectic mixture as well as an amorphous solid solution of PCZ and BNZ (at the same characteristic ratio of 80:20wt%), which provided enhanced solubility and dissolution rate for both APIs. This eutectic system was characterized by DSC and the melting points obtained were used for the construction of a phase diagram. The preservation of the characteristic PXRD patterns and the IR spectra of the parent APIs, and the visualization of a characteristic eutectic lamellar crystalline microstructure using Confocal Raman Microscopy confirm this system as a true eutectic mixture. The PXRD result also confirms the amorphous nature of the prepared solid solution. Theoretical chemical analyses indicate the predominance of π-stacking interactions in the amorphous solid solution, whereas an electrostatic interaction between the APIs is responsible for maintaining the alternating lamellar crystalline microstructure in the eutectic mixture. Both the eutectic mixture and the amorphous solid solution happen to have a characteristic PCZ to BNZ ratio similar to that of their pharmacological doses for treating Chagas disease, thus providing a unique therapeutic combination dose with enhanced apparent solubility and dissolution rate.

Desenvolvimento de método analítico para quantificação do efavirenz por espectrofotometria no UV-Vis

An UV-Vis spectrophotometry analytical method for quantifying Efavirenz was developed and validated as an alternative to replace the HPLC current method. The report method presents sample concentration of 10 μg mL-1, dissolved in a solution ethanol:water (60:40, v/v), economic and technically adequate for the purpose adopted. The results and the statistical treated proved that the method being considered an precise and accurate analytical low cost alternative for laboratory routine. The adaptability of this method in product and other analytical methods development has been challenged by mathematical calculation of drug extinction coefficient in water and methanol and practical experiments, showing interesting results.