Development and characterization of a biocompatible soybean oil-based microemulsion for the delivery of poorly water-soluble drugs

The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin®HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3535-3543, 2015.

Effects of season and ovarian status on the outcome of long-term progesterone-based estrus synchronization protocols and ovulatory follicle development in Santa Inês ewes under subtropical conditions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and characterization of cefoxitin loaded D,L-PLA nanoparticles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and validation of a simple, rapid and stability-indicating high performance liquid chromatography method for quantification of norfloxacin in a pharmaceutical product

A stability-indication high performance liquid chromatographic method has been developed for the determination of norfloxacin in tablet dosage forms. Optimum separation was achieved in less than 7 minutes using Eclipse Plus Zorbax C18 Agilent, 150 mm×4.6 mm i.d., 5 μm particle size column. The analyte was resolved by using a mobile phase 5% acetic acid aqueous solution and methanol (80:20, v/v) at a flow rate 1.0 ml/min on an isocratic high performance liquid chromatographic system at a wavelength of 277 nm. Linearity, system suitability, precision, sensitivity, selectivity, specific, and robustness were established by International Conference Harmonization guidelines. For stress studies the drug was subjected to photolysis, oxidation, acid, alkaline and neutral conditions. The analytical conditions and the solvent developed provided good resolution within a short analysis time and economic advantages. The proposed method not required sophisticated and expensive instrumentation.

Development and validation of first derivative spectrophotometric method for quantification of darunavir in tablets

Aims: Darunavir is widely used in HIV/AIDS therapy. It is a HIV protease inhibitor that has excellent efficacy against the virus. The aim of this study is to develop and validate an analytical method fast and free of interferences for determination of darunavir ethanolate as raw material and tablet dosage form. Methodology: As the formulation excipients show high interference in darunavir determination by a direct UV absorption measurement a derivative spectrophotometry was applied. A selective, easy and fast method was achieved employing simple and cheap instrumentation by using first-order derivative spectrophotometry. Results: The first-derivation of spectrum of the drug measured between 200 and 400 nm allowed identification of the analyte and showed absence of placebo interference. The assay was based on the absorbance at 276nm. The linear concentration range was established from 11 to 21 μg/mL. The intra-day and inter-day precision expressed as RSD was 0.06% and 3.75% respectively with mean recovery of 99.84%. Conclusion: The proposed analytical method is able to quantify darunavir as raw material and tablets and can be used routinely by any laboratory applying a spectrophotometer with a derivative accessory. The great difference of the method proposed here is that it proves to be free of placebo interferences as well as simple, fast and low cost.

Dendrimers as potential platform in nanotechnology-based drug delivery systems

The dendrimers of poly (amidoamine) (PAMAM) are nanoparticles which have proven succeed in transporting drugs due to high solubility, low toxicity and ability to control drugs release. Studies have explored the biological potential of dendrimers such as to transport genes, development of vaccines, antiviral, antibacterial and anticancer therapies. This review of literature on the PAMAM dendrimers discusses the architecture and general construction of dendrimers and intrinsic properties of the PAMAM. This study also describes how the PAMAM interact with many drugs and the potential of these macromolecules as well as drug nanocarriers in transdermal routes of administration, ocular, respiratory, oral and intravenous administration. Dendrimers promises good future prospects for the biomedicine.

Development and validation of a stability-indicative turbidimetric assay to determine the potency of doxycycline hyclate in tablets

The doxycycline (DOX) is a broad-spectrum antibiotic used in several countries. This drug is part of the list of medicines to the SUS (Unified Health System), a model of health care in Brazil. This study describes the development and validation of a microbiological assay, applying the turbidimetric method for the determination of DOX, as well as the evaluation of the ability of the method in determining the stability of DOX in tablets against acidic and basic hydrolysis, photolytic and oxidative degradations, using Escherichia coli ATCC 10536 as micro-organism test and 3×3 parallel line assay design, with nine tubes for each assay, as recommended by the Brazilian Pharmacopoeia. The developed and validated method showed excellent results of linearity, selectivity, precision, accuracy and robustness. The assay is based on the inhibitory effect of DOX using Escherichia coli ATCC 10536. The results of the assay were treated by analysis of variance and were found to be linear (r= 0.9986) in the range from 4.0 to 9.0μg/mL, precise (repeatability R.S.D.= 0.99 and intermediate precision was confirmed by statistical analysis the mean values obtained from analysis by different analysts) and exact (97.73%). DOX solution exposed to direct UV light, alkaline and acid hydrolysis and hydrogen peroxide causing oxidation were used to evaluate the specificity of the bioassay. Comparison of bioassay and liquid chromatography showed differences in results between methodologies. The results showed that the bioassay is valid, simple and useful alternative methodology for DOX determination in routine quality control.

Development and in vitro skin delivery of dexamethasone acetate-loaded surfactant-based systems

Topical corticosteroids, e.g., dexamethasone acetate (DMA), are extensively used to treat cutaneous inflammatory disorders even though their use is correlated with potential local and systemic side effects. The objective of this study was to develop and test the topical delivery of DMA-loaded surfactant based systems in vitro; these studies could guarantee a suitable delivery and therapeutic efficacy, as well as minimize DMA's side effects. A phase diagram was constructed using polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as the surfactant (S), isopropyl myristate as the oil phase (O) and water (W). The systems were characterized using polarization light microscopy (PLM), as well as rheological and small angle X-ray scattering (SAXS) measurements. Depending on the concentration of the constituents, it was possible to obtain microemulsions (MEs) and liquid crystalline mesophases (lamellar and hexagonal). These types of arrangement were verified using PLM measurements. The SAXS results revealed that increasing the W/S ratio led to ME, as well as lamellar (LAM) and hexagonal (HEX) arrangements. The MEs displayed typical Newtonian behavior while the LAM and HEX phases exhibited pseudoplasticity and plasticity, respectively. The MEs displayed excellent drug solubilization that was approximately 10-fold higher than was observed with the individual components. The in vitro cutaneous permeation studies using pig ear skin and analysis of the mechanical parameters (hardness, compressibility, cohesiveness and adhesiveness) were carried out with a HEX phase and O/W emulsion. The HEX phase achieved better drug permeation and retention in the skin while its mechanical properties were suitable for skin administration. PPG-5-CETETH-20-based systems may be a promising platform delivering DMA and other topical corticosteroids through the skin.

Development and validation of an LC-MS/MS method for quantitative analysis of mirtazapine in human plasma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and analysis of formulations to the delivery of caffeine for the treatment of gynoid lipodystrophy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)