Publications by authors named "Simone Gonçalves Cardoso"

14 Publications

  • Page 1 of 1

The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation.

Eur J Pharm Sci 2020 Sep 10;152:105422. Epub 2020 Jun 10.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, United States. Electronic address:

Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=C/S), cocrystal solubility advantage over drug (SA=S/S), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and K values of 1:1 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolution, cocrystals regulate the interfacial pH (pH) to 1.6 for MLX-MLE and 4.5 for MLX-SLC, therefore diminishing the cocrystal dissolution rate dependence on bulk pH. Do values ranged from 2 (pH 6.5) to 410 (pH 1.6) and were mostly determined by the drug solubility dependence on pH. Drug release profiles show that maximum supersaturation (σ=C/Sand AUC increased with increasing Do as pH decreased. When Do>SA, the cocrystal solubility is not sufficient to dissolve the dose so that a dissolution-precipitation quasi-equilibrium state is able to sustain supersaturation for the extent of the experiment (24 h). When Do
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2020.105422DOI Listing
September 2020

Carbamide peroxide nanoparticles for dental whitening application: Characterization, stability and in vivo/in situ evaluation.

Colloids Surf B Biointerfaces 2019 Jul 4;179:326-333. Epub 2019 Apr 4.

Post Graduation Program in Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Brazil.

Carbamide peroxide is the popular home dental whitening agent. However, it has critical stability. Nanoparticles have been applied to develop products with advantages properties as better efficacy and stability increase. The aim of this study was the characterization of carbamide peroxide polymeric nanoparticles, their bleaching efficacy, effects on pulp damage and stability evaluation. Particle size demonstrated a spherical morphology and bimodal distribution (11 and 398 nm). Nanoparticles presented high entrapment efficiency (98.94%) and the zeta potential value was slightly positive (+10.26 mV). Regardless of the zeta potential, the steric effect may contribute to carbamide peroxide nanoparticle stabilization. The stability studies conducted at room temperature suggested that carbamide peroxide nanoparticles could maintain all the parameters evaluated (size, polydispersity index, zeta potential, entrapment efficiency, pH and content) for at least 90 days. Instability index was determined by dispersion analyzer (LUMiSizer ), was 0.018, and the light transmission profile did not present sedimentation. Carbamide peroxide nanoparticles were able to prevent thermal degradation and photostability. Clinical efficacy of the whitening gels was obtained by color change in the spectrophotometer and the results showed that all the evaluated gels containing the nanoparticles (0, 1, 2 and 5% of real carbamide peroxide) were effective at bleaching after 2 h of home whitening treatment (during 30 days). After the treatment, the extracted teeth showed no in situ pulp damage by histological evaluation. The nanotechnology strategy of converting carbamide peroxide into polymeric nanoparticles revealed a new product with improved stability, a good approach for carbamide peroxide delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2019.04.006DOI Listing
July 2019

Cocrystallization as a novel approach to enhance the transdermal administration of meloxicam.

Eur J Pharm Sci 2018 Oct 20;123:184-190. Epub 2018 Jul 20.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-970, Brazil. Electronic address:

Despite its large effectiveness, the long-term oral administration of high doses of meloxicam (MLX) may lead to gastrointestinal events such as abdominal pain, diarrhea, dyspepsia, ulceration, hemorrhage, and gastrointestinal perforation. Moreover, the pH-dependent solubility of MLX makes the development of new oral formulations even more challenging. As an alternative to overcome these limitations, the transdermal delivery of this drug has been purposed. Although various physical and chemical approaches to enhance the absorption of MLX may be found in literature, the use of cocrystallization has not been reported so far. Cutaneous permeation of MLX and 1:1 meloxicam-salicylic acid cocrystal (MLX-SLC) were evaluated using Franz diffusion cells. Cocrystal was suspended in an aqueous solution and in a gel to evaluate the vehicle effect on permeation parameters. In aqueous medium, the cocrystallization showed to enhance the drug permeation coefficient from 1.38 to 2.15 × 10 cm/h. MLX-SLC generated supersaturation with respect to the drug during dissolution studies simulating the conditions in the Franz cell donor chamber. This greater amount of free drug in the solution could contribute to explain the higher transdermal absorption and shorter lag time of this system. In addition, the acidic coformer ionization led to a pH reduction from 7.4 to 5.8, which, in turn, provided an increase in the unionized species of the drug, enhancing its permeation rate. The gel containing cocrystals reduced MLX permeation rate significantly (P = 0.42 × 10 cm/h), which was attributed to its higher viscosity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2018.07.038DOI Listing
October 2018

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant-like activity.

Biomed Chromatogr 2017 Nov 31;31(11). Epub 2017 May 31.

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by the forced swimming test, splash test and open field test. EFF-Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya. Quantitatively, EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosyl flavonoids. In addition, EFF-Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF-Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF-Cp exerts antidepressant-like effects with its antioxidant properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.3982DOI Listing
November 2017

Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5.

Adv Drug Deliv Rev 2016 06 29;101:143-166. Epub 2016 Apr 29.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor 48109-1065, MI, USA.

Besides enhancing aqueous solubilities, cocrystals have the ability to fine-tune solubility advantage over drug, supersaturation index, and bioavailability. This review presents important facts about cocrystals that set them apart from other solid-state forms of drugs, and a quantitative set of rules for the selection of additives and solution/formulation conditions that predict cocrystal solubility, supersaturation index, and transition points. Cocrystal eutectic constants are shown to be the most important cocrystal property that can be measured once a cocrystal is discovered, and simple relationships are presented that allow for prediction of cocrystal behavior as a function of pH and drug solubilizing agents. Cocrystal eutectic constant is a stability or supersatuation index that: (a) reflects how close or far from equilibrium a cocrystal is, (b) establishes transition points, and (c) provides a quantitative scale of cocrystal true solubility changes over drug. The benefit of this strategy is that a single measurement, that requires little material and time, provides a principled basis to tailor cocrystal supersaturation index by the rational selection of cocrystal formulation, dissolution, and processing conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2016.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910885PMC
June 2016

Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method.

Drug Dev Ind Pharm 2015 May 24;41(5):851-8. Epub 2014 Apr 24.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina , Florianópolis , Brasil .

Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/03639045.2014.909839DOI Listing
May 2015

Dissolution properties, solid-state transformation and polymorphic crystallization: progesterone case study.

Pharm Dev Technol 2014 Nov 13;19(7):779-88. Epub 2013 Sep 13.

Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina , Florianópolis , Brasil .

Progesterone is a natural steroid hormone and a poor soluble drug which presents two polymorphs (forms 1 and 2). Different methods to obtain form 2 were tested and a complete solid-state characterization of both polymorphs (forms 1 and 2) was conducted. X-ray powder diffraction, hot stage microscopy, Fourier transform infrared, dispersive Raman, (13)C solid-state nuclear magnetic resonance spectroscopy, thermal analysis, scanning electron microscopy techniques and intrinsic dissolution rates (IDR) were applied to investigate physical-chemical and dissolution properties of these two polymorphs. Form 2 was obtained from diluted solutions and from melting after cooling at room temperature. Form 1 was obtained from concentrated solutions and, a mixture of both polymorphs was crystallized from intermediate solutions. The crystal habit was not a distinctive characteristic of each polymorph. The effect of mechanical stress was evaluated in the metastable polymorph (form 2). We observed that grinding form 2 produced seeds of form 1 that induced the transformation of form 2 into form 1 at high temperature. The polymorphic quantification from XRD patterns of ground samples were carried out by the Rietveld method. After grinding and at room temperature conditions (∼25 °C), it was observed the transformation of 17% of form 2 into form 1 in 10 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10837450.2013.829096DOI Listing
November 2014

Development and physicochemical characterization of saquinavir mesylate solid dispersions using Gelucire 44/14 or PEG 4000 as carrier.

Arch Pharm Res 2013 Sep 23;36(9):1113-25. Epub 2013 May 23.

Laboratório de Virologia Aplicada, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.

Solid dispersions of saquinavir mesylate containing either Gelucire® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at -20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95% relative humidity and 40 °C/75% (f₂ values >50), respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-013-0142-2DOI Listing
September 2013

Single crystal structure, solid state characterization and dissolution rate of terbinafine hydrochloride.

J Pharm Biomed Anal 2013 May 13;78-79:105-11. Epub 2013 Feb 13.

Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-970, Brazil.

Terbinafine hydrochloride (TH), a poorly water soluble antifungal agent, was characterized by solid state techniques including differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, optical and electron microscopies, Fourier transform infrared, Raman and solid-state nuclear magnetic resonance spectroscopies and intrinsic dissolution rate (IDR). A colorless single crystal of TH was grown from an ethanol:water solution and its crystalline structure was determined through X-ray single crystal diffraction. Also, a new crystal habit of TH was obtained through the slow solvent evaporation technique revealing a needle-like shape. A comparison between the IDR results for the TH raw material and TH needle-like crystal revealed lower values for the new crystal habit, which can be attributed to the preferential orientation of the crystals in the compressed disks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2013.02.001DOI Listing
May 2013

HIV/AIDS treatment and physicochemical quality control of medicines: evaluation of non-generic lamivudine + zidovudine tablets manufactured in Brazil.

Braz J Infect Dis 2007 Dec;11(6):540-3

Department of Pharmaceutical Industry, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.

In this work it was evaluated the physicochemical quality of lamivudine + zidovudine tablets, whose association belongs to the list of drugs distributed by the Brazil's National Program on Sexually Transmitted Diseases and AIDS. Four non-generic products (lamivudine + zidovudine tablets) were analyzed. They were obtained from different Brazilian manufacturers, besides a reference product. The quality was evaluated by physicochemical tests described in the official codes. A validated reversed-phase high performance liquid chromatography (HPLC) method was used for the assay of the active substances. All samples were in accordance to the requisites in relation to their physicochemical characteristics. Dissolution studies showed similar drug percentual dissolved among all samples. The results reflect the interest of the national pharmaceutical industry to ensure the delivery of safer and cheaper drugs to the Brazilian people, with particular importance in the National Program on Sexually Transmitted Diseases and AIDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/s1413-86702007000600003DOI Listing
December 2007

Determination of amlodipine in pharmaceutical dosage forms by liquid chromatography and ultraviolet spectrophotometry.

J AOAC Int 2006 Mar-Apr;89(2):359-64

Universidade Federal de Santa Maria, Departamento de Farmácia Industrial, Santa Maria, CEP 97.119-900, RS, Brazil.

A liquid chromatography (LC) method and an ultraviolet (UV) spectrophotometric method were developed and validated for quantitative determination of amlodipine in tablets and compounded capsules. The isocratic LC analyses were performed on an RP18 column using a mobile phase composed of 0.1% (v/v) ortho-phosphoric acid (pH 3.0) -acetonitrile (60 + 40, v/v) at a flow rate of 1.0 mL/min. The UV spectrophotometric method was performed at 238 nm. The analytical methods were validated according to International Conference on Harmonization Guidelines. The calibration graphs were linear [correlation coefficient (r) > 0.999] in the studied concentration range of 10-30 microg/mL for LC and 10-35 microg/mL for UV spectrophotometry. The relative standard deviation values for intraday and interday precision studies were less than 2%, and the accuracy was greater than 98% for both methods. The specificity of the LC method was proved using forced degradation. Statistical analyses showed no significant difference between the results obtained by the 2 methods. The proposed methods are precise and accurate and can be applied directly and easily to the oral pharmaceutical preparations of amlodipine.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2006

Validation of UV spectrophotometric and nonaqueous titration methods for the determination of carvedilol in pharmaceutical formulations.

J AOAC Int 2005 Sep-Oct;88(5):1299-303

Universidade Federal de Santa Maria, Departamento de Farmácia Industrial, Santa Maria, RS, Brazil, CEP 97105-900.

Ultraviolet (UV) spectrophotometric and nonaqueous volumetric methods are described for the determination of carvedilol in pharmaceutical formulations. Linearity, precision, and accuracy were evaluated according to the validation guidelines of the International Conference on Harmonization and the United States Pharmacopeia for both methods. The UV spectrophotometric procedure was performed in ethanol at 244 nm. Good linearity was obtained between 2 and 7 microg/mL with a correlation coefficient of 0.9999. The intra- and interday precision values were <2% for all samples analyzed. The accuracy, determined from recovery studies, was between 97.5 and 102.2%. The other procedure was based on the volumetric quantitation of carvedilol in a nonaqueous medium with 0.01 M perchloric acid and 1% violet crystal as the indicator. The validation of the volumetric method yielded good results that included linearity (r of > 0.999), precision (relative standard deviations of <2% for intra- and interday precision), and accuracy (96.4-102.4%). The methods were applied to tablets and compounded capsules. Statistical analysis by analysis of variance showed no significant difference between the results obtained by the proposed methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2006

Spectrophotometric determination of oxiconazole in topical lotion using methyl orange.

J Pharm Biomed Anal 2005 Apr 21;37(4):639-42. Epub 2004 Dec 21.

Universidade Federal de Santa Maria, Departamento de Farmácia Industrial, Santa Maria, CEP 97119-900-RS, Brazil.

A spectrophotometric method is described for the determination of oxiconazole in raw material and in topical lotion. This method is based on the reaction of the oxiconazole with methyl orange in buffered aqueous solution of citric acid at pH 2.3. The chromogen, being extractable with dichloromethane, could be measured quantitatively with maximum absorption at 427 nm. The Lambert-Beer law was obeyed in the concentration range of 4.0-14.0 microg ml(-1). A prospective validation of the method showed that the method was linear (r=0.9995), precise (intra-day: CV=1.57% and inter-day: CV=1.50%) and accurate (mean recoveries: 99.69%). The results compared favourably with those of the HPLC method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2003.09.003DOI Listing
April 2005

LC method for the analysis of Oxiconazole in pharmaceutical formulations.

J Pharm Biomed Anal 2002 Sep;30(2):175-80

Departamento de Farmácia Industrial, Programa de Pós-Graduação em Ciência e Tecnologia Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, CEP 97.119-900, RS, Brazil.

A LC method has been developed for the quantitative determination of Oxiconazole (Ox) in bulk form, lotion and cream pharmaceutical formulations. The method validation yielded good results including the range, linearity, precision, accuracy, recovery, specificity, robustness, limit of quantitation and limit of detection. The LC separation was carried by reversed phase chromatography using a LiChrocart C(8) column (125 mm x 4.0 mm i.d., 5 microm particle size). The mobile phase was composed of methanol-0.02 M ammonium acetate buffer (85:15 v/v), pumped isocratically at flow rate 1 ml min(-1). The detection was carried out on UV detector at 254 nm. The calibration curve for Ox was linear from 40.0-140.0 microg ml(-1) range. The precision of this method, calculated as the relative standard deviation (R.S.D.) was 1.57% for lotion and 0.71% for cream. The R.S.D. values for intra- and inter-day precision studies were 0.57 and 1.34%, respectively. The recovery of the drug ranged between 98.84-102.2% (lotion) and 100.54-101.59% (cream). The stability indicating capability of the assays was proved using forced degradation. Chromatograms showed Ox well resolved from the degradation product.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0731-7085(02)00171-1DOI Listing
September 2002