Polymorphism, crystallinity and hydrophilic-lipophilic balance of stearic acid and stearic acid-capric/caprylic triglyceride matrices for production of stable nanoparticles

There is an increasing interest in lipid nanoparticles because of their suitability for several administration routes. Thus, it becomes even more relevant the physicochemical characterization of lipid materials with respect to their polymorphism, lipid miscibility and stability, as well as the assessment of the effect of surfactant on the type and structure of these nanoparticles. This work focuses on the physicochemical characterization of lipid matrices composed of pure stearic acid or of mixtures of stearic acid-capric/caprylic triglycerides, for drug delivery. The lipids were analyzed by Differential Scanning Calorimetry (DSC), Wide Angle X-ray Diffraction (WAXD), Polarized Light Microscopy (PLM) and hydrophilic-lipophilic balance (HLB) in combination with selected surfactants to determine the best solid-to-liquid ratio. Based on the results obtained by DSC and WAXD, the selected qualitative and quantitative composition contributed for the production of stable nanoparticles, since the melting and the tempering processes provided important information on the thermodynamic stability of solid lipid matrices. The best HLB value obtained for stearic acid-capric/caprylic triglycerides was 13.8, achieved after combining these lipids with accepted surfactants (trioleate sorbitan and polysorbate 80 in the ratio of 10:90). The proposed combinations were shown useful to obtain a stable emulsion to be used as intermediate form for the production of lipid nanoparticles. (C) 2011 Elsevier B.V. All rights reserved.

Conformational Polymorphism in Racemic Crystals of the Diuretic Drug Chlortalidone

Chlortalidone (HIGROTON) is a diuretic drug widely used in antihypertensive therapy. Thus far, only two solid-state polymorphs of chlortalidone have been reported. We elucidated the structure of chlortalidone form I and a new polymorph. This new phase, namely, chlortalidone form III, was also entirely characterized. It was possible to conclude that it is a conformer with a different orientation of the chlorobenzenesulfonamide moiety. Compared to form I, it has a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted phenyl and isoindolinyl rings. This conformational feature is related to the crystal packing patterns of the chlortalidone forms. Furthermore, certain intermolecular hydrogen bonds are present in both polymorphs, giving rise to ribbons with chlortalidone enantiomers alternately placed into them. The chlortalidone form I and form III crystallize in the triclinic space group P (1) over bar as racemic mixtures. Additional conformational details also differentiate the chlortalidone conformers. Slight twists on the isoindolinyl and sulfamyl groups exist. Considering all structural relationships, the fingerprint plots derived from the Hirshfeld surfaces exhibited the characteristics of the chlortalidone form I and form III crystal structures.

Electrochemical Behavior of Verapamil at Graphite-Polyurethane Composite Electrodes: Determination of Release Profiles in Pharmaceutical Samples

A solid graphite-polyurethane composite electrode has been used to determine release profiles of verapamil, a calcium-channel blocker. The electro-oxidation process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy and showed no adsorption of analyte or oxidation products, unlike at other carbon-based electrodes. Quantification gave linear ranges up to 40molL-1 with cyclic voltammetry and detection limits of 0.7molL-1 by differential pulse and square-wave voltammetry. Commercial product samples were successfully analyzed with results equal to those from spectrophotometry. Because no electrode surface renewal is needed, this electrode material has many advantages.

Caracterização térmica (TG/DTG, DTA, DSC, DSC-fotovisual) de Hormônios bioidênticos (estriol estradiol)

Bioidentical hormones are defined as compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body. It is believed that the use of hormones may be safer and more effective than the non-bioidentical hormones, because binding to receptors in the organism would be similar to the endogenous hormone. Bioidentical estrogens have been used in menopausal women, as an alternative to traditional hormone replacement therapy. Thermal data of these hormones are scarce in literature. Thermal analysis comprises a group of techniques that allows evaluating the physical-chemistry properties of a drug, while the drug is subjected to a controlled temperature programming. The thermal techniques are used in pharmaceutical studies for characterization of drugs, purity determination, polymorphism identification, compatibility and evaluation of stability. This study aims to characterize the bioidentical hormones estradiol and estriol through thermal techniques TG/DTG, DTA, DSC, DSC-photovisual. By the TG curves analysis was possible to calculated kinetic parameters for the samples. The kinetic data showed that there is good correlation in the different models used. For both estradiol and estriol, was found zero order reaction, which enabled the construction of the vapor pressure curves. Data from DTA and DSC curves of melting point and purity are the same of literature, showed relation with DSC-photovisual results. The analysis DTA curves showed the fusion event had the best linearity for both hormones. In the evaluation of possible degradation products, the analysis of the infrared shows no degradation products in the solid state

Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Pharmaceutical applications of AC Biosusceptometry

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

Biomagnetic Methods: Technologies Applied to Pharmaceutical Research

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of solid and submerged fermentations for the production of cyclodextrin glycosyltransferase by Paenibacillus campinasensis H69-3 and characterization of crude enzyme

Cyclodextrin glycosyltransferase (CGTase) is an enzyme that produces cyclodextrins from starch by an intramolecular transglycosylation reaction. Cyclodextrins have been shown to have a number of applications in the food, cosmetic, pharmaceutical, and chemical industries. In the current study, the production of CGTase by Paenibacillus campinasensis strain H69-3 was examined in submerged and solid-state fermentations. P. campinasensis strain H69-3 was isolated from the soil, which grows at 45 C, and is a Gram-variable bacterium. Different substrate sources such as wheat bran, soybean bran, soybean extract, cassava solid residue, cassava starch, corn starch, and other combinations were used in the enzyme production. CGTase activity was highest in submerged fermentations with the greatest production observed at 48-72 h. The physical and chemical properties of CGTase were determined from the crude enzyme produced from submerged fermentations. The optimum temperature was found to be 70-75 degrees C, and the activity was stable at 55 degrees C for 1 h. The enzyme displayed two optimum pH values, 5.5 and 9.0 and was found to be stable between a pH of 4.5 and 11.0.

Detection of propranolol in pharmaceutical formulations by diffuse reflectance spectroscopy

This paper describes an analytical reflectometric method that has an objective not only the industrial quality control but also to detect possible falsifications and/or adulterations of propranolol in pharmaceutical formulations. The method is based on the diffuse reflectance measurements of the colored product (III) of the spot test reaction between propranolol hydrochloride (I) and 2,6-dichloroquinone-4-chloroimide (II) using filter paper as solid support. Spot test conditions have been investigated using experimental design in order to identify and optimize the critical factors. The factors evaluated were DCQ concentration, propranolol solvent and DCQ solvent. The best reaction conditions were achieved with the addition of 30 mu L, of propranolol solution in ethanol 35% (v/v) and 30 mu L of DCQ solution at 70 mg mL(-1) in acetone, in this order. All reflectance measurements were carried out at 500 nm and the linear range was from 8.45 x 10(-4) to 8.45 x 10(-2) mol L-1 (r= 0.998). The limit of detection was 1.01 x 10(-4) mol L-1. No interference was observed from the assessed excipients and drugs. The method was applied to determine propranolol in commercial brands of pharmaceuticals. The results obtained by the proposed method were favorably compared with those given by the British Pharmacopoeia procedure. (C) 2007 Elsevier B.V. All rights reserved.

Rapid spot test analysis for the detection of urotropine in pharmaceutical preparations

The widespread falsification and/or adulteration of commercially available pharmaceutical preparations call for reliable methods of drug identification, preferably through selective and rapid sorting color tests that could be undertaken with minimum equipment remote from laboratory facilities. The present work deals with a convenient adaptation and refinement of a spot test devised by Feigl (1966) for urotropine, based on the hydrolytic cleavage of that substance in the presence of sulfuric acid, splitting out formaldehyde which is identified by its color reaction with chromotropic acid. A simple emergency kit was developed for the quick, efficient, inexpensive and easy performance of urotropine tests by semiskilled personnel even in the drugstore laboratory (or office) as well as in a mobile screening operation. It is shown that when the reagents are added according to the recommended sequence a self-heating system is generated, increasing substantially the reactions' rates and the test sensitivity as well. The identification limit found was 25 mug of urotropine, for both solid and liquid samples. The possible interference of 84 substances/materials was investigated. Interference was noted only for methylene blue, acriflavine, Ponceau Red, Bordeaux Red (these dyes are often included in urotropine dosage forms), pyramidone, dipyrone, quinine and tetracycline. A simple procedure for removing most of the interferences is described. Data for 8 commercial dosage forms and results obtained from their analysis are presented.

Comparative investigation of the cleavage step in the synthesis of model peptide resins: Implications for N-alpha-9-fluorenylmethyloxycarbonyl-solid phase peptide synthesis

Based on our studies of the stability of model peptide-resin linkage in acid media, we previously proposed a rule for resin selection and a final cleavage protocol applicable to the N-alpha-tert-butyloxycarbonyl (Boc)-peptide synthesis strategy. We found that incorrect choices resulted in decreases in the final synthesis yield, which is highly dependent on the peptide sequence, of as high as 30%. The present paper continues along this line of research but examines the N-alpha-9-fluorenylmethyloxycarbonyl (Fmoc)-synthesis strategy. The vasoactive peptide angiotensin II (All, DRVYIHPF) and its [Gly(8)]-All analogue were selected as model peptide resins. Variations in parameters such as the type of spacer group (linker) between the peptide backbone and the resin, as well as in the final acid cleavage protocol, were evaluated. The same methodology employed for the Boc strategy was used in order to establish rules for selection of the most appropriate linker-resin conjugate or of the peptide cleavage method, depending on the sequence to be assembled. The results obtained after treatment with four cleavage solutions and with four types of linker groups indicate that, irrespective of the circumstance, it is not possible to achieve complete removal of the peptide chains from the resin. Moreover, the Phe-attaching peptide at the C-terminal yielded far less cleavage (50-60%.) than that observed with the Gly-bearing sequences at the same position (70-90%). Lastly, the fastest cleavage occurred with reagent K acid treatment and when the peptide was attached to the Wang resin.

Quantitative Phase Analyses Through The Rietveld Method with X-Ray Powder Diffraction Data of Heat-Treated Carbamazepine Form III

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

Magnetic images of pharmaceutical dosage forms in the human gastrointestinal tract

Oral administration with solid dosage forms is a common route in the drug therapy widely used. The drug release by the disintegration process occurs in several gastrointestinal tract (GIT) regions. AC Biosusceptometry (ACB) was originally proposal to characterize the disintegration process of tablets in vitro and in the human stomach, through changes in magnetic signals. The aim of this work was to employ a multisensor ACB system to monitoring magnetic tablets and capsules in the human GIT and to obtain the magnetic images of the disintegration process. The ACB showed accuracy to quantify the gastric residence time, the intestinal transit time and the magnetic images allowed to visualize the disintegration of magnetic formulations in the GIT. The ACB is a non-invasive, radiation free technique, completely safe and harmless to the volunteers and had demonstrated potential to evaluate pharmaceutical dosage forms in the human gastrointestinal tract. © 2005 IEEE.

A simplified reflectometric method for the rapid determination of dipyrone in pharmaceutical formulations

This paper describes a simple, portable and environmentally friendly method for the rapid determination of dipyrone in pharmaceuticals by using diffuse reflectance spectroscopy. The proposed method is based on the reflectance measurements of the orange compound produced from the spot test reaction between dipyrone and p-dimethylaminocinnamaldehyde (p-DAC), in acid medium, using a filter paper as solid support. Experimental design methodologies were used to optimize the measurement conditions. All reflectance measurements were carried out at 510 nm and the linear range was from 1.42 × 10-4-2.85 × 10-3 mol L-1, with a correlation coefficient of 0.999. The limit of detection (LOD) and the limit of quantification (LOQ) were 1.20 × 10-5 mol L-1 and 4.00 × 10-5 mol L-1, respectively. The intraday precision and interday precision were studied for 10 replicate analyses of 7.90 × 10-4 mol L-1 dipyrone solution. The coefficients of variation were 1.1 and 0.9%, respectively. The proposed method was applied successfully to the determination of dipyrone in commercial brands of pharmaceuticals. No interferences were observed from the common excipients in formulations. The results obtained by the proposed method were favorably compared with those given by the Brazilian Pharmacopoeia procedure at 95% confidence level. ©2007 Sociedade Brasileira de Química.