Paulo Mayorga

Influence of β-cyclodextrin complexation on carbamazepine release from hydroxypropyl methylcellulose matrix tablets

The in vitro release profiles of carbamazepine and beta-cyclodextrin either complexed or simply mixed and subsequently incorporated in hydrophilic matrix tablets containing 15 or 30% hydroxypropyl methylcellulose were evaluated. Solubility studies revealed a linear relationship between the increase in carbamazepine solubility and the increase in beta-cyclodextrin concentration. Drying methods (spray-drying and freeze-drying) were used to obtain carbamazepine/beta-cyclodextrin solid complexes in order to prepare tablets. The results demonstrated that matrix tablets containing carbamazepine/beta-cyclodextrin solid complexes displayed faster carbamazepine and beta-cyclodextrin release compared to that containing simple physical mixture. Gelling and matrix formation was impaired in formulation containing 15% hydroxypropyl methylcellulose and spray-dried complex. The comparison of spray-drying and freeze-drying revealed no significant influence of both drying methods on carbamazepine and beta-cyclodextrin dissolution rate when carbamazepine/beta-cyclodextrin complexes were incorporated in 30% hydroxypropyl methylcellulose matrix tablets. The results point to the possibility of modulating carbamazepine release using a hydroxypropyl methylcellulose matrix associated to the drug complexed with beta-cyclodextrin.

Counterfeit Cialis and Viagra fingerprinting by ATR-FTIR spectroscopy with chemometry: Can the same pharmaceutical powder mixture be used to falsify two medicines?

This paper proposes a direct and efficient method to discriminate between counterfeit and authentic Cialis and Viagra samples by combining attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy with multivariate techniques. The chemical profile of 53 commercial samples (Viagra(®), Cialis(®)) and 104 counterfeit samples (Viagra and Cialis) from distinct seizures were obtained from ATR-FTIR data derived from 10mg of crushed core tablets. Principal component analysis (PCA) technique was employed to classify samples based on the fingerprint region mid-infrared spectra (1800-525 cm(-1)) using OMNIC v.7.2 software; PCA enabled categorizing samples in groups with different chemical profiles, successfully distinguishing between authentic and counterfeits samples in forensic routine. The existence of active pharmaceutical ingredients (API) and technological adjuvant others than specified on the medicine package were also detected in counterfeit samples. In addition, we applied the similarity match (SM) method to demonstrate that a mixture of pharmaceutical powders deriving from a common origin may have been used to manufacture both counterfeit Cialis and Viagra tablets from distinct seizures.

Fingerprinting of sildenafil citrate and tadalafil tablets in pharmaceutical formulations via X-ray fluorescence (XRF) spectrometry.

The production of counterfeited drugs is a criminal problem that carries serious risks to public health in the worldwide. In Brazil, Viagra and Cialis are the most counterfeit medicines, being used to inhibit the phosphodiesterase type 5 (PDE-5), treating thus, problems related to erectile dysfunction. X-ray fluorescence (XRF) is a suitable technique to control the quality of new pharmaceutical formulations and distinguish between authentic and counterfeit tablets. XRF has advantageous features like multielemental capability, good detectivity, high precision, short analysis times, and is nondestructive, which makes it suitable to be extended to a great variety of samples. In this work, the inorganic fingerprinting chemical of forty-one commercial samples (Viagra, Cialis, Lazar, Libiden, Maxfil, Plenovit, Potent 75, Rigix, V-50, Vimax and Pramil) and fifty-six counterfeit samples (Viagra and Cialis) were obtained from XRF data. XRF presented an excellent analytical methodology for semi-quantitative determination of active ingredient (in case of sildenafil citrate that presents S in its structure) and excipients such as calcium phosphate, titanium oxide and iron oxide (P, Ca, Ti and Fe). The matrix data were allied to chemometric methods (Principal Component Analysis and Hierarchical Cluster Analysis) to classify the tablets investigated between authentic and counterfeit, grouping the samples into of seven groups: A, B, C, D and E (counterfeit group) and F and G (authentic group).

A new methodology for detection of counterfeit Viagra® and Cialis® tablets by image processing and statistical analysis

This paper proposes a new approach for automatic classification of counterfeit Viagra(®) and Cialis(®) tablets using image processing and statistical analysis. A high resolution VSC 5000 is used for image acquisition in a controlled environment, and the combination of a thresholding technique with morphological operators is used to segment the tablet from the background. A statistical model based on the RGB color components of original samples is built, and the detection of counterfeit tablets was performed by checking the adherence of a test sample to the obtained distribution using the Bhattacharyya distance. Our experimental results indicated that counterfeit tablets can be effective detected using the proposed approach.

Solid state evaluation of some thalidomide raw materials.

Thalidomide presents polymorphism and is a problematic drug due to its poor solubility and difficult tablet processability, which is the dosage form available in Brazil. In most cases, the pharmacopoeias specify do not address solid state characterization of drugs precisely. In this work, different thalidomide commercial samples were characterized by infrared spectroscopy, particle size analysis, scanning electron microscopy, and X-ray diffraction. In addition, the polymorphic forms were quantified for Rietveld analysis and their intrinsic dissolution rates were evaluated. The results demonstrated the market availability of different raw materials which lack of homogeneity due to differences related to crystalline constitution, crystal habit and intrinsic dissolution rate.

A multivariate-based wavenumber selection method for classifying medicines into authentic or counterfeit classes.

Attenuated total reflectance (ATR), a sampling technique by Fourier transform infrared (FTIR) spectroscopy, has been adopted as an analytical tool for detecting fraudulent medicines. The spectrum generated by FTIR-ATR typically relies on hundreds of equally spaced wavenumbers which may reduce the performance of techniques tailored to classify samples into classes, i.e., authentic or fraudulent. This paper proposes a novel method for selecting subsets of wavenumbers (variables) that better classify samples into such classes. For that matter, principal components analysis (PCA) is integrated to the k-nearest neighbor (KNN) classification technique. PCA is applied to FTIR-ATR data, and a variable importance index is built on the PCA outputs. An iterative backward variable elimination is started guided by that index; after each variable removal, samples are categorized into authentic or fraudulent classes using KNN, and the classification accuracy is measured. The wavenumber subset compromising high accuracy and reduced percent of retained variables is chosen. When applied to Cialis FTIR-ATR data, the proposed approach retained only average 1.84% of the original variables and increased the classification accuracy average 2.1%, to 0.9897 from 0.9689; as for Viagra data, the method increased average classification accuracy 1.56%, from 0.9135 to 0.9278, using only 7.72% of the original variables.

Profiling counterfeit Cialis, Viagra and analogs by UPLC–MS

In this work, the chemical profile of 43 commercial samples of tablets for male erectile dysfunction (Viagra, Cialis, Lazar, Libiden, Maxfil, Plenovit, Potent 75, Rigix, Vimax, Pramil 75 and Pramil) and 65 counterfeit samples (Viagra and Cialis) were obtained from UPLC-MS data. Methanol extracts of crushed tablets were investigated by ultra performance liquid chromatography (UPLC) with diode array detection (DAD) coupled with eletrospray ionization in the positive ion mode (ESI(+)) quadrupole time-of-flight (Q-Tof) mass spectrometry (MS). A validated method was employed for the simultaneous determination of sildenafil citrate (SLD) and tadalafil (TAD). The ultra-chromatograms obtained with method provide high resolution of MS, and are a quick (less to 1.5 min) and reliable tool in the distinction between authentic and counterfeit tablets. It was observed in most cases the presence of other active pharmaceutical ingredients (APIs) than specified on the package (TAD and SLD). Additionally, high concentrations of TAD and SLD were detected in counterfeit samples when compare with observed values for a typical commercial product. Chemometric methods were employed and the samples were grouped in five groups as function of API content.

Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails.

This work aimed to evaluate the effect of different substances on the permeation of geraniol through bovine hoof membranes. Different penetration enhancers were able to increase the permeability up to 25 times compared to control. It was demonstrated that acetilcysteine in association with ascorbic acid increased the permeation, even in acid formulations. In addition, some antifungal drugs were incorporated into a gel formulation of HPMC containing acetylcysteine 5% and ascorbic acid 0.2% and then the permeation coefficient through bovine hoof membranes was evaluated. The relationship between permeability and molecular weight was established for fluconazole, miconazole, terbinafine, butenafine, geraniol and nerol. Geraniol and nerol, the antifungals with lower molecular weight, had the better permeability results. Permeability coefficients for nail plates were estimated and geraniol demonstrated similar or even better efficacy index values against T. rubrum, T. menthagrophytes and M. canis compared with terbinafine and miconazole.

Improvement of genistein content in solid genistein/β- cyclodextrin complexes

Genistein:β-cyclodextrin complexes with high drug loading (19.22%) were prepared by freeze-drying and characterized by differential scanning calorimetry and hydrogen nuclear magnetic resonance spectroscopy. The spatial configuration of the complex was proposed by means of 2D-NOESY experiment combined with molecular modeling. According to the results obtained, the interaction of genistein with β -cyclodextrin in a 1:1 complex is supposed to occur mainly through the insertion of the guest A-ring in cyclodextrin cavity, without rule out the possibility of inclusion through the B-ring, as previously reported in the literature.

Carbamazepine/βCD/HPMC Solid Dispersions. I. Influence of the Spray-Drying Process and βCD/HPMC on the Drug Dissolution Profile

Abstract The aim of this study was to compare carbamazepine (CBZ) solid dispersions prepared by spray-drying of aqueous dispersions with the corresponding physical mixtures. The influence of the association of β-cyclodextrin (βCD) and hydroxypropyl methylcellulose (HPMC) on the CBZ dissolution profile of the preparations was investigated. Results demonstrated that CBZ release from solid dispersions is dependent on the ratio of βCD and HPMC. The spray-drying process confers better homogeneity to CBZ polymeric dispersions than the physical mixture process. In summary, we demonstrated the feasibility of obtaining a homogeneous polymeric solid dispersion of CBZ from an aqueous media by spray-drying and a clear influence of the βCD:HPMC ratio on the release profile of CBZ.