Elionai Cassiana de Lima Gomes

Thermal analysis applied to verapamil hydrochloride characterization in pharmaceutical formulations.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are useful techniques that have been successfully applied in the pharmaceutical industry to reveal important information regarding the physicochemical properties of drug and excipient molecules such as polymorphism, stability, purity, formulation compatibility among others. Verapamil hydrochloride shows thermal stability up to 180 °C and melts at 146 °C, followed by total degradation. The drug is compatible with all the excipients evaluated. The drug showed degradation when subjected to oxidizing conditions, suggesting that the degradation product is 3,4-dimethoxybenzoic acid derived from alkyl side chain oxidation. Verapamil hydrochloride does not present the phenomenon of polymorphism under the conditions evaluated. Assessing the drug degradation kinetics, the drug had a shelf life (t90) of 56.7 years and a pharmaceutical formulation showed t90 of 6.8 years showing their high stability.

Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica

Several matters of the pharmaceutical demonstrate the great importance of thermal analysis application, especially TG and DSC for the pharmaceutical industry future, namely: characterization of the drugs with the thermal events definition, in studies of drug purity, in the polymorphs identification, in compatibility studies of solid dosage pharmaceutical formulations, in drugs and pharmaceutical formulations thermal stability, and in determination of shelf life for isothermal degradation kinetics by extrapolation using the Arrhenius equation. Thus, the test results obtained from thermal analysis are directly related to the quality of a pharmaceutical product, whether the stability or bioavailability of the pharmaceutical product.

ANÁLISE TÉRMICA APLICADA À CARACTERIZAÇÃO DA SINVASTATINA EM FORMULAÇÕES FARMACÊUTICAS

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for drugs characterization, purity, formulations compatibility, polymorphism identification, stability evaluation, and thermal decomposition of drugs and pharmaceutical formulations. Simvastatin showed fusion at 138.5 oC and thermal stability up to 248 oC. Simvastatin was incompatible with preservative excipient butylhydroxyanisole (BHA) performing a process of crystal amorphization. The drug showed morphological polymorphism, where it has the same unit cell but with different crystal habits according to the recrystallization solvent.

Thermal behavior study and decomposition kinetics of amiodarone hydrochloride under isothermal conditions

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are useful techniques that have been successfully applied in the pharmaceutical industry to reveal important information regarding the physicochemical properties of drugs and excipient molecules, such as polymorphism, stability, purity, formulation compatibility, among others. AMI presents a thermal stability of up to 431 K and a fusion onset temperature of 432 K. The drug has proven to be incompatible with magnesium stearate, eskis red pigment, and yellow iron oxide. In the present study, this drug presented degradation upon undergoing basic hydrolysis and oxidation; the degradation product produced under basic hydrolysis is 2-butyl-3-benzofuranyl-3,4-dihydroxy-5-iodophenylketone. Assessing the degradation kinetics, the drug presented a shelf life (t90) of 43 years, while a pharmaceutical formulation showed a t90 of 1.7 years, which is consistent with commonly understood incompatibilities in pharmaceutical formulations.

Bevacizumab-loaded polyurethane subconjunctival implants: effects on experimental glaucoma filtration surgery.

PURPOSE Vascular endothelial growth factor (VEGF) may contribute to the scarring process resulting from glaucoma filtration surgery, since this cytokine may stimulate fibroblast proliferation. The aim of this study was to describe a new bevacizumab-loaded polyurethane implant (BPUI) and to evaluate its effectiveness as a new drug delivery system of anti-VEGF antibody in a rabbit model of glaucoma filtration surgery. METHODS An aqueous dispersion of polyurethane was obtained via the conventional process. Bevacizumab (1.5 mg) was then incorporated into the dispersion and was subsequently dried to form the polymeric films. Films with dimensions of 3×3×1 mm that either did (group BPUI, n=10) or did not contain bevacizumab (group PUI, n=10) were implanted in the subconjunctival space, at the surgical site in 1 eye of each rabbit. The in vitro bevacizumab release was evaluated using size-exclusion high-performance liquid chromatography (HPLC), and the in vivo effects of the drug were investigated in a rabbit experimental trabeculectomy model by examining the bleb characteristics and collagen accumulation, and by performing immunohistological analyses of VEGF expression. RESULTS HPLC showed that only 10% of the bevacizumab in the implants had been released by postoperative day 5. In vivo studies demonstrated that the drug had no adverse effects; however, no significant differences in either the bleb area score or the collagen deposit intensity between the group PUI and the group that BPUI were observed. Moreover, the group BPUI presented a significantly lower proportion of VEGF-expressing fibroblasts than group PUI (0.17±0.03 vs. 0.35±0.05 cells/field, P=0.005). CONCLUSIONS This study demonstrated that bevacizumab release from the BPUIs only occurred for a short time probably from the surface of the films. Nevertheless, they were well tolerated in rabbit eyes and reduced the number of VEGF-expressing fibroblasts.

Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz.

Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

Friedelin molecular conformers were obtained by Density Functional Theory (DFT) and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single-crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer.

Development and validation of a high performance liquid chromatographic method for determination of cyclosporine-A from biodegradable intraocular implants

C and UV detection at 210 nm. The method provided selectivity based on resolution among peaks. It was linear over the range of 2.5-40.0 µg/mL. The quantitation and detection limits were 0.8 and 1.2 µg/mL, respectively. The recovery was 101.8% and intra-day and inter-day precision was close to 2%.

Desenvolvimento e validação de método analítico para quantificação do fármaco bevacizumabe por cromatografia a líquido de alta eficiência

In this study, an analytical method was developed and validated for quantitation of the drug bevacizumab (Avastin®) by high performance liquid chromatography (HPLC). The HPLC column was a BioSuite 250® HR SEC, 300 x 7.8 mm x 5 µm (Waters, USA). The mobile phase consisted of phosphate buffered saline (PBS). The results revealed that the method was specific, precise, accurate, robust and linear (r2 = 0.998) from 5 to 75 µg mL-1. Therefore, this method can be used in drug release studies or in quality control ampoules of the drug.

Physicochemical characterization, the Hirshfeld surface, and biological evaluation of two meloxicam compounding pharmacy samples

Meloxicam (MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently between samples. The FTIR and 1H NMR spectra showed characteristic assignments. 13C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph III in an experimental model of acute inflammation in mice. Our results highlighted the need for complete crystallographic characterization and the separation of freely used raw materials in compounding pharmacies, as a routine procedure, to ensure the desired dose/effect.