Marcelo Antonio de Oliveira

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.

Degradation Kinetics of Atorvastatin under Stress Conditions and Chemical Analysis by HPLC

Atorvastatin is an antilipemic drug belonging to the statins class, whose reference drug is Pfizer’s Lipitor®. It is used to reduce the levels of lipoproteins rich in cholesterol and reduce the risk of coronary artery disease. It is well-known that calcium atorvastatin (ATV), C66H68CaF2N4O10•3H2O, presents polymorphism. The drug in question is commonly sought after by pharmaceutical industries that produce generic drugs, due to the fact that the drug has a high value price, it is consumed globally, and its patent expired in late 2010. Many questions concerning this drug’s pharmaceutical scope demonstrate its importance regarding stability studies and the identification of degradation products of drugs and pharmaceutical formulations. ATV has been found to degrade under acid and basic conditions, including a first order kinetic degradation under acid conditions, as compared to a zero order kinetic degradation under basic conditions, which tends to be less stable when studied within acid mediums. The rate constant (k) for degradation in acid medium was 1.88 × 10−2 s−1 (first order), while for basic medium k = 2.35 × 10−4 mol L−1 s−1 (zero order), demonstrating a lower stability of the drug within acid mediums.

Risk of Soil Recontamination Due to Using Eleusine coracana and Panicum maximum Straw After Phytoremediation of Picloram

This study aimed to evaluate the herbicidal activity of picloram on the biomass of the remediation plants Eleusine coracana and Panicum maximum after cultivation in a soil contaminated with this herbicide. These species were grown in three soils, differentiated based on texture (clayish, middle, and sandy, with 460, 250, and 40 g kg–1 of the clay, respectively), previously contaminated with picloram (0, 80, and 160 g ha–1). After 90 days, the plants were harvested and an extract was produced by maceration of leaves and stems of these plants. It was applied to pots containing washed sand, comprising a bioassay in a growth chamber using soybean as a bioindicator for picloram. Soil and plant samples were analyzed by HPLC. The results showed the presence of picloram or metabolites with herbicidal activity in the shoots of E. coracana and P. maximum at phytotoxic levels with regard to soybean plants, indicating that they work only as phytoextractors and that the presence of straw on the soil surface can promote recontamination within the area. It is not recommended to cultivate species susceptible to picloram in areas where it was reported remediation by E. indica and P. maximum and still present residues of these species.

Developing methods to compare tablet formulations of atorvastatin

Atorvastatin (ATV) is an antilipemic drug of great interest to the pharmaceutical industry. ATV does not appear in the monographs of Brazilian pharmacopoeia, and analytical methodologies for its determination have been validated. The chromatographic conditions used included: RP-18 column-octadecylsilane (250 x 4.6 mm, 5 mm), detection at 238 nm, mobile phase containing 0.1% phosphoric acid and acetonitrile (35:65% v/v), flow at 1.5 mL min-1, oven temperature at 30oC, and injection volume of 10 mL. ATV is classified as a class II product, according to the biopharmaceutical classification system. As such, a dissolution test was proposed to evaluate pharmaceutical formulations on the market today, under the following conditions: water as a dissolution medium, 1000 mL as a volume, paddle apparatus at a rotation speed of 50 rpm, 80% (Q) in 15 minutes with UV spectrophotometer readings at 238 nm. In the pattern condition proposed as the ideal dissolution test, which appropriately differentiates amongst formulations, the generic product was not considered pharmaceutically equivalent; however, in other less differential dissolution methods, which also fall within appropriate legal parameters, this product could come to be regarded as generic.

Evaluation of physicochemical properties as supporting information on quality control of raw materials and veterinary pharmaceutical formulations

This study aimed to show that the physicochemical proprieties obtained by Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG), and scanning electronic microscopy (SEM) can be useful tools for evaluating the quality of active pharmaceutical ingredients (APIs) and pharmaceutical products. In addition, a simple, sensitive, and efficient method employing HPLC-DAD was developed for simultaneous determination of lidocaine (LID), ciprofloxacin (CFX) and enrofloxacin (EFX) in raw materials and in veterinary pharmaceutical formulations. Compounds were separated using a Gemini C18 (250 mm × 4.6 mm, 5 µm) Phenomenex® column, at a temperature of 25 °C, with a mobile phase containing 10 mM of phosphoric acid (pH 3.29): acetonitrile (85.7:14.3, v/v) and a flow rate of 1.5 mL/min. Physicochemical characterization by TG, FTIR, and SEM of raw materials of LID, CFX, and EFX provided information useful for the evaluation, differentiation, and qualification of raw materials. Finally, the HPLC method was proved to be useful for evaluation of raw material and finished products, besides satisfying the need for an analytical method that allows simultaneous determination of EFX, CFX, and LID, which can also be extended to other matrices and applications.

Drug-excipient compatibility assessment of solid formulations containing meloxicam

ABSTRACT Meloxicam (MLX) is a non‐steroidal anti‐inflammatory cyclooxygenase (COX) inhibitor that is used to relieve inflammation and pain. MLX has a preferential affinity for COX‐2, which is associated with a lower incidence of gastrointestinal side effects. The drug belongs to Class II of the Biopharmaceutical Classification System (BCS) in which dissolution is the limiting step of its bioavailability. In view of this classification, carrying out further studies regarding the compatibility of MLX with excipients and the mechanisms and kinetics of its degradation reactions is fundamental because any changes would directly influence the quality of the product. The aim of the present work is to evaluate solid pharmaceutical formulations containing MLX found on the market to define the more suitable excipients to improve the stability of the pharmaceutical formulations. Thermal analysis techniques were used to characterize and evaluate the compatibility between the drug and the excipients present in the market formulations. In the evaluation of its solid‐state kinetics, MLX raw material under inert conditions had a shelf life of approximately 6 years. In the study of compatibility between the drug and excipients, MLX was found to be incompatible with magnesium stearate after DSC analysis under binary mixtures, which was confirmed by stress studies and chromatographic analyzes. Graphical abstract Figure. No Caption available.

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.