A Preformulation Study of a New Medicine for Chagas Disease Treatment: Physicochemical Characterization, Thermal Stability, and Compatibility of Benznidazole

Abstract

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van't Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68°C (∆H, 119.71 J g(-1)), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76-319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.

Study of stability and drug-excipient compatibility of estradiol and pharmaceutical excipients

“…The temperature of the column oven was maintained at 40°C. All the samples (20 lL) were injected and analyzed at 205 nm using a UV HO CH 3 OH H H H H Fig. 1 The structure of estradiol detector.…”

“…Indeed, potential physical and chemical interactions between drug and excipients can affect the chemical nature, stability, and bioavailability of a drug and thus its effectiveness [1][2][3][4][5][6]. In the literature, two types of chemical incompatibilities have been described: (i) excipient-promoted intrinsic degradation of the drug, such as hydrolysis or oxidation and/or (ii) a covalent reaction between the drug and the excipient [5,7].…”

Preformulation characterization andin vivoabsorption in beagle dogs of JFD, a novel anti-obesity drug for oral delivery

“…But for microcrystalline cellulose with a bigger molecular structure, the steric hindrance might block the reaction with JFD's amine. Also, compared with sodium starch glycolate, the reaction of lactose and JFD is significant because the lactose has freer hydroxyl groups to be deoxidized by the drug 42 . For lubricant magnesium stearate, there are two possible reasons: one is hydrolytic ion-catalyzed degradation 43 ; the other is the possibility of the amine group on JFD reacting with the stearic acid which was produced through the interaction of magnesium stearate and the released HCl of JFD by desalting 12,44 .…”

Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

“…In vitro dissolution testing is the most important method in the development of solid dosage forms [9][10][11][12][13]. It can be used to predict the performance of a dosage form, especially when drug release is the limiting factor in the absorption process [12,14].…”

“…These parameters affect the in vivo performance of the drug, and therefore the pharmacological activity [17]. Examples of drugs that have been tested in this way, such as ayurvedic medicinal herbs [18], nateglinide [19], ketoprofen [20], benznidazole [9] and lercanidipine [21], have been reported in the literature.…”