This study aimed to develop a reliable stability-indicating method (SIM) for amoxicillin 500 mg capsules (DP-drug product). A literature review addressing amoxicillin (AMX; DS-drug substance) forced degradation studies and the existing SIMs was conducted to verify the most significant outcomes. Subsequently, the forced degradation of DP and DS was carried out following the Brazilian Health Surveillance Agency (ANVISA) guidelines, including thermal degradation (dry and wet heat), acidic and alkaline hydrolyses, hydrogen peroxide oxidation, reaction with copper, and photodegradation. Both DS and DP were more susceptible to 0.015 M NaOH, resulting in approximately 50% degradation. AMX DS and DP were not significantly photodegraded, but some degradation products (PDegs) showed susceptibility to light exposure. Thermodegraded samples showing ≥ 10% degradation exhibited modified profiles in thermogravimetric (TG) and differential scanning calorimetric (DSC) analyses. The X-ray powder diffraction patterns (XRPD) of DS samples exposed to dry and wet heat displayed complete amorphization of AMX, attesting to the occurrence of physical degradation concomitantly with chemical degradation, which can alter the drug’s bioavailability. In contrast, the thermodegraded DP samples exhibited intact AMX crystals interspersed with the amorphous form, perhaps partly protected by the excipient. The validated SIM was able to detect and quantify about 80 PDegs.

Um total de 105 amostras clínicas de micoplasma, originárias de caprinos, e uma de ovino foram investigadas quanto a presença de plasmídios, que foram observados em trinta e três (31%) delas. Esses micoplasmas provieram de 13 rebanhos. Dez desses rebanhos eram sintomáticos para micoplasmose (mastite, poliartrite, septicemia) e três eram assintomáticos, i.é., clinicamente sadios. Vinte e oito amostras eram Mycoplasma mycoides subespécie mycoides LC ("large colony" ou biotipo caprino), quatro eram M. capricolum subsp. capricolum e uma era M. cottewii. Os plasmídios foram linearizados com endonucleases EcoRI, EcoRV, EcoRI e EcoRV ou BamHI e EcoRV e apresentaram cinco tamanhos (1,1; 1,6; 1,7; 1,8 e 1,9 Kbp). Com base na digestão pela enzima de restrição e o tamanho dos DNA extracromossomais, cinco tipos de plasmídio foram encontrados (p1II, p2III, p2V, p3I e p4IV). O reduzido tamanho desses DNA circulares muito provavelmente exclui formas replicativas de vírus DNA, cujo tamanho é igual ou maior que 8,0 Kbp.

One-hundred-five (105) clinical isolates of mycoplasma from caprine origin and one isolate from ovine were surveyed for plasmids, which were present in thirty-three (31%) of them. These mycoplasmas originated from 13 herds. Ten of them were symptomatic for mycoplasmal disease (mastitis, polyarthritis, septicemia) and three herds were asymptomatic, i.e., clinically normal. Twenty-eight isolates were Mycoplasma mycoides subspecies mycoides LC (large colony or caprine biotype), four were Mycoplasma capricolum subsp. capricolum and one was Mycoplasma cottewii. The isolated plasmids were linearized by EcoRI, EcoRV, EcoRI and EcoRV or BamHI and EcoRV, and were of five sizes (1.1, 1.6, 1.7, 1.8, and 1.9 Kbp). Based on restriction enzyme digestion and size of the linearized supercoiled extrachromosomal DNA, five plasmid types were recovered (p1II, p2III, p2V, p3I, and p4IV). The small size of these DNA elements probably exclude replicative forms of DNA virus, which are equal or larger than 8.0 Kbp.