RESUMO
A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 µm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min−1. UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 ºC under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL−1; LOQ: 105 ng mL−1) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: tmax was 2.5h, Cmax was 56.5 µg mL−1, t1/2 was 8.2 h, AUC0-36 was 845.9 µg h mL−1. The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.
RESUMO
Castration refers to induced sterility via physical, chemical, or hormonal methods. Chemical castration is an efficient and reliable technique in contrast to other sterilization procedures as it is less painful to physical methods and costeffective to hormonal methods. Azadirachta indica (neem), is a charismatic plant as its leaves possess antiinflammatory, antimicrobial, and antiandrogenic chattels. To abate the escalating human population in South Asia, neem oil and neem leaf extract have been effectively used as a contraceptive agent. The key determinant of the current study was to evaluate Neem as a chemical sterilizing agent, (either necrotic or apoptotic), in dogs injected intratesticular in comparison to a hypertonic saline solution. Pre and postinjection testicular width size and blood samples for serum testosterone levels were collected on alternative days. Results disclosed substantial changes in testicular width size, histopathological profile, and serum testosterone level. A nonsignificant (P > 0.05) preinjection testicular width readings in contrast to a significant increase (P < 0.05) three days postinjection was noted in all the competitive groups. The mean values recorded for testicular width size at the end of the trial study via neem leaf extract, 30% HSS and, control groups were 27.7362 ± 2.3315mm, 30.9594 ± 4.6861mm, and 24.5023 ± 2.5387mm, respectively. A declining trend, regarding serum testosterone level being statistically significant (P < 0.05) was recorded in treated groups (A, B) in contrast to the control group (C) as the values were 1.5357 ± 0.7819ng, 1.2669 ± 0.9095ng, and 2.4517 ± 0.1827ng in groups A, B, and C, respectively. Histopathological findings advocated the presence of apoptotic bodies in the neem treated group whereas the presence of degenerated interstitial cells, necrosed seminiferous tubules, damaged germinal epithelium, and ceased spermatogenesis was also studied in both competitive groups. Thus, the apoptotic effect and antiinflammatory property of neem leaf extract resulted in less painful castration and verified Azadirachta indica as a better substitute for chemical castration in contrast to hypertonic saline solution.(AU)
A castração consiste na indução da esterilidade por meio físico, químico ou hormonal. A castração química é uma técnica eficiente e confiável, em contraste com outros procedimentos de esterilização, pois é menos dolorosa para os métodos físicos e econômicos para os métodos hormonais. Azadirachta indica (neem), é uma planta carismática, pois possui folhas antiinflamatórias, antimicrobianas e antiandrogênicas. Para diminuir a crescente população humana no sul da Ásia, o óleo de nim e o extrato de folhas de nim têm sido efetivamente usados como agente contraceptivo. O principal determinante deste estudo atual foi avaliar o Neem como um agente esterilizante químico (necrótico ou apoptótico) em cães injetados intratesticularmente em comparação com uma solução salina hipertônica. O tamanho da largura testicular pré e pósinjeção e as amostras de sangue para os níveis séricos de testosterona foram colhidas em dias alternados. Os resultados obtidos revelaram alterações substanciais no tamanho da largura testicular, perfil histopatológico e nível sérico de testosterona. Observouse uma leitura não significativa (P> 0,05) da largura testicular da préinjeção, em contraste com um aumento significativo (P <0,05) três dias após a injeção em todos os grupos competitivos.Os valores médios registrados para o tamanho da largura testicular no final do estudo via extrato de folhas de nim,HSS a 30% e grupos controle foram 27,7362 ± 2,3315 mm, 30,9594 ± 4,6861 mm e 24,5023 ± 2,5387 mm, respectivamente.Uma tendência decrescente, com relação ao nível sérico de testosterona sendo estatisticamente significante (P <0,05), foi registrada nos grupos tratados (A, B), em contraste com o grupo controle (C), pois os valores eram 1,5357 ± 0,7819ng, 1,2669 ± 0,9095ng e 2,4517 ± 0,1827ng nos grupos A, B e C, respectivamente. Os achados histopatológicos advogaram a presença de corpos apoptóticos no grupo tratado com nim, enquanto a presença de células intersticiais degeneradas, túbulos seminíferos necrosados, epitélio germinativo danificado e espermatogênese interrompida também foi estudada nos dois grupos competitivos. Assim, o efeito apoptótico e a propriedade antiinflamatória do extrato de folhas de nim resultaram em uma castração menos dolorosa e confirmaram que a Azadirachta indica foi um melhor substituto para a castração química do que a solução salina hipertônica.(AU)