Development and validation of an analytical method by UV spectrophotometry for the quantitative determination of the anti-neoplastic β-lapachone

A β-lapachona é uma ortonaftoquinona natural extraída de plantas da família Bignoniaceae, como o Ipê Roxo (Tabebuia avellanedae Lor), árvore nativa do Brasil, ou sintetizada a partir de seu isômero lapachol. A β-lapachona têm demonstrado uma série de ações farmacológicas incluindo antibacteriana, antifúngica, tripanossomicida, antiviral e antineoplásica. Não há relatos na literatura de um método analítico espectrofotométrico para a quantificação de β-lapachona. Assim, o presente trabalho descreve o desenvolvimento de um método simples, econômico, rápido e preciso por espectrofotometria para a quantificação deste fármaco. O método desenvolvido consiste na solubilização da β-lapachona em álcool etílico com posterior diluição no sistema de solventes álcool etílico:água para quantificação em ultravioleta (λ = 256 nm). O método foi validado segundo parâmetros descritos pela International Conference on Harmonization (Q2A/Q2B) e Agência Nacional de Vigilância Sanitária (ANVISA) RE 899/03. Os resultados da validação mostram que o método é robusto, linear, sensível, preciso e exato dentro dos parâmetros avaliados.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Simultaneous determination of antiretroviral zidovudine, lamivudine and efavirenz by RP HPLC-DAD

A reverse phase high-performance liquid chromatography-photodiode array detector (RP HPLC-DAD) method for simultaneous determination of lamivudine (3TC), zidovudine (AZT), two nucleoside reverse transcriptase inhibitors, and efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, in tablets is described. The drugs separation was performed on a C18 column (250 x 4,6 mm, 5 μm - Phenomenex®), through a mobile phase drag composed by a binary gradient of acetonitrile and water HPLC grade. The drugs detection was performed at 248 nm, resulting in a 14 min chromatographic run. The samples were prepared by crushing tablets, weighing powder, diluting it by a 10 min sonication and filtrating solution, resulting in samples with final concentration of 20, 40 e 40 μg.mL–1 of 3TC, AZT and EFV, respectively. The method was adequate for quality control purposes and was validated following the ICH guidelines.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Dermoid and epidermoid cysts of the oral cavity : a 48-year retrospective study with focus on clinical and morphological features and review of main topics

Dermoid and epidermoid cysts are slow-growing, benign developmental cysts that arise from ectodermal tissue and can occur anywhere in the body. Less than 7% of these cysts involve the head and neck region, with only 1.6% of cases presenting in the oral cavity. To evaluate the clinical and histopathological features of dermoid (DCs) and epidermoid (ECs) cysts stored in the archives of a referred Oral Pathology Service over a 48-year-period, and to review current concepts about these cysts. All DCs and ECs were reviewed, and clinical data were obtained from the patient records. Fourteen cases of DCs and thirteen cases of ECs were re-evaluated microscopically by 2 oral pathologists. Among 15.387 cases, 14 (0.09%) had a histopathological diagnosis of DCs and 13 (0.08%) of ECs. For DCs, ten (71.4%) patients were women, with the mean age of 37.2 years. All DCs were lined by a stratified squamous epithelium (100%), with gut and respiratory epithelium observed in 1 (7.1%) and 2 (14.3%) cases, respectively. Chronic inflammatory cells, melanin, multinucleated giant cell reaction, and Pacini bodies were also observed. For ECs, eight (61.5%) cases were in women, and the mean age was 38.2 years. All ECs were lined by a stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, and adipose tissue were observed in the fibrous capsule. Our results suggest that stratified squamous epithelium is the predominant epithelial lining of these cystic lesions. Also, we may find some unusual findings in DCs, such as Pacini bodies

Pharmaceutical development of paracetamol oral suspension

The aims of this work are obtaining and evaluating paracetamol oral suspension 32 mg/mL by qualitative and quantitative planning of the ingredients. The observations of the physical-chemical formulations were based in comparison with the specifications of paracetamol solution contained in the Brazilian Pharmacopoeia and editing with some analysis on the same reference drug (Tylenol® child 32 mg / mL). We sought to develop a low cost and good quality formulation, acceptable to the children's market, since the suspension dosage form is characterized by disguising the unpleasant taste of drugs. The chosen formulation showed good rheology properties, excellent sensory and values of pH, viscosity, density and content within the pharmacopoeia specifications. We obtained a satisfactory formulation, with smaller amount of excipients in relation to the reference product, which can be used by diabetics and is compatible with the official specifications, with respect to physical-chemical tests performed.Colegio de Farmacéuticos de la Provincia de Buenos Aire

New alternative analytical to quantify the anti-leprosy drug dapsone by UV spectrophotometry

Dapsone is the drug of choice for leprosy treatment. Despite the existence of previous analytical methods, this study aimed to develop a new analytical alternative for dapsone quantification by UV spectrophotometry. Since the pharmacopeial method uses methanol, a toxic solvent, the method was developed using first dilution in ethanol (500 μg/mL) and second dilution in water (5 μg/mL), with quantification in 295 nm. For validation, the specificity was confirmed by quantification of degraded samples using the developed method in comparison with a second analytical technique (HPLC-DAD). The proposed method proved to be specific, linear, precise, accurate and robust, with analytical low cost and toxicity, besides presenting operational ease.Colegio de Farmacéuticos de la Provincia de Buenos Aire

HPLC-DAD analysis, antinociceptive and anti-inflammatory properties of the ethanolic extract of Hyptis umbrosa in mice

Hyptis umbrosa (syn. Mesosphaerum sidifolium) (Lamiaceae Family) has been used to treat several conditions such as gastrointestinal disorders, skin infections, nasal congestion, fever and cramps. The objective of this study was to evaluate the chemical composition, analgesic and anti-inflammatory profiles of ethanol extract from leaves of Hyptis umbrosa (EEB). HPLC-DAD was used to determine the fingerprint chromatogram of the extract. Male Swiss mice were orally pretreated with EEB (100, 200 or 400 mg/kg; 60 min before initiating algesic stimulation) and antinociceptive activity was assessed using the acetic acid-induced writhing model, formalin test and hyperalgesia induced by glutamate or capsaicin. Also, peritonitis was induced by the intrathoracic injection of carrageenan to quantify the total number of leukocytes. The presence of phenolic compounds in the extract was confirmed using HPLC-DAD. The treatment with EEB, at all doses, produced a significant analgesic effect against acetic acid-induced antinociceptive activity. In the formalin test, only the 400-mg/kg-dose of EEB had a significant effect in the first phase. However, all doses tested were able to reverse nociception in the second phase. The effect of all doses of EEB also showed a significant antinociceptive effect in the glutamate and capsaicin tests and inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. The present study suggests that the EEB possesses peripheral analgesic action and showed potential in reducing the spreading of the inflammatory processes. Also, it seems to be related with vanilloid and glutamate receptors

Ultrastructural aspects of cranial and peripheric nerves of cronically diabetic and malnourished rats: a short biochemical panorama

Diabetes Mellitus is one of the most common causes of neuropathies, which can be caused by molecular imbalances that impair metabolic pathways. Studies in rats showed the importance of sirtuins (SIRT), deacetylases that use NAD+ as a cofactor, which have a widespread function in metabolism, and their relation when food deprived or calorie restricted. Additionally, diabetic neuropathy presents different structural biomarkers that cause morphological alterations in fibers that can be partially treated. SIRT1 is the principal sirtuin, which acts on hypothalamus, liver, kidney, among other organs, up regulating or down regulating the expression of some genes or enzymes crucial in the process of glucose absorption

Influence of particle size on appearance and in vitro efficacy of sunscreens

Nanotechnology applies to diverse sectors of science. In cosmetic area, investments have strengthened the idea that nanoproducts provide innumerable benefits to consumers. Extreme exposition to solar light can cause undesirable effects, thus, adding UV filters in cosmetic products are often used as prevention. Ethylhexyl methoxycinnamate and benzophenone-3 are UV filters widely used in sunscreen formulations, this UV filters absorb UVB and UVA radiation, respectively. In this study, sunscreen formulations were developed as nano and macroemulsion, but composed by the same raw material. Nanoemulsion was obtained by phase inversion temperature method (PIT). Physical and functional properties were evaluated by visual analysis, particle size distribution and by diffuse reflectance spectrophotometry. Achieved nanoemulsion showed bluish brightness aspect, less apparent consistency than macroemulsion, stability longer than 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) sizes around 10 nm (61%) and 4.5 µm (39%). Macroemulsion showed milky aspect, higher consistency than nanoemulsion, instability after 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) size around 202 nm (9%) and 10.4 µm (91%). Effectiveness profile of sunscreen formulations remained apparently similar, based on achieved results of in vitro SPF, UVA/UVB ratio and critical wavelength assays

Brazilian Morus nigra

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats

Gelatinous capsules of B-lapachone for anti-cancer therapies

B-lapachona é uma ortonaftoquinona natural do ipê roxo crescente principalmente no Brasil, obtida também pelo processo de semissíntese do seu isômero Lapachol. É um produto vegetal simples que tem demonstrado excelente potencial antineoplásico em estudos realizados em ratos albinos, camundongos e culturas celulares. Atua por um mecanismo particular de apoptose contra diversos tipos de câncer, em especial algumas linhagens de próstata refratárias aos tratamentos convencionais. Por possuir baixa solubilidade em água, o desenvolvimento de uma forma farmacêutica a base de B-lapachona que proporcione biodisponibilidade favorável é um ponto fundamental para a continuidade das pesquisas com este ativo. Cápsulas gelatinosas duras contendo 250 mg de B-lapachona e cápsulas gelatinosas mole contendo 30 mg de B-lapachona foram desenvolvidas. Devido à forma cristalina e caráter lipofílico da B-lapachona, as cápsulas gelatinas duras não apresentaram teor de dissolução aceitável, no entanto, as cápsulas gelatinosas mole apresentaram resultados satisfatórios para continuidade dos estudos com este ativo.B-lapachone is a natural ortonaftoquinona of ipe purple growing mainly in Brazil, also obtained by the process of semi-synthesis of its isomer lapachol. It is a simple plant product that has demonstrated excellent potential in antineoplastic studies in albino rats, mice and cell cultures. Works by a particular mechanism of apoptosis against various types of cancer, especially some strains of prostate refractory to conventional treatments. It has low solubility in water, the development of a pharmaceutical form the basis of B-lapachone providing favorable bioavailability is a key point for the continuity of research with this asset. Hard gelatine capsules containing 250 mg of B-lapachone and soft gelatine capsules containing 30 mg B-lapachone were developed. Due to the crystalline form and character of lipophilic B-lapachone, the hard gelatin capsules did not show acceptable levels of dissolution, however, the soft gelatinous capsules showed satisfactory results for continuation of studies in this activeColegio de Farmacéuticos de la Provincia de Buenos Aire