Effect of physical stimuli on hair follicle deposition of clobetasol-loaded Lipid Nanocarriers

Clobetasol propionate (CLO) is a potent glucocorticoid used to treat inflammation-based skin, scalp, and hair disorders. In such conditions, hair follicles (HF) are not only the target site but can also act as drug reservoirs when certain formulations are topically applied. Recently, we have demonstrated nanostructured lipid carriers (NLC) containing CLO presenting epidermal-targeting potential. Here, the focus was evaluating the HF uptake provided by such nanoparticles in comparison to a commercial cream and investigating the influence of different physical stimuli [i.e., infrared (IR) irradiation (with and without metallic nanoparticles-MNP), ultrasound (US) (with and without vibration) and mechanical massage] on their follicular targeting potential. Nanosystems presented sizes around 180 nm (PdI < 0.2) and negative zeta potential. The formulation did not alter skin water loss measurements and was stable for at least 30 days at 5 °C. Nanoparticles released the drug in a sustained fashion for more than 3 days and increased passively about 40 times CLO follicular uptake compared to the commercial cream. Confocal images confirmed the enhanced follicular delivery. On the one hand, NLC application followed by IR for heat generation showed no benefit in terms of HF targeting even at higher temperatures generated by metallic nanoparticle heating. On the other hand, upon US treatment, CLO retention was significantly increased in deeper skin layers. The addition of mechanical vibration to the US treatment led to higher follicular accumulation compared to passive exposure to NLC without stimuli. However, from all evaluated stimuli, manual massage presented the highest follicular targeting potential, driving more than double the amount of CLO into the HF than NLC passive application. In conclusion, NLC showed great potential for delivering CLO to HF, and a simple massage was capable of doubling follicular retention

DESENVOLVIMENTO E VALIDAÇÃO DE MÉTODO ANALITICO PARA QUANTIFICAÇÃO DO VORICONAZOL EM CÓRNEA

Introdu&ccedil;&atilde;o e objetivos: O voriconazol (VOR) &eacute; um novo antif&uacute;ngico da classe tiazol de amplo espectro1 e, sua administra&ccedil;&atilde;o t&oacute;pica visa o tratamento de ceratites f&uacute;ngicas. Entretanto, o desenvolvimento de novas formula&ccedil;&otilde;es se faz necess&aacute;rio para aumentar a biodisponibilidade ocular do f&aacute;rmaco. Para este prop&oacute;sito, &eacute; necess&aacute;rio o desenvolvimento de m&eacute;todos de quantifica&ccedil;&atilde;o e extra&ccedil;&atilde;o do f&aacute;rmaco em c&oacute;rnea su&iacute;na. Desta forma, o objetivo foi desenvolver e validar um m&eacute;todo anal&iacute;tico capaz de quantificar o VOR na c&oacute;rnea. Metodologia: VOR foi quantificado por CLAE -UV (255 nm), com fase m&oacute;vel constitu&iacute;da por acetonitrila e &aacute;gua (50:50) e fluxo de 1,0 mL/min. O m&eacute;todo foi validado de acordo com os par&acirc;metros do FDA2. Para a recupera&ccedil;&atilde;o do VOR, as amostras brancas da c&oacute;rnea formam contaminadas com diferentes solu&ccedil;&otilde;es de VOR, secas e extra&iacute;das com metanol, ap&oacute;s agita&ccedil;&atilde;o 60 min em chapa magn&eacute;tica. Resultados e discuss&otilde;es: O m&eacute;todo se mostrou especifico (n&atilde;o apresentando picos interferentes no tempo de reten&ccedil;&atilde;o do VOR), linear (y=19,084x + 2,107, r2= 0,999), preciso e exato (precis&atilde;o e exatid&atilde;o inferior a 5%). A recupera&ccedil;&atilde;o do VOR na c&oacute;rnea foi de 84,79% (&plusmn; 1,34%) para concentra&ccedil;&atilde;o te&oacute;rica de 20 mg/mL e 86,09% (&plusmn; 6,20%) para concentra&ccedil;&atilde;o de 5 mg/mL. Conclus&otilde;es: O m&eacute;todo anal&iacute;tico foi validado e o m&eacute;todo de recupera&ccedil;&atilde;o mostrou-se eficaz para quantifica&ccedil;&atilde;o do VOR na c&oacute;rnea

Prevalence of tablet splitting in a Brazilian tertiary care hospital

Background: Although a highly common practice in hospital care, tablet splitting can cause dose variation and reduce drug stability, both of which impair drug therapy. Objective: To determine the overall prevalence of tablet splitting in hospital care as evidence supporting the rational prescription of split tablets in hospitals. Methods: Data collected from inpatients’ prescriptions were analyzed using descriptive statistics and used to calculate the overall prevalence of tablet splitting and the percentage of split tablets that had at least one lower-strength tablet available on the market. The associations between the overall prevalence and gender, age, and hospital unit of patients were also assessed. The results of laboratory tests, performed with a commercial splitter, allowed the calculation of the mass loss, mass variation, and friability of the split tablets. Results: The overall prevalence of tablet splitting was 4.5%, and 78.5% of tablets prescribed to be split had at least one lower-strength tablet on the market. The prevalence of tablet splitting was significantly associated with the patient’s age and hospital unit. Laboratory tests revealed mean values of mass loss and variation of 8.7% (SD 1.8) and 11.7% (SD 2.3), respectively, both of which were significantly affected by the presence of coating and scoreline. Data from laboratory tests indicated that the quality of 12 of the 14 tablets deviated in at least one parameter examined. Conclusions: The high percentage of unnecessary tablet splitting suggests that more regular, rational updates of the hospital’s list of standard medicines are needed. Also, inappropriate splitting behavior suggests the need to develop tablets with functional scores