Desenvolvimento e avaliação de pellets contendo extrato de Pothomorphe umbellata (pariparoba) via extrusão esferonização

• Autor(a) principal: Araújo Júnior, César Aparício de
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000009t4j
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3745
• topic: Pothomorphe umbellata; 4-nerolidicatecol; Fotoestabilidade; Pellets; 4-nerolidylcatechol; Photostability; Photostability; Pellets; CIENCIAS BIOLOGICAS::FARMACOLOGIA

Pothomorphe umbellata (L.) Miq. Piperaceae is known in Brazil as "caapeba", "caapeba North" or "Pariparoba" being widely used as an analgesic, anti-inflammatory and antispasmodic. According to scientific studies, 4-nerolidylcatechol (4-CN) is the main secondary metabolite of P. umbellata, has antioxidant activity greater than that of vitamin E. The incorporation of the extracts of P. umbellata (L.) Miq. in solid dosage forms is an interesting strategy to enable its use as an oral antioxidant and stabilizing its active labile 4-NC. Pellets are oral dosage forms which have good flow properties due to their spherical shape, narrow size distribution, in addition, the pellets allow to obtain uniform dispersion of doses of drug and incorporation of large amounts of active substances incompatible in the same pharmaceutical form. The objective of this study was to obtain an extract of P. umbellata, develop and characterize a multi-particulate solid dosage form and evaluate the stability of the developed formulations containing 4-NC. The roots of the plant material of P. umbellata was subjected to analysis of content, residual moisture, determination of swelling index, total ash content and granulometric determination. The identification of plant constituents of the sample was made by thin layer chromatography (TLC). Obtaining the hydroalcoholic extract was made by percolation. Quantitation of 4-NC was performed by High Performance Liquid Chromatography (HPLC-UV-Vis). The analytical method was validated for the parameters required in Resolution N°. 899, ANVISA. The determination of antioxidant activity of the isolated 4-NC and the percolated was evaluated using UV-Vis spectrophotometer using a technique that measures the activity of scavenging free radical 2,2-diphenyl-1-picril-hydrazyl (DPPH •). The pellets were produced by extrusion technique / spheronisation using granulation liquid consisting of the percolated, colloidal silicon dioxide and polysorbate 80. The excipients were microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC). The drying of the pellets was done in an oven and fluidized bed coating. HPMC, povidone and copolymer (polyvinyl alcohol polyethylene glycol graft copolymer) were tested in the polymer coating. Accelerated photostability study was performed according to standards described by the ICH International Conference on Harmonisation evaluating 4-NC degradation in the extraction solution (percolated) and the solid dosage form (uncoated and coated pellets). The pellets were characterized by size distribution, morphology and friability. The external morphology of the pellets was evaluated through a stereomicroscope and the thickness of the coating was observed by Scanning Electron Microscopy (SEM). The result obtained for the moisture content was 6.33 ± 0.305% for total ash content: 8.25% ± 0.61 and swelling index of 3.30 ± 0.87mL and an average particle size of the powder was 170.26μm. The analytical method for 4-NC was linear in the range 10 to 200µg/mL. LQ and LD were calculated 1.42 and 0.42 µg/mL. The accuracy showed less than 5.0% relative standard deviation (RSD). The percolation process was efficient in the extraction of 4-NC. The production of pellets from the extrusion technique/spheronisation was presenting a satisfactory product was uniform with an average size of 1000 μm. In the study of antioxidant activity, the effective concentration (EC50) value found for the isolated 4-NC and present in the percolated was about two times more potent than vitamin E. In the study of photostability of 4-NC present in the coated pellets, the copolymer coating was used in which offered more protection to the active 4-NC against photodegradation. Given the impossibility of obtaining solid dosage forms with pure active, the use of the extract containing the 4-NC is considered more advantageous since the pharmaceutical technology can improve the stability of the asset against degradation.