Desenvolvimento de micropartículas e comprimidos microparticulados contendo piperina

Abstract

Piperine is an alkaloid extracted from plants of the Piper genus, among which is the Piper nigrum species, the black pepper, widely employed in Indian cooking and traditional medicine. Moreover, piperine exhibits important pharmacological activities, as antioxidant, antitumoral and neuroprotector, as well as improving other drugs bioavailability when associated to it. However, when orally administered, presents as an inconveniency an irritation of the gastrointestinal tract and it’s insoluble in aqueous media. Microencapsulation using ethylcellulose is an alternative to overcome this issues, since this polymer is capable of masking unpleasant tastes and control the release of the microencapsulated active ingredientes. Thus, in this study, microparticulated systems containing piperine were prepared with the ethylcellulose polymer employing emulsification-evaporation of solvent O/W method. To quantify piperine, an analytical methodology by spectroscopy in UV region was validated. The developed microparticles were characterized regarding process yield, mean particle size and particle size distribution, piperine content, encapsulation efficiency, morphology, bulk and tapped densities, evaluation of flow properties and in vitro release of the active. After, to enable microparticles administration, they were converted into tablets, with the addition of polacrilin potassium and Pullulan®, and prepared by direct compression. The microparticulated tablets were characterized regarding weight, hardness, thickness, piperine content, uniformity of content, morphology and piperine in vitro release. The microparticles obtaining process presented 97.6 ± 0.3% yield and were spherical, with 190 ± 13 μm size and Span of 1.698 ± 0.180. Encapsulation efficiency was 90.0 ± 0.9%, a piperine content of 298.3 ± 2.9 mg/g. The in vitro release demonstrated a controlled release of piperine from the microparticulated systems: in 24 h, 34.8 ± 1.6% of piperine were release, while 80.9 ± 1.5% of bulk piperine was dissolved. Bulk and tapped density, Carr’s index and Hausner ratio revealed the microparticles have excellent flow properties. Thus, to prepare the microparticulated tablets, the excipients employed were only a dissolution promotor (Kyron® T-314) and the diluent (Pullulan®). The tablets presented 99.1 ± 0.9 mg weight; thickness of 3.38 ± 0.03 mm; hardness of 3.0 ± 0.2 kgf and friability 0.4%. Piperine content was 19.7 ± 0.4 mg, close to the theoretical value. The active release from the tablets was controlled, presenting 49.4 ± 2.4 % release in 24 h and the release profile was similar to the profile release of piperine from the microparticles. With this result and the scanning electron spectroscopy, it can be seen that the microparticles remained intact after the compression. Therefore, in this study microparticles and microparticulated tablets containing piperine were developed, which presented adequate physical-chemical characteristics and release profiles in order to overcome the issues presented by piperine in its oral administration and, so, the microparticulated tablets are a promising dosage unit for this purpose.