Hydrophilic matrix system of a plant extract based on co-spray-dried powders: extract release mechanisms study

GALLO LOREANA; JULIANA PIÑA; BUCALÁ VERÓNICA; ALLEMANDI DANIEL; RAMIREZ RIGO M.VERÓNICA

Rosario

Congreso; 2º Reunión Internacional de Ciencias Farmacéuticas; 2012

Universidad Nacional de Rosario-Universidad Nacional de Córdoba

Introduction: Hydrophilic matrices are one of the most widely used modified-release systems (MRS) for drug delivery. They consist of a compact containing a mixture of a drug and a hydrophilic polymer, which retard the drug release. There is yet a great potential for the development of novel herbal MRS. In particular, hydrophilic matrices based on medicinal plant extracts constitute a promising therapeutic strategy. Dried plant extracts offer numerous advantages over liquid forms. Nevertheless, these characteristics depend on the production steps. In this sense, spray-drying is a technique used to generate powders with precise quality specifications in continuous operation. The goal of this study was to develop a control-release spray dried co-processed powder based on a medicinal plant extract for matrices post-production, aiming to identify the mechanisms that modulate extract release. Materials and methods: Hamamelis virginiana was selected as a model plant extract. It is used for the treatment of chronic varicose vein disease. The components co-processed by spray-drying were: a hydrophilic polymer (Sodium carboxymethylcellulose, Na-CMC), a drying adjuvant (SiO2) and the fluid plant extract. The concentration of the spray-dried dispersion, the polymer grade and the drying operating conditions were selected in previous studies. Water uptake, radial front movements, extract release in different media (for 8h, at 50 or 100 rpm) and matrix erosion studies were carried out in order to identify the extract release mechanisms from the developed matrices. Well-known kinetic models were used to corroborate the release mechanisms. Results: The matrices showed a rapid water uptake, promoting the gel layer formation. First, swelling of the gel layer was observed. Then, a balance between expansion and erosion took place. At pH 1.2, the matrices did not release the extract completely. The Na-CMC reverted to its acidic form, which is an insoluble substance in acidic medium. Therefore, the consolidation of an insoluble layer limited the extract release. At pH 6.8, the extract release was completely due to the high solubility of Na-CMC in that medium. Matrices first exposed to pH 1.2 (2 h) and then to pH 6.8 (6 h), also released the extract completely. The release profile between 2 and 4 h was slower than that at pH 1.2 for 8 h because the insoluble acidic Na-CMC needed some time at pH 6.8 to revert from its acidic form to an erodible one. Korsmeyer kinetic model indicated that the extract diffusion and polymer erosion were involved in the extract release. According to Peppas and Sahlin model, the drug transport by erosion seemed to be more important than that by diffusion. Besides, the matrix mass loss was higher than the mass of released extract. In addition, the higher the dissolution medium agitation, the faster the extract release, being this an expected behavior for erodible matrix. Conclusions: The spray-drying was found as a good strategy to improve the functionality of medicinal plant extracts powders. The Hamamelis virginiana release took place by combined extract diffusion and matrix erosion. Moreover, the polymer erosion mechanism appeared to be the main responsible for the extract release.