Pedro Ros Petrovick

Secagem por aspersão (spray drying) de extratos vegetais: bases e aplicações

In Brazil, the majority of the approved phytomedicines are formulated as solid dosage forms containing plant dried extracts as active component. Spray drying technique has been widely used to obtain dried extracts presenting better technological characteristics and greater concentration of biological active constituents. Physicochemical properties of such products depend on factors related to process, formulation (inlet material) and equipment. This review presents and discusses some studies related to parameters of process and formulation, as well as some technical applications focusing on the development of dried extract from plants, mainly from the Brazilian medicinal flora.

Dry granulation and compression of spray-dried plant extracts

The purpose of this research was to evaluate the influence of dry granulation parameters on granule and tablet properties of spray-dried extract (SDE) fromMaytenus ilicifolia, which is widely used in Brazil in the treatment of gastric disorders. The compressional behavior of the SDE and granules of the SDE was characterized by Heckel plots. The tablet properties of powders, granules, and formulations containing a high extract dose were compared. The SDE was blended with 2% magnesium stearate and 1% colloidal silicon dioxide and compacted to produce granules after slugging or roll compaction. The influences of the granulation process and the roll compaction force on the technological properties of the granules were studied. The flowability and density of spray-dried particles were improved after granulation. Tablets produced by direct compression of granules showed lower crushing strength than the ones obtained from nongranulated material. The compressional analysis by Heckel plots revealed that the SDE undergoes plastic deformation with a very low tendency to rearrangement at an early stage of compression. On the other hand, the granules showed an intensive rearrangement as a consequence of fragmentation and rebounding. However, when the compaction pressure was increased, the granules showed plastic deformation. The mean yield pressure values showed that both granulation techniques and the roll compaction force were able to reduce the materials ability to undergo plastic deformation. Finally, the tablet containing a high dose of granules showed a close dependence between crushing strength and the densification degree of the granules (ie, roll compaction force).

Validation of a LC method for the analysis of phenolic compounds from aqueous extract of Phyllanthus niruri aerial parts.

A reversed-phase high-performance liquid chromatographic separation and quantitative method using a phosphoric acid-acetonitrile gradient was developed to analyze phenolic compounds present in aqueous extract from the aerial parts of Phyllanthus niruri. The chromatographic method was validated for linearity, precision and accuracy for both reference substance (gallic acid) and for three well resolved peaks from P. niruri aqueous extract. Both calibration curves were linear with correlation coefficients higher than 0.999. The reproducibility for the three peaks ranged from 2.3% to 4.6% and the accuracy for gallic acid in the aqueous extract was 103%. The method allowed the complete resolution of three peaks, one of them was identified by diode array detection as gallic acid. The analysis of the botanic morphological elements of the aerial parts from P. niruri showed that the leaves have a higher amount of phenolic compounds than the branches.

Optimization of tablets containing a high dose of spray-dried plant extract: A technical note

ConclusionsOptimization of CSD and CMC-Na in tablet formulations containing a high dose of SDE fromM ilicifolia was performed by central composite design (CCD) and response surface methodology (RSM). The study demonstrated that CSD affected mainly the hardness and friability, while CMC-Na modified the disintegration times. The optimum formula for minimum disintegration time and friability, and maximum crushing strength, was found to contain 1.2% (wt/wt) of CSD and 5.0% (wt/wt) of CMC-Na. At these conditions, the tablet shows a crushing strength of 107.9 N, a friability of 0.56% (wt/wt), and a maximum disintegration time of 6.8 minutes.

New rules for phytopharmaceutical drug registration in Brazil

Although it is among the ten largest pharmaceutical markets in the world and has the most diverse flora, few efforts have been made in Brazil in order to assure legal rules, which are able to provide phytotherapeutical products with efficacy, safety and constant quality. Only in the last 3 years has the Ministry of Health convened an expert commission to evaluate the existent legal requirements for such products and to provide modern and effective legislation. The results of this work and the consequences of its implementation are discussed in this article.

Preparation and characterization of spray-dried powders from Achyrocline satureioides (Lam.) DC extracts

Two Achyrocline satureioidesspray‐dried extracts were prepared from 80% ethanol using raw material pretreated with petroleum ether (P1) in one case and nontreated crude vegetable drug (P2) in the other case. The atomization was carried out in a Büchi 190 Mini‐spray dryer using colloidal silicon dioxide as technological carrier. The ethanol content was previously reduced to 10% (v/v) in a low pressure distillation system and the extracts were concentrated four‐fold. The nonpolar fraction was maintained in a homogeneous suspension by addition of 2% (w/w) polysorbate 80. The main flavonoids in the feed solutions and in the spray‐dried powders were assayed by HPLC and their concentrations in the final products, P1 and P2, were 99%–101%. Both spray‐dried extracts presented good physical properties (hygroscopicity, particle form and size). The results suggest that the petroleum ether treatment of raw material did not influence the technological properties of the final spray dried products.

Eudragit E as excipient for production of granules and tablets from phyllanthus niruri L spray-dried extract

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract fromPhyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2×3 factorial design, where Eudragit E concentration and compression force were the in-dependent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formuations in order to achieve less water sorption and improve the release of the extract from the tablets.

Response Surface Analysis Applied to the Preparation of Tablets Containing a High Concentration of Vegetable Spray-Dried Extract

This work relates to the formulation of tablets containing a high proportion of spray-dried extracts (SDEs) from Passiflora edulis leaves. The tablets were prepared by direct compression. Colloidal silicon dioxide was selected as a glidant and moisture adsorbent, cross-linked carboxymethycellulose was used as the disintegrant, microcrystalline cellulose was the filler/binder, and tricalcium phosphate as a spray-drying adjuvant. The colloidal silicon dioxide and cross-linked carboxymethycellulose quantities and their influences on the tablet hardness and disintegration time were studied by a central composite design. The model equations were fitted to the experimental data and then validated. It could be concluded that the colloidal silicon dioxide proportion increased the hardness, and the cross-linked carboxymethycellulose proportion determined a linear decrease of the disintegration time. The optimal values chosen were 2.0% Aerosil® 200 and 2.5% Ac-Di-Sol®. The tablets showed a hardness of 85.02 N and a disintegration time of 7.35 min.

Development and Validation of an HPLC Method for the Characterization and Assay of the Saponins from Ilex paraguariensis A. St.‐Hil (Mate) Fruits

Abstract Two improved HPLC methods for the characterization and assay of the saponin content in green fruits of Ilex paraguariensis (erva‐mate) are described. Both HPLC methods consisted of isocratic separation at room temperature, using a RP‐18 column with UV‐Vis detection. The first system was intended for the characterization of the main I. paraguariensis saponin fraction, while the second one was specifically developed and validated for its quantitation. Matesaponin‐3 was used as external standard. From the freeze dried extract, ten peaks were characterized as saponins by TLC and HPLC analysis. The matesaponin‐3 content was 5.13 g%, and the total saponin content, calculated by the sum of the areas related to the peaks previously characterized as saponins, was 30.48 g%.

A dry extract of Phyllanthus niruri protects normal cells and induces apoptosis in human liver carcinoma cells

The ability to induce apoptosis is an important marker for cytotoxic antitumor agents. Some natural compounds have been shown to modulate apoptosis pathways that are frequently blocked in human cancers, and therefore, these compounds provide novel opportunities for cancer drug development. Phyllanthus, a plant genus of the family Euphorbiaceae, exhibits multiple pharmacological actions. Of these, Phyllanthus niruri extracts exhibit significant antitumor activity, which is consistent with the traditional medicinal use of this plant. To examine the apoptotic effects of a spray-dried extract of P. niruri (SDEPN), human hepatocellular carcinoma cells (HepG2, Huh-7), colorectal carcinoma cells (Ht29) and keratinocytes (HaCaT) were exposed to the extract for 4, 8 and 24 h. Flow cytometry and caspase-3 immunostaining were used to detect apoptosis, while analysis of variance was applied to identify significant differences between groups (P < 0.05). At all timepoints, the SDEPN induced significantly different cytotoxic effects for HepG2 and Huh-7 cells compared with control cells (P < 0.001). In contrast, the SDEPN had a protective effect on HaCaT cells compared with control cells at all timepoints (P < 0.001). In caspase-3 assays, activation was detected after cell death was induced in Huh-7 and HepG2 cancer cells by the SDEPN. In combination, these results indicate that the SDEPN is selectively toxic towards cancer cell lines, yet is protective towards normal cells.