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South-American Symposium on Microencapsulation

Limeira, Brazil, April 30-May 2012

PRESENTATION OUTLINE

1- Herbal Medicinal Products (HMP)

2- Drying/encapsulation of herbal preparations

3- Novel encapsulation technologies for herbal

products

4- Closing remarks

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1- Herbal Medicinal Products (HMP)

* Important for pharmaceutical research and for drug development

- Herbal medicine (Phytomedicine)

- Source of therapeutic agents

- Models molecules for synthesis of new drugs.

- Raw material for extraction of chemical precursors

* Food and cosmetic sectors

- Natural antioxidants and antiaging systems

- Natural preservatives

- Natural colouring and flavorizing agents

- Nutraceuticals (functional foods)

1.1- HMP are susceptible to natural variations

- environment,

- harvesting period,

- post-harvest processing, such as drying and storage conditions (mainly

temperature and relative humidity).

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2- Drying/encapsulation of herbal preparations

A way of standardize dosage and increasing safety of

herbal preparations.

Powdered herbal preparations: Resulted from the drying

of a concentrated crude or purified extractive solutions from

herbal materials (leaves, roots, seeds, whole plant,

inflorescence, etc.).

- Addition of carriers is almost mandatory.

2.1 Advantages

- High concentration of bioactive compounds

- Reduction in volatile losses

- Taste and odor masking

- Lower risk of microbial growth

- Reduction in transport and storage costs

- Superior product stability and Shelf life

- High added value.

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2.2 Some species studied at LAPROFAR

Maytenus ilicifolia Passiflora alata Bauhinia forficata Rosmarinus officinalis Lippia sidoides Bidens pilosa

Cybopogun citratus Petiveria aliacea Dalbergia ecastaphyllum Cissus verticillata Camellia sinensis Psidium guajava

Hymenaea courbaril Sygizium aromaticum Arrabidaea chica Ananas comosus Eugenia pyriformis

2.3

Pro

du

cti

on

pro

ce

ss

Harvesting and pre-

processing of Herbal

Material

Extraction

/Filtration/Concentration of

Bioactives Substances

Carriers Addition

Spray drying

Parameters (Tgi,

Tgo, Wg, Ws/Wmax,

Cs, Atomization)

Freeze drying

Parameters (vacuum

pressure, heating

plate temperature)

Fluid bed drying

Parameters (Tgi, Tgo,

Wg, Ws/Wmax, Cs, bed

of inerts, atomization)

Drying

Powder properties

Xp, thermal degradation, solubility,

pH, bulk and tapped density, size and

particles morphology, thermal

behavior, color, chemical

composition, stability testing

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2.4 Carriers

Drying process

Aerosil®

Colloidal silicon

dioxide

Aerosil®:Cellulose MC 102

(25:75)

- Maltodextrin

- Arabic gum

- Starch

Spray drying Spouted bed

drying

http://www.andaluciainvestiga.com/sgcArchivos/FQM/grandes/ci

clodextrina.jpg www.worldsbestoil.ca/Amsoil-Image-

β-cyclodextrin

http://www.nauticurso.com.br/loja/product_info.php?products_i

d=523

Aerosil®

Cellulose

Freeze drying

2.5 Experimental results

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2.5.1 Technological products from Bidens pilosa

-Cortés Rojas, D.F. Standardized dried extracts of Bidens pilosa L.:

Technological development and evaluation of biological activity.

2011. 165 f. MSc. Dissertation. FCFRP/USP, Ribeirão Preto, 2011

(Patent pending).

* Biological activity

- Liver protector and jaundice treatment

- Antioxidant

- Antimalaric

- Antimicrobial

- Antiinflammatory

Drying

composition Carrier 1

Proportion

carrier 1

(%)

Carrier 2

Proportion

carrier 2

(%)

F1 Aerosil 200® 100 - -

F2 β-cyclodextrin 100 - -

F3 Aerosil 200® 25 Celullose MC-102 75

F4 Aerosil 200® 25 Maltodextrin DE 10 75

- B. pilosa compositions feed to Spray- and Spouted bed dryers

* Dry basis

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Spray dryer Spouted Bed dryer

Dryers used

Tgi = 150 C, Ws/Wmax =15 % Q = 60 m3/h (SD) and Q = 72 m3/h (SBD)

H0 = 7.0 cm (SBD)

Visual aspect of the product

Aerosil 200® β-cyclodextrin Aerosil 200®:Cellulose Aerosil 200®:Maltodex

SB

SD

* chemical composition (HPLC), Xp, thermal degradation, solubility, size, particles

morphology, X-ray diffraction, bulk and tapped density, thermal behavior, color, stability

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Chromatographic finger-print of the dried product

C H 3

O H

H

H O

R açucar

1 2 3 5

Rutin Hyperoside

4,5 Dicaffeoylquinic acid polyacetylene

www.bktechnology.com

Colum: C18, Mobile fase: gradient acetonitrile:acidifided water, ʎ: 254nm

Markers degradation

F1 F2 F3 F4

Spray drying

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Markers degradation

F1 F2 F3 F4

Spouted bed drying

- Water solubility of the SD- and SBD product.

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Scanning Electron Microscopy (SEM) SB

SD

1000X

a d c b

e f g h

Aerosil 200® β-cyclodextrin Aerosil 200®:Cellulose Aerosil 200®:Maltodex

- X-ray diffraction

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Title: Microparticle containing volatile compounds, production process and

pharmaceutical compositions (Brazilian Patent PI0704902-1A2)

2.5.2 Technological products from Lippia sidoides

Lippia sidoides

Essential

Oil

Encapsulated Extract

Essential Oil Loaded Microparticles

Herbal Extract

Spray drying

Preparation of

Encapsulating Compositions

(Addition of Carriers)

2.6 Challenges of herbal medicinal products

- Solubility problems (water or in lipidic systems), making tricky

their direct use in many pharmaceutical, cosmetic or food systems

-Lipid solubility and molecular size of many natural compounds

significantly restrict its capability to transpose biological barriers,

causing poor systemic bioavailability

- Lack and difficulties to obtain information on the bioavailability

of herbal products in humans.

- Some compounds could be degraded in contact with digestive

fluids or with environment.

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3. Novel encapsulation technologies (Delivery systems for herbal products)

- polymeric nanoparticles and nanocapsules

- solid lipid nanoparticles

- cyclodextrin complexes

- liposomes

- phytosomes

- emulsion based systems

- co-crystallization

- dendrimers encapsulation ?

Fang, Z. and Bhandari, B. Trends in Food Science & Technology 21 (2010) 510-523

3.1 Encapsulation technologies to deliver natural compounds

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Encapsulation technologies to deliver natural compounds

* High energy methods

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* Ultrasound processing

Buchi’s nano spray dryer

Spray freezing dryer

Spray drying/cooling

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Fluid and spouted bed dryers

a) bed with atomizer above; b) Wurster-type bed; c) rotary fluid bed

d) bidimensional spouted bed.

(Source: http://www.glatt.com)

* Suspended state process (fluid beds)

( a ) ( b ) ( c ) ( d )

3.3 Product characterization

- size

- dissolution tests

- solubility

- permeation

- absorption

- zeta potential

- X-ray diffraction

- thermal analysis

- Scanning and Transmission Electron Microscopy

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4. Closing remarks

Needs:

Technologies for the standardization, preservation and enhancement

of stability and bioavailability of natural bioactive compounds.

Strategies:

Delivery systems for natural products through

encapsulation technologies, improving their interaction with

biological barriers and perhaps providing target delivery.

Quality assurance:

Stability testing of product should also be pursued in order to

guarantee their quality, efficacy and safety during shelf life.

Prof. Dr. Wanderley Pereira Oliveira

Prof. Dra. Claudia Regina Fernandes Souza

M.Sc. Marcelo Luiz Lombardi Martinez

MSc. Maurette R. V. Fernandes

M.Sc. Tales Alexandre da Costa e Silva

M.Sc. Diego F. Cortés Rojas

M.Sc. Lucimara Benelli

M.Sc. Maira Neto Zampiér

Danielle Nishida Ramos

Camila Manoel Crnkovic

Financial support:

Research Group

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Laboratory of R&D on Pharmaceutical Processes

Researches on Drying and Agglomeration of

Pharmaceuticals and Bioproducts:

1. Development and standardization of dried phytochemical

preparations from medicinal and aromatic plants

2. Micro- and Nano-encapsulation of bioproducts through drying

3. Particle coating and agglomeration

4. Stability testing of herbal preparations

Thank You !!!

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3.2 Wall materials

*Synthetic HMW biodegradable polymers

- poly-a-cyanoacrylate alkyl esters

- polyvinyl alcohol

- polylactic alcohol

- polylacticcoglycolic acid

- polyethylene glycols

- Lipids

- waxes (carnauba and beeswax)

- natural fats and oils

- mono and di-glycerides

- phospholipids

- glycolipids

- Surfactants (GRAS status)

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- Natural polymers

- food proteins:

- albumin; gelatin; vegetable protein; casein;

b-lactoglobulin

- carbohydrates, hydrocolloids)

- Arabic gum; hydrolyzed starch; maltodextrins;

chitin; chitosan; alginates; guar gum; xhantam gum;

cellulose and cellulose derivates,..