Drying and Encapsulation of Active Phytopharmaceutical Ingredients

12/7/2012

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

Cybopogun citratus Petiveria aliacea Dalbergia ecastaphyllum

2.3 Production process

Hymenaea courbaril

Sygizium aromaticum

Rosmarinus officinalis Lippia sidoides

Bidens pilosa

Cissus verticillata

Camellia sinensis

Psidium guajava

Arrabidaea chica

Ananas comosus

Eugenia pyriformis

Harvesting and preprocessing of Herbal Material

Extraction /Filtration/Concentration of Bioactives Substances

Carriers Addition

Drying

Spray drying Parameters (Tgi, Tgo, W g, W s/W max, Cs, Atomization)

Freeze drying Parameters (vacuum pressure, heating plate temperature)

Fluid bed drying Parameters (Tgi, Tgo, W g, W s/Wmax, Cs, bed of inerts, atomization)

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 Aerosil®:Cellulose MC 102 (25:75)

β-cyclodextrin

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

www.worldsbestoil.ca/Amsoil-Image-

Aerosil® Colloidal silicon Aerosil® dioxide

http://www.nauticurso.com.br/loja/product_info.php?products_i d=523

Spray drying

Cellulose

Drying process

Spouted bed drying

- Maltodextrin - Arabic gum - Starch

Freeze drying

2.5 Experimental results

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2.5.1 Technological products from Bidens pilosa * Biological activity - Liver protector and jaundice treatment - Antioxidant - Antimalaric - Antimicrobial - Antiinflammatory -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).

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

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

* Dry basis

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Dryers used

Spray dryer

Spouted Bed dryer

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 β-cyclodextrin

Aerosil 200®:Cellulose Aerosil 200®:Maltodex

SD

SB

Aerosil 200®

* 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

Rutin

Hyperoside

4,5 Dicaffeoylquinic acid

polyacetylene

H H3 C OH H

O R

açucar

www.bktechnology.com

1

2

3

5

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

Markers degradation Spray drying F1

F2

F3

F4

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Markers degradation Spouted bed drying F1

F2

F3

F4

- Water solubility of the SD- and SBD product.

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Scanning Electron Microscopy (SEM) Aerosil 200®

Aerosil 200®:Cellulose Aerosil 200®:Maltodex

b

c

d

f

g

h

SB

a

β-cyclodextrin

SD

e

1000X

- X-ray diffraction

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2.5.2 Technological products from Lippia sidoides

Encapsulated Extract Herbal Extract

Preparation of Encapsulating Compositions (Addition of Carriers)

Lippia sidoides

Essential Oil

Spray drying

Essential Oil Loaded Microparticles

Title: Microparticle containing volatile compounds, production process and pharmaceutical compositions (Brazilian Patent PI0704902-1A2)

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 ?

3.1 Encapsulation technologies to deliver natural compounds

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

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Encapsulation technologies to deliver natural compounds

* High energy methods

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* Ultrasound processing

Spray drying/cooling

Buchi’s nano spray dryer

Spray freezing dryer

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* Suspended state process (fluid beds)

(a)

(b)

(c)

(d)

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)

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.

Research Group 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:

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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

ThankYou !!!

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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,..

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