drying and encapsulation of active phytopharmaceutical ingredients
DESCRIPTION
Laboratory of Research and Development of Pharmaceutical ProcessesTRANSCRIPT
12/7/2012
1
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
12/7/2012
2
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).
12/7/2012
3
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.
12/7/2012
4
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
12/7/2012
5
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
12/7/2012
6
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
12/7/2012
7
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
12/7/2012
8
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
12/7/2012
9
Markers degradation
F1 F2 F3 F4
Spouted bed drying
- Water solubility of the SD- and SBD product.
12/7/2012
10
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
12/7/2012
11
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.
12/7/2012
12
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
12/7/2012
13
Encapsulation technologies to deliver natural compounds
* High energy methods
12/7/2012
14
* Ultrasound processing
Buchi’s nano spray dryer
Spray freezing dryer
Spray drying/cooling
12/7/2012
15
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
12/7/2012
16
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
12/7/2012
17
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 !!!
12/7/2012
18
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)
12/7/2012
19
- 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,..