CELLULOSE BEADS IN DRUG DELIVERY
Dr Ruzica Kolakovic
Åbo Akademi University
Department of Biosciences
Pharmaceutical Science Laboratory
Table of content
• Cellulose beads – production & properties
• Objectives of our work (Why CBs as drug carriers?)
• Our work with CBs so far
• Future plans/prospects
• Conclusions
Introduction
 Porous spherical cellulose particles with diameters in the micro- to
millimeterr scale.
Trygg et al., Chem. Rev
.
Production
Produced by coagulation of dissolved cellulose
Advantages of the production process
• Usage of environmental friendly solvents
• Possibility of tailoring in order to achieve beads of desirable properties
(size, porosity, charge, etc.)
• Possibility of scale up
Mixing the pretreated pulp
with 7%NaOH and %12urea
Dissolving
Pulp
Pretreated
Pulp
Pretreatment in
Ethanol-Hydrochloric Acid
Yildir et al. submitted
Dissolved
Cellulose
Cellulose
Beads
Precipitation of dissolved cellulose
in 0.5 M HNO3 solution at 25° C
in 2M HNO3 solution at 25° C
in 2M HNO3 solution at 50° C
Properties
Why CBs in drug delivery?
• Non - toxicity
• Biocompatibility
• High porosity → large specific surface
area
• High mechanical strength
• Relatively low cost
• Irreversible agglomeration upon drying
(hornification)
Good candidates as drug carriers
Yildir et al. submitted
Aim of our work
Investigate possible application of CBs as drug carriers
• Drug loading capacity (entrapment efficacy)
• Drug release properties
• Processability (flow properties, tabletting abilities )
• Behavior of nonionic vs. anionic CBs
Our work with CBs so far
 Drug loading (entrapment efficacy) studies have been performed with various
different compounds and several types of CBs (different charge, porosity, etc.)
Immersing method - simple two step method for drug loading
Drug loading efficacy
Drug
Type of CBs
Dug
loading (%)
T1
3.7
T2
4.2
T3
5.0
T1
23.2
T2
26.6
T3
27.3
T1
12.7
T2
13.0
T3
14.3
Piroxicam
T2
10.8
Griseofulvin
T2
22.1
Theophylline
Lidocain
hydrochloride
Nonionic
Riboflavine sodium
posphate
Ranitidine
hydrochloride
Quinine sulphate
Non-ionic
16.1
Anionic
20.1
Non-ionic
3.3
Anionic
11.8
Drug loading (entrapment efficacy) is
dependent on concentration of drug
loading solution, drug choice and CBs
properties
Morphology studies
Quinine non/ionic
Ranitidin loaded non/ionic
Quinine anionic
Ranitidin loaded anionic
Solid state characterization
(FTIR)
Ranitidine hydrochloride
CMC
Possible interactions between
anionic groups of CBs
(originating from CMC) and
positively charged drugs
Interactions
Drug release properties
Cumulative amount of drug released
(%)
100
90
Quinine sulfate pure substance
80
Non-ionic beads
70
Anionic beads
60
50
40
30
20
10
0
0
200
400
Time (min)
600
Drug release dependent on
type of CBs and choice of
drug
800
Processability of CBs
 Tabletting
 Flow properties - angle of repose test
Good flow properties (similar or better
than common direct compression fillers)
Angle of repose of CBs,
~ 24-30 deg
CBs successfully compressed
into tablets
Angle of repose of fast flo lactose ,
~ 35-40deg
Application of CBs in future
Personalized dosing
Because no two patients are alike
Uniformity of drug loading
Possibility of dose adjustment
Every bead carries the same amount of drug
Dose is adjusted by choosing the needed number of beads
Future work and ideas
 Oxidized CBs → contain larger portion of anionic groups (possibility
of reversible swelling and increase in loading capacity)
Hollow CBs → floating in aqueous medium
(possibility of gastro-retentive formulations)
Conclusions
CBs are promising drug carriers candidates
• Easy two step loading process
• Possibility of tailoring CBs properties and thus
release properties
• Easy processing into dosage forms (capsules,
tablets)
• Application in personalized dosing
Acknowledgements
M.Sc. Emrah Yildir
Hanne Redant
Laure De Boeck
Dr. Natalja Genina
Prof. Niklas Sandler
M. Sc. Jani Trygg
Prof. Pedro Fardim
FuBio Cellulose
THANK YOU FOR YOUR ATTENTION !