FuBio Seminar 27.8.2013

1. CELLULOSE BEADS IN DRUG DELIVERY
Dr Ruzica Kolakovic
Åbo Akademi University
Department of Biosciences
Pharmaceutical Science Laboratory

2. 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

3. Introduction
 Porous spherical cellulose particles with diameters in the micro- to
millimeterr scale.
Trygg et al., Chem. Rev.

4. Production
Yildir et al. submitted
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
Dissolving
Pulp
Dissolved
Cellulose
Pretreated
Pulp
Pretreatment in
Ethanol-Hydrochloric Acid
Mixing the pretreated pulp
with 7%NaOH and %12urea
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

5. 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)
Yildir et al. submitted
Good candidates as drug carriers

6. 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

7. 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

8. Drug loading efficacy
Drug Type of CBs
Dug
loading (%)
Theophylline
Non-
ionic
T1 3.7
T2 4.2
T3 5.0
Lidocain
hydrochloride
T1 23.2
T2 26.6
T3 27.3
Riboflavine sodium
posphate
T1 12.7
T2 13.0
T3 14.3
Piroxicam T2 10.8
Griseofulvin T2 22.1
Ranitidine
hydrochloride
Non-ionic 16.1
Anionic 20.1
Quinine sulphate
Non-ionic 3.3
Anionic 11.8
Drug loading (entrapment efficacy) is
dependent on concentration of drug
loading solution, drug choice and CBs
properties

9. Morphology studies
Quinine anionic
Ranitidin loaded non/ionic Ranitidin loaded anionic
Quinine non/ionic

10. Solid state characterization
(FTIR)
CMC
Ranitidine hydrochloride
Interactions
Possible interactions between
anionic groups of CBs
(originating from CMC) and
positively charged drugs

11. Drug release properties
0
10
20
30
40
50
60
70
80
90
100
0 200 400 600 800
Cumulativeamountofdrugreleased
(%)
Time (min)
Quinine sulfate pure substance
Non-ionic beads
Anionic beads
Drug release dependent on
type of CBs and choice of
drug

12. Processability of CBs
 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
Angle of repose of fast flo lactose ,
~ 35-40deg
 Tabletting
CBs successfully compressed
into tablets

13. Application of CBs in future
Uniformity of drug loading
Possibility of dose adjustment
Personalized dosing
Because no two patients are alike
Every bead carries the same amount of drug
Dose is adjusted by choosing the needed number of beads

14. 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)

15. 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

16. 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

17. THANK YOU FOR YOUR ATTENTION !