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

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

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

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 (%)

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

Morphology studies Quinine anionic

Ranitidin loaded non/ionic Ranitidin loaded anionic

Quinine non/ionic

Solid state characterization (FTIR)

CMC

Ranitidine hydrochloride

Interactions

Possible interactions between

anionic groups of CBs

(originating from CMC) and

positively charged drugs

Drug release properties

0

10

20

30

40

50

60

70

80

90

100

0 200 400 600 800

Cu

mu

lati

ve a

mo

un

t o

f d

rug

rele

ase

d

(%)

Time (min)

Quinine sulfate pure substance

Non-ionic beads

Anionic beads

Drug release dependent on type of CBs and choice of drug

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

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

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 !