Preparation and Characterization of Piroxicam

Microcrystals, for Better Dissolution Profile

Mohammed Dahmash

Main Points

• Discuss the dissolution problem of piroxicam and

how to solve it.

• Elaborate on how the 0.3% of Kolliphor® EL

surfactant produce micronized crystals.

Introduction

• The poor dissolution of hydrophobic drugs results in:

High drug precipitation, low drug absorption,

low drug bioavailability, GI injury and high cost(1).

1. Harvey, R A, Clark M A & Finkel R. Chapter 41: Anti-inflammatory Drugs. Lippincott's Illustrated Reviews:

Pharmacology. New York : Lippincott Williams & Wilkins, 2009, p. 508.

Aim and Objectives

Enhance the dissolution of piroxicam by using in-situ

crystallization method with the aid of Kolliphor® EL.

Then, analyse the obtained crystals by various

techniques to investigate the micronization effects.

Materials and Methods

• Kolliphor® EL,

• In situ crystallization(2),

• Lyophilisation,

• Paddle-apparatus dissolution,

• Polarized microscopy,

• Zeta size analyser (ZSA), and

• Fourier-transform infrared spectroscopy (FTIR).

2. Rasenack, N, Steckel, H & Müller, B. Preparation of microcrystals by in situ micronization. Journal of

Powder Technology, Vols. 143-144, 2004, pp. 291-296.

Results and Discussion

• A significant increase in dissolution with both 0.1 and

0.3% of Kolliphor® EL (p-values≤0.05) and

significant decrease in the effective diameter with

0.3% of Kolliphor® EL (p=0.0375), result in:

Decreased particle size and surface tension, increased

surface area and wettability(3).

3. Elkordy A A, Jatto A & Essa E. In situ controlled crystallization as a tool to improve the dissolution of

Glibenclamide. International Journal of Pharmaceutics, Vol. 428, 2012, pp. 118-120.

The dissolution profile of piroxicam in different

formulations

0.3 % of

Kolliphor® EL

0.1% of

Kolliphor® ELControlRaw

drug

Piroxicam microcrystals of 0.3% Kolliphor® ELPiroxicam crystals of 0.1% Kolliphor® EL

Raw piroxicam Piroxicam crystals without Kolliphor® EL

Results and Discussion (Continued)

• Enhanced “in process” stability with 0.1 and 0.3% of

Kolliphor® EL, mainly because the amide stretch of

piroxicam was conserved (4)

Piroxicam structure, highlighting its amide group

4. Watson, D G. Infrared Spectroscopy. Pharmaceutical Analysis: A Textbook for Pharmacy Students and

Pharmaceutical Chemists. Philadelphia, USA: Elsevier Churchill Livingstone, 2005, pp. 113-125.

5001000150020002500300035000.55

0.6

0.65

0.7

0.75

0.8

0.85

0.9

0.95

1

Tra

nsm

itta

nce

Wavenumbers [cm-1]

Amide stretch of piroxicam at 3336 cm-1

Raw piroxicam

5001000150020002500300035000.625

0.7

0.8

0.9

11.025

Wavenumbers [cm-1]

Primary amine that resulted

from amide hydrolysis

Tra

nsm

itta

nce

Piroxicam crystals without

Kolliphor® ELEL

5001000150020002500300035000.4

0.5

0.6

0.7

0.8

0.9

1

1.1

Wavenumbers [cm-1]

Amide stretch of piroxicam

was conserved

Tra

nsm

itta

nce

Piroxicam crystals with

0.1 and 0.3% of Kolliphor® EL

Conclusion

• The microcrystallized formulation can be obtained with 0.3% of Kolliphor® EL and used to enhance piroxicam dissolution, to result in:

less GI side effects and high cost-effectiveness.

• Future work...

The Tunable Resistive Pulse Sensing (TRPS) device would be recommended to be used for:

obtaining more accurate information based on particle by particle sizing of piroxicam micro/nano-crystals.

Acknowledgements

• I thank with gratitude and sincerity:

Miss Zahra Batool,

Mrs Muna Al-lami,

Dr Amal Elkordy, and

Dr Cheng Chaw.

Thank you

Any questions ?