INFLUENCE OF PARTICLE SIZE REDUCTION ON THE DIFFUSION OF PIROXICAM AQUEOUS GEL DOSAGE FORM
Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) and classified as Biopharmaceutical Classification System (BCS) class II. It has a high permeability but low solubility character. This leads to low water solubility and consequently low diffusion from aqueous gel base. In order to increase the diffusion of Piroxicam from aqueous gel dosage form, the particle size of Piroxicam is reduced. Micro-suspended Piroxicam was generated using high pressure homogenizer with 3 different pressures at 50, 100 and 150 bar each 10 cycles. The particle size of micro-suspension was measured using the particle size analyzer and showed an averaae of 1 micrometer. Dissolution of micro-suspension Piroxicam and raw material Piroxicam suspension was performed using paddle type apparatus with water as medium. Physical observation of micro-suspension Piroxicam using light microscope and analysis using Powdered X-ray Diffraction was performed. The percentage of dissolution of micro-suspension Piroxicam was at 30% which is significantly higher compared to raw material that was only 11% within 120 minutes. The microscopic image of micro-suspension Piroxicam was observed to be tiny compared to raw material. There are no polymorphic changes in the crystal of Piroxicam after being treated with high pressure homogenizer. The micronized aqueous gel contains of micronized Piroxicam, hydroxypropylmetylcellulose (HPMC), sodium carboxymethylcellulose (Na-CMC), benzyl alcohol, triethanolamine (TEA) and distilled water. Organoleptic together with pH and viscosity test was performed on the aqueous gel as physical stability test for 2 months. Content uniformity test was performed by centrifuging Piroxicam gel mixture with methanol and tested the supernatant using UV-VIS spectrophotometer. Diffusion test was conducted using Franz static diffusion cell with shed snake skin of Phyton reticulates as the membrane. Release amount of diffused Piroxicam was determined using UV-VIS spectrophotometer. Both the micro-suspended Piroxicam gel and raw material Piroxicam gel showed the content of Piroxicam in the gel was within the acceptable range of 95.0%-105.0%. The diffusion of Piroxicam, from micro-suspended aqueous gel is also significantly higher which was over 300µg/cm- than release from raw material Piroxicam aqueous gel which was about 200ug/cm2 in 24 hours. However, no significant different in the release of Piroxicam from micro-suspended Piroxicam aqueous gel compared with marketed gel. The physical stability of micro-suspended Piroxicam aqueous gel showed no sign of degradation just as the raw material piroxicam aqueous gel. Thus, particle size reduction does have influence on the diffusion of Piroxicam aqueous gel without any deterioration.