Dissolution, bioavailability and ulcerogenic studies on piroxicam-nicotinamide solid dispersion formulations.

Abstract

Solid dispersions with different ratios of Piroxicam and Nicotinamide (as a carrier) were prepared by fusion method. Drug-carrier interactions in the solid state were ascertained using phase-diagram, X-ray diffraction (XRD) and Differential scanning colorimetry (DSC). Select ratios of the formed piroxicam-nicotinamide solid dispersions and their corresponding physical mixtures were formulated into tablets and capsules. The dissolution characteristics of the formed solid dispersions, physical mixtures and their formulations were compared with pure piroxicam in 900 ml of 0.1 N HCl (pH 1.2) at 37 +/- 0.5 degrees C, 50 rpm using USP XXI paddle apparatus. Solid dispersion capsule PNC1 (containing 1:5--drug-carrier ratio solid dispersion) and the corresponding physical mixture capsule PNC1A were used for bioavailability studies in healthy human volunteers. Further, ulcer indices of the prepared solid dispersion and their corresponding physical mixture were compared with pure piroxicam in rats. The DSC, XRD and phase diagram indicated the formation of solid dispersed system. The prepared dispersion showed better dissolution than the corresponding physical mixture and pure drug. The fabricated formulation complied with the pharmacopoeial limits for physico-chemical properties and the solid dispersion capsules PNC1 and PNC2 (containing 1:9 ratio of drug to carrier solid dispersion) showed 3 and 6.6 fold increase and 3.2 and 8 fold increases in dissolution rate compared to the corresponding physical mixture capsules (PNC1A and PNC2A), respectively. The solid dispersion capsule PNC1 showed significantly higher absorption and dissolution and consequently better bioavailability than the corresponding physical mixture capsule (PNC1A) in healthy human volunteers. The ulcer indices of the prepared dispersions were significantly lower than the corresponding physical mixture and pure drug.

• Authors: M Mohan Verma, M Thilek Kumar, J Balasubramaniam, J K Pandit
• Journal: Bollettino chimico farmaceutico (Boll Chim Farm) Vol. 142 Issue 3 Pg. 119-24 (Apr 2003) ISSN: 0006-6648 [Print] Italy
• PMID: 12806831 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Capsules
• Tablets
• Piroxicam
• Niacinamide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, chemistry, pharmacokinetics)
• Biological Availability
• Calorimetry, Differential Scanning
• Capsules
• Humans
• Niacinamide (adverse effects, chemistry, pharmacokinetics)
• Piroxicam (adverse effects, chemistry, pharmacokinetics)
• Rats
• Solubility
• Stomach Ulcer (chemically induced, pathology)
• Tablets
• X-Ray Diffraction