Enhanced bioavailability of piroxicam using Gelucire 44/14 and Labrasol: in vitro and in vivo evaluation

YÜKSEL N., Karatas A., Ozkan Y., Savaser A., Ozkan S. A., Baykara T.

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, cilt.56, sa.3, ss.453-459, 2003 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 56 Sayı: 3
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1016/s0939-6411(03)00142-5
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.453-459
  • Anahtar Kelimeler: piroxicam, Gelucire 44/14, Labrasol, semi-solid dispersion, dissolution, human, bioavailability, pharmacokinetics, SOLID DISPERSIONS, DISSOLUTION, ABSORPTION, FORMULATIONS, PLASMA, FORM
  • Ankara Üniversitesi Adresli: Evet

Özet

Piroxicam is a non-steroidal anti-inflammatory drug that is characterized by low solubility and high permeability. The purpose of the study was to investigate the in vitro and in vivo performance of the semi-solid dispersion prepared with Gelucire 44/14 and Labrasol into hard gelatin capsules (GL) for enhancing the dissolution rate of the drug. The results were evaluated by comparing with pure piroxicam filled into hard gelatin capsules (PP) and a commercially available tablet dosage form containing a piroxicam:p-cyclodextrin complex (CID). The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). Amongst the dosage forms, GL provided at least 85% piroxicam dissolution within 30 min in each of the media, behaving like a fast-dissolving immediate release drug product. Oral bioavailability of 20 mg piroxicam in GL, CD, and PP was compared after administration of a single dose to eight healthy volunteers. Three treatments were administered in crossover fashion, separated by a washout period of 2 weeks. Piroxicam was monitored in plasma by high-performance liquid chromatography. The apparent rate of absorption of piroxicam from GL (C-max = 2.64 mug/ml, t(max) = 82.5 min) wa significantly higher than that of the PP (C-max = 0.999 mug/ml, t(max) = 144 min) (P < 0.05) and similar to that of CD (C-max = 2.44 mug/ml, t(max) = 120 min) (P > 0.05). The relative bioavailability values as the ratios of mean total AUC for GL relative to PP and CD, were 221 and 98.6%. Piroxicam is characterized by a slow and gradual absorption via the oral route and this causes a delayed onset of therapeutic effect. Thus, plain piroxicam preparations are not indicated for analgesia. The results of the in vivo study revealed that the GIL dosage form would be advantageous with regards to rapid onset of action, especially in various painful conditions where an acute analgesic effect is desired. (C) 2003 Elsevier B.V. All rights reserved.