Comparison of the effect of chitosan and polyvinylpyrrolidone on dissolution properties and analgesic effect of naproxen.
The solubilizing and absorption enhancer properties towards naproxen of chitosan and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems prepared at various drug-polymer ratios by mixing, cogrinding or kneading, were characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on the drug-polymer ratio and the system preparation method. Chitosan was more effective than PVP, despite the greater amorphizing power of PVP as revealed by solid state analyses. The 3/7 (w/w) drug-carrier coground systems with chitosan and PVP were the best products enabling, respectively, an improvement of 4.8 and 3.6 times of drug dissolution efficiency. In vivo experiments in mice demonstrated that administration of 45 mg/kg of drug coground with PVP or chitosan resulted, respectively, in a 25 and 60% reduction of acetic acid-induced writhings in comparison to pure drug, which, instead, was statistically ineffective as compared to the control group. Moreover, the 3/7 (w/w) drug-chitosan coground product demonstrated an antiwrithing potency 2.4 times higher than the coground with PVP. Thus, the direct-compression properties and antiulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability towards the drug, make chitosan particularly suitable for developing a reduced-dose fast-release solid oral dosage form of naproxen.
Zerrouk
Naima
N
Laboratoire de Pharmacie Galénique, Faculté de Sciences Pharmaceutiques et Biologiques, Université de Paris V, Paris, France.
Mennini
Natascia
N
Maestrelli
Francesca
F
Chemtob
Chantal
C
Mura
Paola
P
D019342:Acetic Acid / Q000008:administration & dosage / Q000009:adverse effects; D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics*; D003460:Crystallization; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D008297:Male; D008722:Methods; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009288:Naproxen / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D011205:Povidone / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility / Q000187:drug effects*; D013678:Technology, Pharmaceutical
D000700:Analgesics; D009288:Naproxen; D048271:Chitosan; D011205:Povidone; D019342:Acetic Acid