title: Ibuprofen-phospholipid solid dispersions: improved dissolution and gastric tolerance.
abstract: Solid dispersions of ibuprofen with various phospholipids were prepared, and the effect of phospholipids on the in vitro dissolution and in vivo gastrointestinal toxicity of ibuprofen was evaluated. Most phospholipids improved the dissolution of ibuprofen; dimyristoylphosphatidyl-glycerol (DMPG) had the greatest effect. At 45 min, the extent of dissolution of ibuprofen from the ibuprofen-DMPG system (weight ratio 9:1) increased about 69% compared to ibuprofen alone; the initial rate of dissolution increased sevenfold. Increasing the DMPG content from 9:1 to 4:1 in this system did not significantly increase the rate and the extent of dissolution. X-ray diffraction and scanning electron micrograph indicated a smaller crystallite size of ibuprofen with fairly uniform distribution in the ibuprofen-DMPG solid dispersion. A small amount of carrier phospholipid significantly increases the rate and the extent of dissolution, which may increase the bioavailability of ibuprofen. The number of ulcers >0.5mm in size formed in the gastric mucosa of rats following ibuprofen, DMPG, DMPC and DPPC solid dispersions (ibuprofen and phospholipid weight ratio 4:1) were 8.6 ± 6.2, 3.9 ± 5.3, 5.3 ± 4.9 and 9.1 ± 7.4, respectively. Solid dispersion of ibuprofen with DMPG was significantly less irritating to the gastric mucosa than ibuprofen itself (one-way ANOVA, p<0.05). Solid dispersion of ibuprofen and DMPG decreases the gastric side effects of ibuprofen.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, 1010 West Avenue B, Kingsville, TX, USA. hussain@pharmacy.tamhsc.edu
authors.forename: M Delwar
authors.initials: MD
authors.lastname: Hussain
authors.forename: Vipin
authors.initials: V
authors.lastname: Saxena
authors.forename: James F
authors.initials: JF
authors.lastname: Brausch
authors.forename: Rahmat M
authors.initials: RM
authors.lastname: Talukder
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D002725:Chloroform / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D019610:Cytoprotection; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D012997:Solvents; D000431:Ethanol; D002725:Chloroform; C002773:dimyristoylphosphatidylglycerol; C010942:1,2-distearoyllecithin; D004134:Dimyristoylphosphatidylcholine; D007052:Ibuprofen