Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hydrophilic solvents onto high surface area carriers.
The dissolution rate of the model drugs carbamazepine and nifedipine was improved by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile solvents onto carriers with a large surface area. This was accomplished by dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2-pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil) or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil 200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil because of the smaller surface area. Differential scanning calorimetry measurements showed higher interactions between drugs and Kollidon compared to Aerosil, suggesting a low aggregation of precipitated drug particles. The drug release from the adsorbent systems was enhanced when compared to micronized drug and independent of the drug loading in the investigated range. The drugs were also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40-hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto Kollidon. These adsorbent systems also exhibited an increased dissolution rate when compared to pure drug.
Friedrich
Heike
H
College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Fussnegger
Bernd
B
Kolter
Karl
K
Bodmeier
Roland
R
D000327:Adsorption; D000927:Anticonvulsants / Q000737:chemistry*; D002121:Calcium Channel Blockers / Q000737:chemistry*; D002220:Carbamazepine / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D004337:Drug Carriers; D005079:Excipients; D011760:Pyrrolidinones; D012997:Solvents; D020442:Poloxamer; D002220:Carbamazepine; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D011205:Povidone; D009543:Nifedipine; C028537:2-pyrrolidone; D000432:Methanol