ABSTRACT
The present study was intended to develop a controlled released osmotic pump capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in different oils, the pseudo-ternary phase diagram experiments and the different drug loading experiments were conducted in the preliminary screening studies. Controlled release of NM required an osmotic pump capsule comprising a coated semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release follows zero-order kinetics after oral administration. Polyethylene glycol content, used as a pore-forming agent, coating mass, and drug release orifice size were key factors affecting drug release behavior according to the single methods and were optimized through response surface methodology. The NM-loaded SMEDDS droplet size and the 1H NMR mass spectrogram of the novel capsule were determined. The droplet size of the reconstituted microemulsion was 39.9 nm and 1H NMR analysis showed NM dissolution in the microemulsion. The dissolution test performed on three batches of NM-SMEDDS capsules-prepared using optimal preparation methods-indicated the capsule to deliver a qualified drug delivery with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs were successfully developed and displayed a qualified release rate in vitro.
Subject(s)
Drug Delivery Systems/methods , Drug Liberation , Nimodipine/chemical synthesis , Administration, Oral , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/pharmacokinetics , Capsules , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Drug Delivery Systems/instrumentation , Drug Liberation/physiology , Emulsions/administration & dosage , Emulsions/chemistry , Emulsions/pharmacokinetics , Infusion Pumps, Implantable/trends , Nimodipine/administration & dosage , Nimodipine/pharmacokinetics , Osmosis/physiology , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/pharmacokinetics , SolubilityABSTRACT
Nimodipine, an antagonist of the L-type calcium ion channel, was labelled with 11C for in vivo positron emission tomography studies of dihydropyridine binding in the human brain. The synthesis was based on esterification of the corresponding acid (W2100) using [2-11C]isopropyl iodide as the labelling precursor. The effects of different bases, solvent mixtures and reaction temperatures on radiochemical yields were investigated. The synthesis including purification by semi-preparative reversed-phase HPLC, required 60-65 min. Conversion of [2-11C]isopropyl iodide to [isopropyl-11C] nimodipine was of the order of 60-80%. The radiochemical yield (isolated) was 20-25%, based on [11C]carbon dioxide. The specific activity of the isolated product varied from 4-40 GBq/mumol (end-of-synthesis).
