Ciclosporine is a cyclic peptide formed of 11 amino acids having a molecular weight of 1200.
Cyclosporine has a very low aqueous solubility but posses a fairly good solubility in vegetable oils and ethanol.
The traditional formulation was an emulsion preconcentrate delivered in a soft gelatin capsule. This formulation formed a coarse dispersion (emulsion) in the GIT after breakdown of the capsule in the stomach. Absorption of the drug occurred after solubilization of the oil droplets by the action of lipases, bile salts and lecithin. Using this formulation, a bioavailability that is obtained was 30%. However, it could vary from 10 - 60% in individual patients. This can be attributed to the drug is mainly absorbed from the mixed micelles formed in the GIT, but this process of micellisation is variable in patients depending on the bile salt concentration in the small intestine. This is frequent problem in liver transplant patients.
This formulation takes a great consideration from pharmaceutical scientists to improve the bioavailability with the aim to reduce the variability in patients. This was achieved by replacing emulsion preconcentrate with microemulsion preconcentrate. This new formula called (Neoral) leads to a rapid dispersion of the drug in the GIT after opening of the SGC to microemulsion droplets of less than 50 nm in diameter. Importantly, this dispersion is achieved independently of the action of lipases, bile salts and lecithin. In other words, its formulation by Self microemulsifying drug delivery systems (SMEDDS) is the used approach for this drug.
1) If the dose of cyclosporine is low (5-10 mg), then make sustained release delivery....sustained delivery minimize variation
2) If dose is high, govern the dissolution by formulation property but not due to bile salts..e.g. solid dispersion with Lutrol polymers
3) Change absorption window
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