Cyclosporine soft gelatin capsules

Similar labeling language also in the labeling of NEORAL SOFT GELATIN CAPSULES and SOLUTION (Novartis) (cyclosporine) MODIFIED March 2004. 

Erratic absorption of soft gelatin capsules and oral solution necessitates 2 Si. repeated monitoring of cyclosporine blood levels... 

Sirolimus solution - For simultaneous administration, the mean i i and AUC of sirolimus were increased by 116% and 230%, respectively, relative to administration of sirolimus alone. However, when given 4 hours after Neoral Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]) administration, sirolimus msx AUC were increased by 37% and 80%, respectively, comparedto sirohmiis alone. Cyclosporine clearance was reduced only after multiple-dose administration over 6 months. 

Cyclosporine A absorption was evaluated following oral administration of the regular Sandimmun soft gelatin capsule and the Neoral microemulsion formulation to patients with psoriasis. The Neoral formulation showed 32% increased mean AUC value, increased Cmax, decreased tmax and reduced variability between patients (Figure 6.4) [42],... 

FIGURE 6.4 Individual plasma cyclosporine A profiles following oral administration of Neoral microemulsion formulation (a) and the regular Sandimmun soft gelatin capsule (b) in psoriasis patients. (From Erkko, P., et al., Br. J. Dermatol., 136, 82, 1997. With permission.)... 

The first commercial formulation of cyclosporin (Sandimmun) contained drug, LCT, ethanol, and polyglycolized LCT administered as either an oral solution/dispersion in water or milk or filled into a soft gelatin capsule. The soft-gel formulation produced a crude oil in water emulsion on capsule rupture in situ. The biopharmaceutical performance of the Sandimmun formulation, however, was relatively poor, because absorption was variable, incomplete (=30%), and affected by food [63-67],... 

Sorbitan monooleate, polysorbate 80, and unsaturated polyglycolyzed glycerides (Labrafils) are components in the cyclosporin formulations Gengraf and Sandimmune. Bexarotene is a benzoic acid derivative, which is a selective activator of the retinoid X receptor indicated for the treatment of T-cell lymphoma, and is solubilized in a mixture of Polysorbate 20 and PEG 400 (in combination with povidone and BHA as an antioxidant) in 75 mg Targretin soft gelatin capsules. 

The highest level of complexity of lipid-based formulations in currently marketed products can be illustrated by three cyclosporin A products, which contain mixtures of five or six excipients and are microemulsion preconcentrates. Gengraf , Neoral , and Sandimmune soft gelatin capsules are all stored at room temperature. 

Cyclosporin A in soft gelatin capsules in a generic by Sidmak. 

There are a few marketed drug delivery systems containing microemulsions that are related to the lipid systems we describe here. Sandimmune Neoral (Novartis, Switzerland) [17], which delivers the lipophilic peptide cyclosporin A, is based on medium-chain triglycerides obtained from coconut oil, a semisynthetic emulsifier (ricinoleate), and propylene glycol. The absorption of the drug taken orally as a microemulsion increases dramatically compared to that of an aqueous suspension [17]. Another marketed example, in which Cs/Cio triglycerides from coconut oil are used, is a soft gelatin capsule of vitamin D3 [18]. 

SEDDS are particularly applicable for orally administered drugs, in soft or hard gelatin capsules that disintegrate in the gastrointestinal fluids (Sandri et al., 2010). Drugs with dissolution and bioavailability issues as fenofibrate (Soares et al., 2013), celecoxib (Fonte et al., 2011), or cyclosporine (Jin et al., 2011) have been formulated into SEDDS with success improvement of the oral controlled release of those drugs. 

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