Palonosetron hydrochloride dosage forms which have improved stability and bioavailability

摘要

Solid oral dosage forms of palonosetron hydrochloride, Methods to use the dosage forms to treat vomiting, and Methods for making the dosage forms. The dosage forms have improved stability and bioavailability, and are preferably in the form of liquid filled Capsules.Claim 1: A Soft Gel Capsule for oral administration comprising: a) an outer Coating of Soft Gel which has an oxygen permeability of less than about 1.0 x 10 (- 3 ml.cm cm2.24 - hour atmospheres); and (b) a lipophilic internal filling Liquid composition comprising: (i) greater than about 50% by weight of one or more lipophilic components; (ii) from about 1 to about 20% of water Weight homogenized in said one or more lipophilic components; (iii) near 0.05 mg. Close to 2.0 of palonosetron hydrochloride soluble as palonosetron or dispersed in the water; and (iv) from about 0.5 to about 8 percent by weight of a surfactant.Claim 1: a method to optimize the bioavailability and stability of palonosetron in a Gelatin capsule of palonosetron comprises: (a) to provide an external Coating of soft Gelatin that has an oxygen permeability of less than about 1.0 x 10 (- 3 ml.cm cm2.24 hour atmospheres); and (b) preparation of a composition for filling steps that comprise: (i) provide near 0.05 mg. About 2.0 as of palonosetron hydrochloride palonosetron where such cpd1 palonosetron consists in a quantity of less than 3.0% by weight; (ii) Dissolution or dispersion of palonosetron in water to form an aqueous mixture prepared in advance; (iii) Mix the aqueous mixture prepared with one or more lipophilic Ingredients, in a Weight ratio of the aqueous mixture prepared in advance to the Excipient It is less lipophilic 30: 70Lipophilic composition to form a miscible or homogeneous filler; (iv) mixing a Surfactant with this Water, this aqueous mixture prepared beforehand,The Composition of the filler; and (V) Balance of the amounts of Surfactant and water in the composition of the Filler For the bioavailability of the Gelatin capsule of palonosetron when ingested orally, and to decrease the degree of degradation of palonosetron (c); and filling the Outer Coating with the composition of the filler.