Progesterone (P) is a natural hormone used as a drug to control reproductive function and for postmenopausal therapy. Oral and vaginal routes display low bioavailability and, in addition, oral route has a limited usefulness, because of P short half-life and extensive degradation after absorption. Therefore the injection route should be the preferred choice, since the oily solution and the aqueous suspension allow only intramuscolar administration. This encourages the research of new injectable pharmaceutical form with increase of the patient compliance. Water-soluble P formulations represent a suitable solution, because they could be administered also by subcutaneous route, therefore allowing auto medication and less pain during the treatment is expected. Pitha et al. described the use of Cyclodextrins to increase the water solubility of Progesterone (P), through the formation of an inclusion complex to obtain a water soluble formulation (1). Also other authors, using different physico-chemical methods (2, 3, 4), reported experimental evidences of the inclusion complex formation between P and b-cyclodextrin and derivatives. Among the cyclodextrins tested hydroxypropyl-b-cyclodextrin (HPBCD) is a suitable choice for formulations containing therapeutic concentration of P. The therapeutic dosage of P by injection varies from 5 to 200 mg. as a function of the specific pathology (5). HPBCD, displaying high water solubility (48% p/v), allows solubilisation of large quantity of P. Considering the formation of a 1:2 complex, it is possible to obtain solutions up to 50 mg/ml P, which is a considerable dosage in the progesterone therapy. In the development of P/HPBCD complex we observed the formation of a light precipitate under stability ICH conditions. Choi et al (4) and also by Pitha et al (1) noticed the precipitate formation, but its chemical structure was not elucidated. This work describes a method to obtain a P/HPBCD without insoluble particles, the physico-chemical characterization of the precipitate and of the purified inclusion complex.

New injectable formulation containing water soluble Progesterone-Hydroxypropyl-beta-cyclodextrin complex

FINI, ADAMO
2006

Abstract

Progesterone (P) is a natural hormone used as a drug to control reproductive function and for postmenopausal therapy. Oral and vaginal routes display low bioavailability and, in addition, oral route has a limited usefulness, because of P short half-life and extensive degradation after absorption. Therefore the injection route should be the preferred choice, since the oily solution and the aqueous suspension allow only intramuscolar administration. This encourages the research of new injectable pharmaceutical form with increase of the patient compliance. Water-soluble P formulations represent a suitable solution, because they could be administered also by subcutaneous route, therefore allowing auto medication and less pain during the treatment is expected. Pitha et al. described the use of Cyclodextrins to increase the water solubility of Progesterone (P), through the formation of an inclusion complex to obtain a water soluble formulation (1). Also other authors, using different physico-chemical methods (2, 3, 4), reported experimental evidences of the inclusion complex formation between P and b-cyclodextrin and derivatives. Among the cyclodextrins tested hydroxypropyl-b-cyclodextrin (HPBCD) is a suitable choice for formulations containing therapeutic concentration of P. The therapeutic dosage of P by injection varies from 5 to 200 mg. as a function of the specific pathology (5). HPBCD, displaying high water solubility (48% p/v), allows solubilisation of large quantity of P. Considering the formation of a 1:2 complex, it is possible to obtain solutions up to 50 mg/ml P, which is a considerable dosage in the progesterone therapy. In the development of P/HPBCD complex we observed the formation of a light precipitate under stability ICH conditions. Choi et al (4) and also by Pitha et al (1) noticed the precipitate formation, but its chemical structure was not elucidated. This work describes a method to obtain a P/HPBCD without insoluble particles, the physico-chemical characterization of the precipitate and of the purified inclusion complex.
5th World Meeting on Pharmaceutics Biopharmaceutics and Pharmaceutical Technology Geneva, Switzerland 27th -30th March 2006
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G. Zoppetti; N. Puppini; M. Pizzuti; A. Fini
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/31630
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