Hydrogels, although seldom used in the ocular therapeutic practice, may offer various advantages over solutions and ointments. The present report describes the application of two distinct approaches, mucoadhesion and reduced drug solubility, to the development of improved hydrogels for delivery of pilocarpine. Five different polymeric materials, of natural, semi-synthetic and synthetic origin (xyloglucan gum, xanthan gum, pectin, hydroxypropylmethylcellulose and polyvinyl alcohol) were used at different concentrations to prepare two series of iso-viscous hydrogels (Series 1 and 2), each of which was characterized by a different apparent (pseudoplastic) viscosity (η' = 0.03 and 6.00 Pa·s at a shear rate, γ = 1.0 s-1). The more viscous gels (Series 2), tested in vitro for adhesion on hog gastric mucin (HGM), showed high work of adhesion (W) values. Series 1 and 2 hydrogels contained pilocarpine as the nitrate (PiNO3, 2.0% w/w), while a third hydrogel series (Series 3), having the same polymer composition and viscosity as Series 2, contained pilocarpine as a poorly soluble tannic acid complex (Pi/TA). All hydrogels were tested in vivo on rabbits for pilocarpine release to the tear fluid and for miotic effect. In two cases the transcorneal delivery of the drug was also evaluated. The overall biological activity increased in the order Series 1 < Series 2 < Series 3. The present preliminary results appear to indicate that the use of a sparingly soluble pilocarpine complex (Pi/TA) in combination with selected viscous, mucoadhesive hydrogels can result in prolonged activity and in increased bioavailability.
Hydrogels for ocular delivery of pilocarpine: Preliminary evaluation in rabbits of the influence of viscosity and of drug solubility
BURGALASSI, SUSI;CHETONI, PATRIZIA;SAETTONE, MARCO FABRIZIO
1996-01-01
Abstract
Hydrogels, although seldom used in the ocular therapeutic practice, may offer various advantages over solutions and ointments. The present report describes the application of two distinct approaches, mucoadhesion and reduced drug solubility, to the development of improved hydrogels for delivery of pilocarpine. Five different polymeric materials, of natural, semi-synthetic and synthetic origin (xyloglucan gum, xanthan gum, pectin, hydroxypropylmethylcellulose and polyvinyl alcohol) were used at different concentrations to prepare two series of iso-viscous hydrogels (Series 1 and 2), each of which was characterized by a different apparent (pseudoplastic) viscosity (η' = 0.03 and 6.00 Pa·s at a shear rate, γ = 1.0 s-1). The more viscous gels (Series 2), tested in vitro for adhesion on hog gastric mucin (HGM), showed high work of adhesion (W) values. Series 1 and 2 hydrogels contained pilocarpine as the nitrate (PiNO3, 2.0% w/w), while a third hydrogel series (Series 3), having the same polymer composition and viscosity as Series 2, contained pilocarpine as a poorly soluble tannic acid complex (Pi/TA). All hydrogels were tested in vivo on rabbits for pilocarpine release to the tear fluid and for miotic effect. In two cases the transcorneal delivery of the drug was also evaluated. The overall biological activity increased in the order Series 1 < Series 2 < Series 3. The present preliminary results appear to indicate that the use of a sparingly soluble pilocarpine complex (Pi/TA) in combination with selected viscous, mucoadhesive hydrogels can result in prolonged activity and in increased bioavailability.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
