Cyclodextrin-containing poly(ethyleneoxide) tablets for the delivery of poorly soluble drugs: potential as buccal delivery system.
The aim of this work was to develop a tablet for the buccal delivery of the poorly soluble drug carvedilol (CAR), based on poly(ethyleneoxide) (PEO) as bioadhesive sustained-release platform and hydroxypropyl-beta-cyclodextrin (HPbetaCD) as modulator of drug release. As first, PEO tablets loaded with CAR/HPbetaCD binary systems with different dissolution properties were tested for CAR and HPbetaCD release features and compared to PEO tablets containing only CAR. When the drug was incorporated as CAR/HPbetaCD freeze-dried product, all CAR content was released from the tablet in about 10 h, displaying a constant release regimen after a transient. The effect of HPbetaCD incorporation on the release mechanism, was rationalized on the basis of the interplay of different physical phenomena: erosion and swelling of the tablet, drug dissolution, drug counter-diffusion and complex formation. In the second part of the study, the potential of HPbetaCD-containing PEO tablets as buccal delivery system for CAR was tested. It was found that the incorporation of HPbetaCD in the tablet did not alter significantly its good adhesion properties. The feasibility of buccal administration of CAR was assessed by permeation experiments on pig excised mucosa. The amount of CAR permeated from PEO tablet was higher in the case of HPbetaCD-containing tablets, the maximum value being obtained for CAR/HPbetaCD freeze-dried system. Our results demonstrate that, when the tablet is employed as transmucosal system, the role of drug dissolution enhancement in the hydrated tablet is much more relevant than in solution for increasing the delivery rate.
Cappello
Brunella
B
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
De Rosa
Giuseppe
G
Giannini
Lucia
L
La Rotonda
Maria Immacolata
MI
Mensitieri
Giuseppe
G
Miro
Agnese
A
Quaglia
Fabiana
F
Russo
Roberto
R
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000278:Administration, Buccal; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D008956:Models, Chemical; D009061:Mouth Mucosa / Q000378:metabolism; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry*; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013552:Swine; D013607:Tablets; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005079:Excipients; D011412:Propanolamines; D013607:Tablets; D047392:beta-Cyclodextrins; D000077261:Carvedilol; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols