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  • Cyclodextrin-crosslinked poly(acrylic acid): adhesion and controlled release of diflunisal and fluconazole from solid dosage forms.

Cyclodextrin-crosslinked poly(acrylic acid): adhesion and controlled release of diflunisal and fluconazole from solid dosage forms.

AAPS PharmSciTech (2013-01-12)
Marguerite J Kutyła, Michael W Boehm, Jason R Stokes, P Nicholas Shaw, Nigel M Davies, Ross P McGeary, Jonathan Tuke, Benjamin P Ross
ABSTRACT

The controlled release of diflunisal and fluconazole from tablets made of novel polymers, poly(acrylic acid) (PAA) crosslinked with either β-cyclodextrin (βCD) or hydroxypropyl-βCD (HPβCD), was investigated and Carbopol 934P (Carbopol) was used as a highly crosslinked PAA for comparison. Diflunisal strongly associates with βCD-PAA and HPβCD-PAA polymers (Ka of 486 and 6,055 M(-1) respectively); thus, it was physically mixed into the conjugates and also precomplexed to identify whether decomplexation has any influence on release kinetics. Fluconazole has poor complexing ability (Ka of 34 M(-1) with HPβCD-PAA); thus, it was only tested as a physical mixture. Swelling and adhesion studies were conducted on all tablet combinations and adhesivity of the CD-PAA polymer tablets was maintained. Diflunisal release was much slower from HPβCD-PAA tablets than from βCD-PAA, suggesting that a higher degree of complexation retards release. The precomplexed diflunisal release was also slower than the physically mixed diflunisal of the corresponding conjugate. The release closely followed zero-order kinetics for HPβCD-PAA, but was more sigmoidal for βCD-PAA and especially Carbopol. Conversely, poorly associating fluconazole released in almost exactly the same way across both polymers and Carbopol, indicating that the release kinetics of poorly associating drugs are not influenced by the presence of cyclodextrins. In view of the varying profiles and release rates shown with diflunisal for the different polymers, the fluconazole data support the concept that adequate complexation can indeed modulate the release kinetics of drugs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Poly(acrylic acid, sodium salt) solution, average Mw ~8,000, 45 wt. % in H2O
Sigma-Aldrich
Poly(acrylic acid) solution, average Mw ~250,000, 35 wt. % in H2O
Sigma-Aldrich
Poly(acrylic acid, sodium salt) solution, average Mw ~1,200, 45 wt. % in H2O
Sigma-Aldrich
Poly(acrylic acid) solution, average Mw ~2,000, 50 wt. % in H2O, electronic grade
Sigma-Aldrich
Poly(acrylic acid) solution, average Mw ~100,000, 35 wt. % in H2O
Supelco
Diflunisal, analytical standard
Supelco
Poly(acrylic acid sodium salt), analytical standard, for GPC, 16,000
Sigma-Aldrich
Poly(acrylic acid), average Mv ~4,000,000
Sigma-Aldrich
Poly(acrylic acid sodium salt), average Mw ~2,100
Sigma-Aldrich
Poly(acrylic acid sodium salt), average Mw ~5,100 by GPC, powder
Supelco
Poly(acrylic acid), analytical standard, average Mn 130,000 (Typical)
Sigma-Aldrich
Poly(acrylic acid), average Mv ~450,000
Sigma-Aldrich
Poly(acrylic acid)
Sigma-Aldrich
Poly(acrylic acid), average Mv ~1,250,000
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Poly(acrylic acid), average Mv ~3,000,000