Guar-based monolithic matrix systems: effect of ionizable and non-ionizable substances and excipients on gel dynamics and release kinetics.
The effect of ionic and non-ionic excipients and additives as modulators of swelling and erosion kinetics and verapamil HCl release from guar-based matrix tablets was investigated. Tablet dissolution, erosion and water uptake studies were carried out using a modified USP 23 Apparatus 2 method. The kinetics of gel strength and texture development were studied by textural analysis. Near linear drug release over 24 h was obtained from formulations containing water soluble, ionizable sodium chloride and glycine. The contribution of Fickian release to overall drug release was lowest for these formulations and was correlated with greater gel strength and lower water uptake in the early time period. For soluble sugars (lactose and sucrose) the Fickian contribution to overall drug release was large and associated with pronounced curvilinear profiles. Water uptake was greatest for these additives (450% in 6 h). The lowest water uptake and negligible matrix erosion was observed for microcrystalline cellulose. Release from this formulation was predominantly Fickian. It was found that the physico-chemical nature of added excipients significantly influences the release kinetics from guar-based formulations. Ionic, water soluble materials (sodium chloride, glycine) reduce initial hydration of the matrix and thus have the ability to limit the initial rapid diffusion of drug and to sustain near linear release over 24 h.
Dürig
Thomas
T
School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Fassihi
Reza
R
D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics*; D005685:Galactans / Q000737:chemistry / Q000493:pharmacokinetics*; D005782:Gels / Q000737:chemistry / Q000493:pharmacokinetics*; D008351:Mannans / Q000737:chemistry / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D053149:Plant Gums; D012995:Solubility; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics; D014700:Verapamil / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D005079:Excipients; D005685:Galactans; D005782:Gels; D008351:Mannans; D053149:Plant Gums; D013607:Tablets; D014700:Verapamil; C007894:guar gum