Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP

Abstract

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

The application of povidone in the preparation of modified release tablets

“…The formulation consisting of 80% polyvinyl acetate (PVAc), 19% polyvinyl pyrrolidone (PVP), sodium lauryl sulfate and colloidal silicon dioxide in powder form is known as Kollidon SR. It has been shown to be a highly suitable matrix former in controlled release tablets [5,19,23,35,37]. The drug release from the matrix tablets is increased by the addition of watersoluble excipients such as lactose, in contrast to preparations containing the water-insoluble calcium phosphate [23].…”

“…The amount of the released PAP during the release study from the tablets depended on the composition of excipients contained in the formulas. Kollidon SR is a substance typically used for prolonged release solid dosage forms [5,19,23,35,37]. Four series of tablets contain the addition of Kollidon SR in amounts of 40% and 25% in T4-T6 and T7, respectively, but the obtained release profiles of P�P were different.…”

Design and <i>In Vitro</i> Evaluation of Eudragit-Based Extended Release Diltiazem Microspheres for Once- and Twice-Daily Administration: The Effect of Coating on Drug Release Behavior

“…A characteristic endotherm appeared for the drug at the onset temperature of 210.08°C, which could be attributed to the melting of DL. 27 A broad peak in the range of 50-60°C was observed in the thermogram of Eud RL, which is related to its glass transition temperature. 28 The DSC curve obtained for the microspheres presented the same thermal profile as that of the physical mixture, both containing a drug melting peak with a slight shift toward lower temperatures.…”

Design and in vitro evaluation of Eudragit-based extended release diltiazem microspheres for once and twice daily administrations: the effect of coating on drug release behavior

“…A characteristic endotherm appeared for the drug at the onset temperature of 210.08 o C which could be attributed to the melting of DL. 27 A broad peak in the range of 50-60 o C was observed in the thermogram of Eud RL which is related to its glass transition temperature. 28 The DSC curve obtained for the microspheres presented the same thermal profile as that of physical mixture, both containing the drug melting peak with a slight shift toward lower temperatures.…”