Effects of Formulation Variables and Post-compression Curing on Drug Release from a New Sustained-Release Matrix Material: Polyvinylacetate-Povidone

Abstract

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Preparation and In-vivo Pharmacokinetic Study of a Novel Extended Release Compression Coated Tablets of Fenoterol Hydrobromide

“…The kinetic data of fenoterol release from its matrix tablets F1 to F7 adopting Kollidon ® SR (Table III) shows that all formulas have a release exponent value (n) less than 0.45 indicating a Fickian (diffusion) release kinetics. This results support the diffusion mechanisms of Kollidon ® SR proposed by both BASF technical information and Shao et al (3).…”

“…Kollidon ® SR is one of the promising release retarding polymers. It has already been used to delay the release of highly water soluble drugs such as Propranolol HCl and Diphenhydramine HCl (2,3). It shows excellent flowability and can be used as an excipient for direct compression.…”

Effects of Release Modifier and Annealing on Polyvinyl Acetate-Polyvinyl Pyrrolidone Microspheres Containing Diclofenac Sodium

“…When used in the tablet formation, it undergoes little cured during the normal processing conditions and, therefore, affects physical integrity and drug release rate. 11,14 Shao et al also reported that curing after compression is very critical in stabilizing the release Figure 6. SEM photograph of batch P15 after curing.…”

“…14 Thus, in order to get a stabilized dissolution pattern of DS and improved physical stability, microspheres were subjected to curing at 60°C for 24…”

“…KSR is a water insoluble polymer and has been used in preparation of sustained release tablets, pellets, and granules. [11][12][13][14] But in this study, KSR was used as the wall material to prepare sustained release microspheres of DS as it has been shown that KSR can also be a good polymer to be used for such purpose. 15,16 Annealing is a good technique to control the release of drugs from different types of dosage forms.…”