The development of materials for the controlled-release is a key area in pharmaceutical science. However, finding novel materials and determining how effective they might be used in tablet or capsule formulation is time consuming. Now, Finnish researchers have applied multivariate analysis to one such material to evaluate its potential as well as to demonstrate how this technique can be used in the excipient discovery process.

Ossi Korhonen and Jarkko Ketolainen of the Department of Pharmaceutics at the University of Kuopio, in Finland, and Sanni Matero and Antti Poso in the Department of Pharmaceutical Chemistry studied starch acetate as a matrix material for controlled-release tablets. Their statistical analysis showed that this material works well for various drugs.

Starch acetate was developed as a novel hydrophobic polymer for direct compression with the aim of endowing tablets with the ability to control the release of a drug so that there is no dosage spike and patients ingest a steady rate of drug as required. Despite its early promise, only a few researchers have published details of how effective starch acetate might be for different drugs. The Finnish team point out that because it is hydrophobic, starch acetate does not swell or dissolve in water, so drug molecules diffuse out from the tablet through water-filled pores. This, they suggest implies that the kinetics of drug release from starch acetate is diffusion-controlled, but other mechanisms are possible. They turned to multivariate analysis to help them obtain a clearer picture of drug release from this material.

They explain a multivariate approach is probably essential as drug release depends on many variables, including the drug's physicochemical properties, the nature of the excipient, and the structure of the tablet matrix. The team used drug properties described by VolSurf parameters to model the effects of significant variables on drug release. They carried out dissolution studies on nine different formulations with six different model drugs - propranolol hydrochloride, diltiatzem hydrochloride, anhydrous theophylline, ibuprofen, atenolol, and diclofenac sodium - and applied partial least squares projection of latent structures PLS analysis to evaluate the predominant properties involved in drug release.

Their study shows that starch acetate is indeed capable of acting as a controlled-release material for a range of drugs. They found that during the "burst" effect of dissolution, the tablet formulation and process variables had the most effect on drug release and subsequently the physicochemical properties of the drug molecules themselves as they pour out through the water-filled channels.

Related links:

• J Pharm Sci. 2005 Dec;94(12):2716-2730
• Poso Page
• Matero Page
• Ketolainen Page

• Korhonen page 

Article by David Bradley