DRUG-RELEASE FROM HYDROPHILIC MATRICES .1. NEW SCALING LAWS FOR PREDICTING POLYMER AND DRUG-RELEASE BASED ON THE POLYMER DISENTANGLEMENT CONCENTRATION AND THE DIFFUSION LAYER

Two scaling laws for predicting polymer and drug release profiles from hydrophilic matrices were developed. They were developed on the basis of the diffusion layer and the polymer disentanglement concentration, rho(p,dis), the critical polymer concentration below which polymer chains detach off a gelled matrix that is undergoing simultaneous swelling and dissolution. The relation between rho(p,dis) and molecular weight, M, for (hydroxypropyl)methylcellulose (HPMC) in water was established as rho(p,dis) (g/mL) proportional to M(-0.8). This power-law relationship for rho(p,dis), along with the diffusion layer adjacent to the gelled matrix, leads to the scaling law of m(p)(t)/m(p)(infinity) proportional to M(eq)(-1.15), where m(p)(t)/m(p)(infinity) is the fractional HPMC release. The scaling law explains the observation that polymer and drug release rates decreased sharply with M at low M and approach limiting values at high M. Experimentally, m(p)(t)/m(p)(infinity) was found to scale with M(eq) as m(p)(t)/m(p)(infinity) proportional to M(eq)(-0.93), where M(eq) is the equivalent matrix molecular weight. Moreover, fractional drug release, m(d)(t)/m(d)(infinity), followed M(eq) as m(d)(t)/m(d)(infinity) proportional to M(eq)(-0.48). These two scaling laws imply that, if the release profiles are known for one composition, release profiles for other compositions can be predicted. The above two power laws lead to two master curves for m(p)(t)/m(p)(infinity) and m(d)(t)/m(d)(infinity), suggesting that the release mechanism for soluble drugs from HPMC matrices is independent of matrix compositions, presumably via a diffusion-controlled process. Limitations of the power laws are discussed.