Hildebrand solubility parameter to predict drug release from hydroxypropyl methylcellulose gels

An equation including the Hildebrand solubility parameter δ of the drugs is used for the first time to model drug release from hydroxypropyl methylcellulose (HPMC) gels: l nM = -21.578 + 2.102 δ-0.037 δ(2)+0.48 ln t + 1.028 ln C(i) (r(2) = 0.94 for a total of 286 cases). The experimentally determined release data of six drugs having different polarity (caffeine, theophylline, paracetamol, salicylic acid, naproxen and diclofenac) at several initial concentrations C(i) were included in the equation. In general, the amount of drug delivered is linear at the first 5-6h of the release profiles and the zero order constants K(o) increase as the solubility parameter of the drugs become larger. The Peppas exponential law M/M(∞) = Kt(n) is applicable to larger fractional release, until 67-87% (48-51 h) for the less polar drugs (diclofenac and naproxen, lower δ values) and more than 80% (26-28 h) for the more polar drugs (higher δ values, theophylline, salicylic acid, caffeine and paracetamol). The Peppas release rate (lnK) shows a parabolic relationship with the drug solubility parameter. The diffusional exponent n varies between 0.40 and 0.58 indicating that drug release is mainly controlled by diffusion. An extended form of the Peppas equation is also tested for each drug including all the initial concentrations: lnM = a + b ln t + c ln C(i) (r(2) = 0.88-0.94). The logarithm of the octanol-water partition coefficients can also be used in combination with the drug concentrations.