Michael Kopcha

Evaluation of release from selected thermosoftening vehicles

Abstract— Release of D&C Yellow No. 10 and anhydrous theophylline have been determined from a thermosoftening, hydrophilic matrix, Gelucire 50/13, incorporating a water‐soluble additive, polyethylene glycol 4000. As additive level increased, release also increased. The effect of mixtures of Gelucire 50/13 (G50/13) and Gelucire 50/02 (G50/02) on release was also investigated as a function of temperature and pH. As the level of G50/02 increased, release decreased and became predominantly diffusional. As temperature was increased, release changed from diffusion to a mixed model of both diffusion and erosion. At basic pH, release from these composite systems became more erosional in character, possibly reflecting partial hydrolysis of the ester‐linked matrices. Diffusion coefficients and apparent diffusion coefficients were calculated in G50/02 and G50/13 matrices, respectively, and were in agreement with published data.

Evaluation of methodology for assessing release characteristics of thermosoftening vehicles

Abstract— Methodology has been devised for the testing and evaluation of the mechanistic release of drug or markers from thermosoftening materials, as represented by the Gelucire class of excipients, which could be predictive. Release of a drug (anhydrous theophylline) and a marker (D&C yellow No. 10) was determined using a calibrated stationary disc/rotating fluid system. Of the fourteen commercially available Gelucire excipients, six were investigated in detail (G46/07, G48/09, G50/02, G50/13, G53/10, G62/05) and found to have biphasic release profiles. Lipid soluble materials demonstrated predominantly diffusion‐controlled release, while water‐dispersible materials absorbed water and showed signs of swelling which led to erosion as an additional component of the release characteristics.

Effect of Physical and Chemical Properties on Drug Release From Selected Thermosoftening Vehicles

Abstract— The release profile of several drugs, (chlorpheniramine maleate, salicylic acid, hydrochlorothiazide, p‐hydroxy benzoic acid, sulphafurazole, anhydrous theophylline) and the marker (D&C yellow No. 10) was detailed to determine the effect of physical and chemical properties on release from selected thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug or marker of 2·5% w/w, hydrochlorothiazide showed the slowest release from G50/02, due to its low aqueous solubility, while theophylline showed the highest release owing to its low mol. wt and moderate aqueous solubility. Release reflected two of the selection criteria, aqueous solubility and mol. wt, set forth for the drug/markers used in the study. The hydrophobic matrix, G50/02, offered no enhancement in drug release and functioned in a manner commensurate with other hydrophobic matrices. No hydrogen bonding was noted between any of the drugs or markers and the matrix. As drug or marker concentration increased from 2·5 to 15% w/w, potential hydrogen bonding was noted between p‐hydroxy benzoic acid and the matrix. Theophylline no longer had the highest release being replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire excipient G50/13, chlorpheniramine maleate showed the highest release; it dissolved within the matrix at experimental temperature and lowered the matrix melting point. The matrix swelled upon exposure to the dissolution medium and it was from this swollen layer that release occurred. Sulphafurazole, hydrochlorothiazide, salicylic acid and p‐hydroxy benzoic acid exerted a similar effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was observed between the drugs and matrix. As drug or marker concentration was further increased, chlorpheniramine maleate and D&C yellow No. 10 demonstrated the highest release; all other drugs formed a cluster. Apparent diffusion coefficients for G50/02 and G50/13 matrices were in agreement with published data confirming the predictive ability of the experimental design and postulated mechanistic models of release from hydrophilic and lipophilic matrices.